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Fasting produces antidepressant-like effects via activating mammalian target of rapamycin complex 1 signaling pathway in ovariectomized mice
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作者 Zi-Qian Cheng Jie Fan +4 位作者 Fang-Yi Zhao Jing-Yun Su Qi-Han Sun Ran-Ji Cui Bing-Jin Li 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第9期2075-2081,共7页
Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test.Howeve r,whether 9-hour fasting has therapeutic effects in female mice with depressive symptom... Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test.Howeve r,whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established.Therefore,in this study,we simulated perimenopausal depression via an ovariectomy in mice,and subjected them to a single 9-hour fasting 7 days later.We found that the ovariectomy increased the time spent immobile in the forced swimming test,inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefro ntal cortex,and decreased the density of dendritic spines in the hippocampus.The 9-hour acute fasting alleviated the above-mentioned phenomena.Furthermore,all of the antidepressant-like effects of 9-hour fasting were reve rsed by an inhibitor of the mammalian to rget of rapamycin complex 1.Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting.These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus.Thus,fasting may be a potential treatment for depression. 展开更多
关键词 ANTIDEPRESSANT brain-derived neurotrophic factor dendritic spine FASTING hippocampus LTP mTOR complex 1 neural plasticity ovariectomized mice RAPAMYCIN
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马钱子苷通过肠道菌群和神经肽抑制OVX小鼠骨量丢失的机制探讨
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作者 谢佑红 周天宇 +5 位作者 王金枝 王姜俨 周怡琳 唐琳 董群伟 孙平 《中国骨质疏松杂志》 CAS CSCD 北大核心 2024年第4期538-545,共8页
目的观察马钱子苷(Loganin)干预去卵巢(OVX)小鼠骨量、肠道菌群及神经肽的变化。方法28只雌性C57BL/6J小鼠随机分为假手术组(SHAM)、OVX组、Loganin低剂量组(Loganin-L)和Loganin高剂量组(Loganin-H),每组7只。Loganin-L组和Loganin-H组... 目的观察马钱子苷(Loganin)干预去卵巢(OVX)小鼠骨量、肠道菌群及神经肽的变化。方法28只雌性C57BL/6J小鼠随机分为假手术组(SHAM)、OVX组、Loganin低剂量组(Loganin-L)和Loganin高剂量组(Loganin-H),每组7只。Loganin-L组和Loganin-H组在OVX基础上分别予Loganin 5 mg/(kg·d)和20 mg/(kg·d)灌胃,SHAM组和OVX组灌胃等量蒸馏水,每日1次,持续12周。实验结束后处死取材,Micro-CT检测左侧股骨BMD、BV/TV、Tb.N及Tb.Sp;ELISA法检测血清中CTX、TRAP、P1NP、TNF-α、IL-6、IL-10、LPS、CGRP、SP、VIP、NPY水平;16 S rRNA高通量测序技术检测粪便中肠道菌群多样性与差异性。结果OVX组BMD、BV/TV、Tb.N、P1NP、IL-10、CGRP、SP、VIP、NPY较SHAM组显著降低(P<0.05,P<0.01),Tb.Sp、CTX、TRAP、TNF-α、IL-6、LPS显著增高(P<0.05,P<0.01)。Loganin-L组BMD、BV/TV、Tb.N、P1NP、IL-10、CGRP、SP、VIP、NPY较OVX组有升高趋势(P>0.05),Tb.Sp、CTX、TRAP、TNF-α、IL-6、LPS有降低趋势(P>0.05)。Loganin-H组BMD、BV/TV、Tb.N、P1NP、IL-10、CGRP、SP、VIP、NPY较OVX组显著增高(P<0.05),Tb.Sp、CTX、TRAP、TNF-α、IL-6、LPS显著降低(P<0.05)。在门水平,与SHAM组相比,OVX组Firmicutes/Bacteroidota(F/B)率显著降低(P<0.05),Loganin-L组F/B率较OVX组有升高趋势(P>0.05),Loganin-H组F/B率显著升高(P<0.05);在属水平,OVX组norank-f_Muribaculaceae丰度较SHAM组显著增加(P<0.05),Lactobacillus丰度显著减少(P<0.05);较OVX组,Loganin-L组norank-f_Muribaculaceae丰度有降低趋势(P>0.05),Lactobacillus丰度有升高趋势(P>0.05),Loganin-H组norank-f_Muribaculaceae丰度显著减少(P<0.05),Lactobacillus丰度显著增加(P<0.01)。结论Loganin呈剂量依赖性抑制OVX小鼠骨量丢失,其机制可能是通过调节肠道菌群中norank-f_Muribaculaceae和Lactobacillus丰度、增加神经肽含量及降低炎症反应实现的。 展开更多
关键词 中医中药 马钱子苷 去卵巢小鼠 骨质疏松
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Effects of genistein on neuronal apoptosis,and expression of Bcl-2 and Bax proteins in the hippocampus of ovariectomized rats 被引量:6
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作者 Yun Peng Bo Jiang +2 位作者 Huiling Wu Ruchun Dai Liming Tan 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第36期2874-2881,共8页
Genistein is one of several isoflavones that has a structure similar to 17β-estradiol, has a strong antioxidant effect, and a high affinity to estrogen receptors. At 15 weeks after ovariectomy, the expression of Bcl-... Genistein is one of several isoflavones that has a structure similar to 17β-estradiol, has a strong antioxidant effect, and a high affinity to estrogen receptors. At 15 weeks after ovariectomy, the expression of Bcl-2 in the hippocampus of rats decreased and Bax expression increased, with an obvious upregulation of apoptosis. However, intraperitoneal injection of genistein or 17β-estradiol for 15 consecutive weeks from the second day after operation upregulated Bcl-2 protein expression downregulated Bax protein expression, and attenuated hippocampal neuron apoptosis. Our experimental findings indicate that long-term intervention with genistein can lead to a decrease in apoptosis in hippocampal neurons following ovadectomy, upregulate the expression of Bcl-2, and downregulate the expression of Bax. In addition, genistein and 17β-estradiol play equal anti-apoptotic and neuroprotective roles. 展开更多
关键词 ovariectomized model rats HIPPOCAMPUS apoptosis BCL-2 BAX GENISTEIN 17Β-ESTRADIOL braininjury neural regeneration
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Activities of the Deriviatives of Chitin on the Osbeoblast Proliferation and the Effect on Bone Strength in Ovariectomized Rats 被引量:5
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作者 WEI Changzheng LIU Wanshun +1 位作者 HAN Baoqin DUAN Yixiang 《Wuhan University Journal of Natural Sciences》 CAS 2006年第3期715-719,共5页
This study intends to examine the effects of different concentrations of four kinds of degradations of chitin: glucosamine (GLC), N-acetyl-D-glucosamine (NAG), chitooligosaccharide(COS), CM-chitooligosaccharide... This study intends to examine the effects of different concentrations of four kinds of degradations of chitin: glucosamine (GLC), N-acetyl-D-glucosamine (NAG), chitooligosaccharide(COS), CM-chitooligosaccharide (CM-COS)—on the proliferation of MC3T3-E1 cell line cultured in vitro. Results suggest that all of the glucoses mentioned above promoted the proliferation of osteoblast, and various concentrations have different effects: the proliferation was remarkable when the concentration of GLC, NAG, COS, CM-COS was 100 , 100, 500, 500 μg/mL ,respectively. Furthermore we choose the glucosamine as the material and study the effect on the bone strength in ovariectomized rats. The results showed that the middle does of glucosamine can significantly increase the hone strength of femur in ovariectomized rats. 展开更多
关键词 GLUCOSAMINE CHITIN ovariectomized rats bone strength OSTEOPOROSIS osteohlast proliferation
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The Effect of Estrogen on the Restoration of Bone Mass and Bone Quality in Ovariectomized Rats 被引量:3
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作者 陈璐璐 曾天舒 +2 位作者 夏文芳 黎惠青 周愍 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2000年第4期283-286,共4页
To evaluate the effect of estrogen on its ability to restore the bone mass and bone quality in ovariectomized rats by examining the changes of bone morphology and histomorphometry, 3- month-old rats were divided rand... To evaluate the effect of estrogen on its ability to restore the bone mass and bone quality in ovariectomized rats by examining the changes of bone morphology and histomorphometry, 3- month-old rats were divided randomly into 4 groups: normal control, ovariectomized (OVX), sham- operated (Sham-O) and OVX plus estrogen (OVX+E2). Treatment initiated from the day 8 weeks after operation and continued for 12 weeks. Bone morphology and histomorphometry were examined afterwards. Results showed that comparing to control group, the trabecular bone in OVX appeared thinner and reduced in the amount. The connectivity between trabecula was decreased and the struc- ture disordered. The free-end of trabecula was increased. The cavity of bone marrow enlarged. After treatment with estrogen, above changes improved remarkably by different degree, although did not reach the normal face. The bone histomorphometry results damonstrated that estrogen treatment in- creased bone mass and the amount of trabecula by 129% and 132% respectively (P<0. 05). The activity of bone resorption decreased significantly and the rate of bone formation increased to 203%. These results suggest that treatment of ovariectomized rats with estrogen can not only increase bone mass, also improve the bone structure and enhance the property of bone mechanics. 展开更多
关键词 ESTROGEN ovariectomized rats MORPHOLOGY HISTOMORPHOMETRY OSTEOPOROSIS
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Effects of Radix Puerariae flavones on liver lipid metabolism in ovariectomized rats 被引量:18
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作者 Ji-FengWang Yan-XiaGuo Jan-ZhaoNiu JuanLiu Ling-QiaoWang Pei-HengLi 《World Journal of Gastroenterology》 SCIE CAS CSCD 2004年第13期1967-1970,共4页
AIM: To study the effects of Radix Puerariae flavones (RPF) on liver lipid metabolism in ovariectomized (OVX) rats.METHODS: Forty adult female Wistar rats were randomly divided into four groups: OVX group; sham-OVX gr... AIM: To study the effects of Radix Puerariae flavones (RPF) on liver lipid metabolism in ovariectomized (OVX) rats.METHODS: Forty adult female Wistar rats were randomly divided into four groups: OVX group; sham-OVX group;OVX+estrogen group and OVX+RPF group. One week after operation rats of the first two groups were treated with physiological saline, rats of OVX+estrogen group with estrogen (1 mg/kg.b.w.) and rats of OVX+RPF group with RPF (100 mg/kg.b.w.), respectively for 5 weeks. After the rats were killed, their body weight, the weight of the abdominal fat and uterus were measured, and the levels of total cholesterol (TC) and triglyceride (TG) in liver homogenate were determined.RESULTS: Compared with the sham-OVX group, the body mass of the rats in OVX group was found ino-eased significantly;more abdominal fat in store; TC and TG in liver increased and uterine became further atrophy. As a result, the RPF was found to have an inhibitive action on those changes of various degrees.CONCLUSION: RPF has estrogen-like effect on lipid metabolism in liver and adipose tissue. 展开更多
关键词 葛根类黄酮 肝脏 脂质代谢 卵巢切除术 老鼠 RPF ovx
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Bone loss prevention in ovariectomized rats using stable amorphous calcium carbonate 被引量:1
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作者 Galit Shaltiel Elad Bar-David +8 位作者 Oren E. Meiron Eitan Waltman Assaf Shechter Eliahu D. Aflalo David Stepensky Amir Berman Berdine R. Martin Connie M. Weaver Amir Sagi 《Health》 2013年第7期18-29,共12页
In assessing the relationship between calcium supplementation and maintaining bone mass or reducing the risk of fracture, the effectiveness of calcium supplementation has never been decisive. Freshwater crayfish rely ... In assessing the relationship between calcium supplementation and maintaining bone mass or reducing the risk of fracture, the effectiveness of calcium supplementation has never been decisive. Freshwater crayfish rely on amorphous calcium carbonate (ACC), an instable polymorph of calcium carbonate, as the main mineral in the exoskeleton and in the temporary storage organ, the gastrolith. Inspired by the crayfish model, we have previously shown an increase in calcium bioavailability in rats administered with synthetic stable ACC vs. crystalline calcium carbonate (CCC). The current study compared the effects of amorphous calcium derived from either gastrolith or synthetic ACC with those of crystalline calcium, found in commercial CCC or calciumcitrate supplements, in a bone loss prevention model. Rats were subjected to either sham or ovariectomy (OVX) operation (n^20/ group) followed by administration of food pellets supplemented with 0.5% calcium from either source over 12 weeks. Micro-computed tomography (μCT) and histomorphometric analyses revealed bone loss prevention by both gastrolith and ACC treatments, manifested by an increase in morphometric bone parameters, compared to both CCC-?and calcium citrate-treated groups. Both gastrolith and ACC treatments resulted in bone formation in the tibia cancellous bone, indicated by dynamic histomorphometry parameters, compared to either the CCC or calcium citrate treatments. Levels of urine deoxypyridinoline (DPD), suggested an anti-resorptive effect of ACC, which was also the only treatment that led to a significant increase in vertebral mechanical strength, as supported by μCT analysis of topology and orientation parameters of the vertebral trabeculae. To our knowledge, such levels of bone loss prevention by calcium supplements have never been reported. These findings thus suggest the potential of both natural (crayfish gastrolith) and, to a greater extent, synthetic ACC sources for the prevention of metabolic bone disorders and possibly of osteoporotic processes. 展开更多
关键词 AMORPHOUS CALCIUM CARBONATE Bone Metabolism CALCIUM CARBONATE CALCIUM CITRATE Gastrolith OSTEOPOROSIS ovariectomized Rats
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Effect of Soy Isoflavone Crude Extract Supplementation on High Fat Diet-induced Insulin Resistance in Ovariectomized Rats 被引量:6
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作者 ZHANG Yun Bo LI Li Na +5 位作者 ZHAO Xin Yu CHEN Wen Hua GUO Jing Jing FU Zheng Hai YANG Yang NA Xiao Lin 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2014年第1期49-51,共3页
Female Wister rats aged 8 weeks were randomly divided into sham operation group, ovariectomized (OVX) control group, and 20VX groups fed with soy isoflavone crude extract supplementation. The rats had free access to... Female Wister rats aged 8 weeks were randomly divided into sham operation group, ovariectomized (OVX) control group, and 20VX groups fed with soy isoflavone crude extract supplementation. The rats had free access to high fat diet and water for 9 weeks. No significant difference was found in body weight (BW), total abdominal fat, food intake and food utilization rate between OVX control group and 20VX groups. However, the fasting blood glucose and blood lipid levels were significantly higher in 20VX groups than in OVX control group (P〈0.05). Intraperitoneal glucose tolerance test (IGTI") showed that the area under AUC was smaller in 20VX groups than in OVX control group (P〈0.05). These findings showed that soy isoflavone crude extract supplementation can improve glucose tolerance and prevent high fat diet-induced insulin resistance in ovariectomized rats. 展开更多
关键词 Effect of Soy Isoflavone Crude Extract Supplementation on High Fat Diet-induced Insulin Resistance in ovariectomized Rats THAN
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Effects of genistein and 17 beta-estradiol on hippocampal synaptophysin expression in ovariectomized rats
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作者 Ru Chen Liming Tan Bo Jiang 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第2期124-127,共4页
BACKGROUND: Phytoestrogen, derived from plants, is an estrogen-like element, and is effective and safe for estrogen replacement. OBJECTIVE: To compare the interventional effects of genistein and 17 S-estradiol on le... BACKGROUND: Phytoestrogen, derived from plants, is an estrogen-like element, and is effective and safe for estrogen replacement. OBJECTIVE: To compare the interventional effects of genistein and 17 S-estradiol on learning and memory and synaptophysin (SYN) expression in the hippocampus of ovariectomized rats.DESIGN: Randomized controlled animal study.SETTING: Department of Neurology, the Third Affiliated Hospital, Xiangya Medical College, Central South University. MATERIALS: 130 healthy female Sprague Dawley (SD) rats, 6 months old and weighing (293.1 ± 10.2) g, were provided by the Second Xiangya Hospital of Central South University. This animal experiment received confirmed consent from the local ethics committee. All rats were randomly divided into 5 groups, including baseline group (n= 10), sham operation group (n = 30), ovariectomized group (n = 30), genistein group (n = 30), and 17 β -estradiol group (n = 30). Rats in the latter four groups were observed for 3 weeks (n = 10) and for 15 weeks (n = 20) after model establishment. METHODS: This study was performed at the Department of Endocrinology, the Second Affiliated Hospital, Xiangya Medical College, Central South University from August 2005 to January 2006. Animals were not submitted to any treatment in the baseline group, but anesthetized and sacrificed at the 7 months of age. After anesthesia in the ovariectomized, genistein, and 17 S-estradiol groups, both ovaries were separated and resected to establish an ovariectomized model. The same volume of fat was resected in the sham operation group. After surgery, rats were intraperitoneally injected with 5 mg/kg genistein in the genistein group,10μg/kg 17 β -estradiol in the 17 β-estradiol group, and 0.1 mL/100 g dimethyl sulfoxide (DMSO)/polyethylene glycol (PEG)-200 stock solution in the sham operation and ovariectomized groups once a day until one day before sacrifice. MAIN OUTCOME MEASURES:① Learning and memory changes of SD rats were detected using water maze behavioral testing 3 and 15 weeks after surgery. ② SYN expression in the hippocampus was measured using immunohistochemistry. RESULTS: A total of 16 out of 130 rats died due to infection, and 114 rats were included in the final analysis. ① Comparison of water maze results from the five groups: by 3 and 15 weeks after surgery, escape latency was prolonged and platform-crossing times decreased in the ovariectomized group compared to the baseline, genistein, 17 β-estradiol, and sham operation groups (t = 4.17 14.64, P 〈 0.05). However, there were no significant differences in escape latency and platform-crossing times among the sham operation, genistein, and 17 S-estradiol groups (P 〉 0.05). ② Distribution and quantity of SYN immunoreactive products in hippocampus: SYN-immunoreactive cells stained darkly in the baseline and sham operation groups, but were lightly stained in the genistein, 17 S -estradiol, and ovariectomized groups. In particular, SYN-immunoreactive cells stained lightly in the ovariectomized group 15 weeks after surgery. SYN correction gray values in hippocampal sub-regions, especially in the mossy fiber layer of the CA3 region, of the ovariectomized group was lower compared to the baseline, sham operation, 17 β -estradiol, and genistein groups (t = 12.57 23.92, P 〈 0.05) 15 weeks after surgery. However, there were no significant differences in SYN correction gray values among the baseline, sham operation, 17 β -estradiol and genistein groups (P 〉 0.05). CONCLUSION: Genistein or 17 β -estradiol supplemental therapy antagonizes memory deterioration, due to endogenous estrogen deficiency and blocks the decrease of SYN expression in the hippocampus. The effect of genistein is similar to 17 β -estradiol. 展开更多
关键词 ovariectomized GENISTEIN SYNAPTOPHYSIN HIPPOCAMPUS Alzheimer's disease
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Dynamic changes of beta-amyloid protein deposition in hippocampus of female ovariectomized rats
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作者 Huiqing Xie Jianda Zhou +3 位作者 Shaodan Sun Xuhong Li Liming Deng Fengmei Li 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第1期10-13,共4页
BACKGROUND: To evaluate and summarize the effects of cerebral perfusion and vascular reserve on the treatment of SICAS. Recently, research on β-amyloid protein has focused on the regulatory effects of estrogen or ph... BACKGROUND: To evaluate and summarize the effects of cerebral perfusion and vascular reserve on the treatment of SICAS. Recently, research on β-amyloid protein has focused on the regulatory effects of estrogen or phytoestrogen on its deposition. However, there have been only a few reports on dynamic changes of β -amyloid protein deposition in hippocampus of ovariectomized rats. OBJECTIVE: To measure β -amyloid protein deposition in the hippocampal formation of ovariectomized rats by using immunohistochemistry; to observe time-dependent dynamic changes. DESIGN: Randomized controlled animal study. SETTING: Third Xiangya Hospital of Central South University. MATERIALS: The experiment was carried out in the Central Laboratory of the Third Xiangya Hospital of Central South University from November 2005 to December 2006. Fifty healthy female Sprague Dawley (SD) rats, weighing (293 ± 10) g, were provided by the Animal Laboratory of Xiangya Medical College, Central South University. All rats had neither a childbearing history nor hepatic or renal disease, or skeletal deformity. β-amyloid protein immunohistochemical kit was provided by Wuhan Boster Company. The experiment was in accordance with animal ethics standards. METHODS: All rats were randomly divided into five groups, including normal control group (n = 10), sham operation group (n = 10), and ovariectomized group (n = 30). After anesthesia in the ovariectomized group, the bilateral ovaries were separated and resected. The same volume of fat was resected in the sham operation group. Rats from the normal control group, however, did not receive any surgical treatments. Rats in the normal control group and sham operation group were sacrificed by anesthesia 7 weeks after surgery. Every ten rats from the ovariectomized group was respectively sacrificed at 7, 15, and 30 weeks after surgery. lmmunohistochemistry was used to detect β-amyloid protein deposition in hippocampal sections. Cell counting and gray value measurements served to record the dynamic changes in β-amyloid protein deposition. MAIN OUTCOME MEASURES: (1) Morphological changes. (2) Positive cell counts from β -amyloid protein stainings and gray value measurements. RESULTS: All 50 rats were involved in the final analysis. (1) Morphological changes. β -amyloid-positive cells were detected in the hippocampus of all rats. Biebrich scarlet stained neurites with a swollen cytoplasm. A few β -amyloid-positive cells were observed in all groups 7 weeks after surgery, and plasma and neurites were slightly stained. By 15 weeks after surgery, a number of β -amyloid-positive cells were observed in the ovariectomized group, and plasma and neurites were also slightly stained. By 30 weeks after surgery, however, many β-amyloid-positive cells were observed in the ovariectomized group. These cells were partially aggregated and darkly stained. (2) Positive cell counts and gray value of β-amyloid protein in hippocampus. At 7 weeks after surgery, cell counts and gray value measurements were not significantly different in the ovariectomized group compared to the sham operation group and normal control group (P 〉 0.05). Cell counts and gray value measurements were higher in the ovariectomized group by 15 weeks compared to those by 7 weeks in the normal control group, sham operation group and ovariectomized group (P 〈 0.05). At 30 weeks after surgery, cell counts and gray value measurements were higher in the ovariectomized group compared to the normal control group. In addition, there were significant differences between sham operation group and ovariectomized group, at 7 and 15 weeks after operation (P 〈 0.05-0.01 ). Cell counts and gray value measurements increased in all groups over time. CONCLUSION: Extended estrogen deficiency in rats can increase β-amyloid protein deposition in the hippocampus and the deposition increases over time. 展开更多
关键词 ovariectomized ESTROGEN rat HIPPOCAMPUS β-amyloid protein
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Effects of Orexin A on mRNA Expression of Various Neuropeptides in the Hypothalamus and Pituitary, and on Serum LH Levels in Ovariectomized Gilts
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作者 NING Hong-mei GE Ya-ming +4 位作者 SU Juan ZHANG Wen-long YAO Yuan YANG Gui-hong LEI Zhi-hai 《Agricultural Sciences in China》 CAS CSCD 2010年第9期1362-1371,共10页
Orexin has several biological functions, including the regulation of reproductive endocrine signaling, which has received much attention. However, little is known about the mechanism through which orexin regulates the... Orexin has several biological functions, including the regulation of reproductive endocrine signaling, which has received much attention. However, little is known about the mechanism through which orexin regulates the levels of neuroendocrine hormones and peptides. We injected orexin A or physiological saline into the lateral ventricle of 10 ovariectomized (OVX) gilts, and determined the subsequent changes in serum luteinizing hormone (LH) concentration by using radioimmunoassay (RIA). We also examined the expression of GnRH, NPY, and POMC mRNAs in the hypothalamus and that of LH, folliclestimulating hormone (FSH), POMC, and ghrelin mRNAs in the pituitary by using semi-quantitative reverse transcription polymerase chain reaction. We found the following results: (1) Orexin A transiently promoted LH secretion; serum LH concentration started to increase at 10 min after the orexin injection, peaked at 30 min, and returned to its initial level at 1.5 h; (2) orexin A upregulated GnRH mRNA expression and downregulated NPY and POMC mRNAs expression in the hypothalamus; (3) orexin A upregulated LH and FSH mRNAs expression (FSH, P〉 0.05), but downregulated ghrelin mRNA expression in the pituitary. No significant effects were observed on the pituitary expression of FSH and POMC mRNAs. Our data suggest that orexin A regulates reproductive function by stimulating GnRH and LH release directly and indirectly via its effects on NPY, POMC and ghrelin expression. 展开更多
关键词 orexin A ovx gilt relative neuropeptides LH HYPOTHALAMUS PITUITARY
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Effects of long-term estrogen replacement therapy on beta-amyloid precursor protein and mRNA expression in ovariectomized rat hippocampus
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作者 Bo Jiang Eryuan Liao +2 位作者 Liming Tan Ruchun Dai Zhijie Xiao 《Neural Regeneration Research》 SCIE CAS CSCD 2009年第1期48-52,共5页
BACKGROUND: In vitro cultures of neural stem cells have shown that estrogen can regulate beta-amyloid precursor protein (β-APP) metabolism and reduce amyloid-beta production. OBJECTIVE: To investigate the effects... BACKGROUND: In vitro cultures of neural stem cells have shown that estrogen can regulate beta-amyloid precursor protein (β-APP) metabolism and reduce amyloid-beta production. OBJECTIVE: To investigate the effects of long-term oral administration of compound nylestriol or low-dose 17beta-estradiol on β-APP and mRNA expression in the hippocampus of ovariectomized (OVX) rats. DESIGN, TIME AND SETTING: This randomized and controlled experiment was performed at the Animal Laboratory and Laboratory of Endocrine and Metabolic Disease, Xiangya Second Hospital of Central South University between April 2003 and May 2004. MATERIALS: According to body mass, 50 six-month-old female Sprague-Dawley rats were randomly divided into five groups (n = 10 per group): normal control, sham operation, OVX model, 17beta-estradiol (Sigma, USA), and compound nylestriol tablet (Laboratory of Endocrine and Metabolic Disease, Xiangya Second Hospital of Central South University) groups. METHODS: Rats in OVX plus 17beta-estradiol and OVX plus compound nylestriol tablet groups underwent ovariectomy. On the second day after surgery, rats were intragastrically given 17beta-estradiol (100 μg/kg), once per day or compound nylestriol tablet (0.5 mg/kg) and levonorgestrel (0.15 mg/kg) every 2 days. MAIN OUTCOME MEASURES: β-APP expression in the hippocampus of OVX rats was determined using immunohistochemistry (SABC method) and β-APP mRNA expression was analyzed by in situ hybridization. The results were quantitatively analyzed using cell counting and average optical density. RESULTS: The number and optical density of β-APP-positive neurons in every subregion of the hippocampus of OVX rats was dramatically increased compared with normal and sham operation groups following 35 weeks of administration (P 〈 0.05). Levels of β-APP were decreased following oral administration of compound nylestriol or 17beta-estradiol. In situ hybridization showed that long-term estrogen deficiency and oral administration of compound nylestriol or 17beta-estradiol did not alter the number of β-APP mRNA-positive neurons. CONCLUSION: The results show that long-term estrogen deficiency results in an increase of expression of β-APP though no changes in the expression of β-APP mRNA are detected. Replacement of estrogen with low-dose 17 beta-estradiol or compound nylestriol tablet inhibits the expression of β-APP in the hippocampus to the same extent. 展开更多
关键词 ovariectomized rats compound nylestriol tablet 17beta-estradiol cerebral hippocampus beta-amyloid precursor protein
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A peptide containing the receptor binding site of insulin-like growth factor binding protein-2 enhances bone mass in ovariectomized rats
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作者 Gang Xi Christine Wai +1 位作者 Clifford J.Rosen David R.Clemmons 《Bone Research》 SCIE CAS CSCD 2018年第3期280-288,共9页
Male Igfbp2-/-mice have a significant reduction in bone mass and administration of a peptide that contains the insulin-like growth factor binding protein-2(IGFBP-2) receptor-binding domain stimulates bone formation in... Male Igfbp2-/-mice have a significant reduction in bone mass and administration of a peptide that contains the insulin-like growth factor binding protein-2(IGFBP-2) receptor-binding domain stimulates bone formation in these animals. Female Igfbp2-/-mice do not have this phenotype but following ovariectomy(OVX) lose more bone than OVX wild-type mice. This suggests that in the absence of estrogen, IGFBP-2 is required to maintain bone mass. Therefore these studies were undertaken to determine if this peptide could stimulate bone acquisition in OVX rats. OVX rats were divided into seven treatment groups: sham animals, OVX animals, OVX animals receiving a control scrambled peptide, or one of three doses of the active peptide termed PEG-HBD-1(0.7, 2,and 6 mg·kg^(-1)) and an OVX group receiving parathyroid hormone(PTH)(50 μg·kg-1 per day). The peptides were administered for8 weeks. DXA revealed a significant reduction in femoral and tibial areal bone mineral density(aBMD) after OVX, whereas treatment with the high-dose peptide increased aBMD by 6.2% ± 2.4%(P < 0.01) compared to control peptide; similar to the increase noted with PTH(5.6% ± 3.0%, P < 0.01). Similar increases were noted with two lower doses of the peptide(3.8% ± 1.5%, P < 0.05 for low dose; 3.1% ± 1.6%, P = 0.07 for middle dose). Micro CT showed that the OVX control peptide animals had reductions of 41% and64% in femoral trabecular BV/TV and trabecular number, respectively. All three doses of the peptide increased bone volume/total volume(BV/TV) significantly, while the low and middle doses increased trabecular number. Cortical BV/TV and thickness at the midshaft increased significantly with each dose of peptide(18.9% ± 9.8%, P < 0.01 and 14.2% ± 7.9%, P < 0.01 for low dose; 23.7% ±10.7%, P < 0.001 and 15.8% ± 6.1%, P < 0.001 for middle dose; 19.0% ± 6.9%, P < 0.01 and 16.2% ± 9.7%, P < 0.001 for high dose)and with PTH(25.8% ± 9.2%, P < 0.001 and 19.4% ± 8.8%, P < 0.001). Histomorphometry showed that the lowest dose of peptide stimulated BV/TV, trabecular thickness, mineral apposition rate(MAR), bone formation rate/bone surface(BFR/BS), number of osteoblasts/bone perimeter(N.ob/B.pm), and decreased osteoclast surface/bone perimeter(Oc.S/B.Pm). The highest dose stimulated each of these parameters except MAR and BFR/BS. Thus, the heparin-binding domain receptor region of IGFBP-2 accounts for its anabolic activity in bone. Importantly, this peptide enhances bone mass in estrogen-deficient animals. 展开更多
关键词 INSULIN-LIKE growth factor BINDING protein-2 ovx WILD-TYPE mice
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Effects of Lepidium sativum supplementation on growth and gonadotropins secretion in ovariectomized, estrogen-implanted rabbits
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作者 Oluwatosin V.Imade Wuraola A.Erinfolami +4 位作者 Rasheed A.Ajadi Monsuru O.Abioja Samson A.Rahman Olusiji F.Smith Oladele S.Gazal 《Asian pacific Journal of Reproduction》 2018年第4期155-160,共6页
Objective: To test the effects of dietary supplementation of Lepidium sativum (LS) seed powder on growth performance and gonadotropins secretion in ovariectomized, estradiol-implanted rabbits. Methods: Ovariectomized,... Objective: To test the effects of dietary supplementation of Lepidium sativum (LS) seed powder on growth performance and gonadotropins secretion in ovariectomized, estradiol-implanted rabbits. Methods: Ovariectomized, estradiol-implanted Chinchilla rabbits were assigned into four experimental groups: LS seed powder was included into normal rabbit chow at 0% (control), 5% (low), 7% (mid) and 10% (high) w/w. Experimental feed and water were given ad-libitum for 3 weeks. Weekly body weights and daily feed intake of rabbits were recorded. Twenty-one days post-feeding, blood samples were collected at 15-minute interval for 3 h (PeriodⅠ) after which 2.5 μg gonadotropin-releasing hormone (GnRH) was injected intravenously and the sampling continued for another hour (PeriodⅡ). Plasma was harvested and analyzed for luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by radioimmunoassay. Results: Feed intake was significantly (P<0.05) increased in LS-supplemented rabbits. However, the increase in feed intake did not result in significant body weight gain. LS seed supplementation significantly (P<0.001) increased mean plasma LH dose-dependently from the low- to the mid-LS level and then decreased LH at the high-LS level. LS supplementation increased (P<0.001) plasma FSH secretion. Injection of GnRH had no effect on plasma LH, however significantly (P<0.05) decreased overall plasma FSH secretion. Conclusions: LS seed supplementation stimulates feed intake and gonadotropins secretion in rabbits. Gonadotropins effect may be mediated through LS seeds phytosterols through the activation of estrogen receptors thereby producing agonistic effects resulting in LH and FSH secretion. The differential responses of gonadotropins to GnRH in LS-supplemented rabbits suggest differential regulation of the synthesis and secretion of these gonadotropins. 展开更多
关键词 ovariectomized RABBITS LEPIDIUM sativum GROWTH LH FSH
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The effect of Wujiadan Recipe on serum sex hormone and expression of Kiss-1, GPR54 and GnRH in arcuate nucleus of hypothalamus in ovariectomized rats
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作者 Ming-Yu Zhao Wen-Ying Niu +3 位作者 Bo Lv Zuo-Mei Wang Xin-Hui Yao Hong-Bin Xiao 《Journal of Hainan Medical University》 2020年第18期31-34,共4页
Objective:To explore the effect of wujiadan Recipe on the expression of FSH,E2 in serum and KiSS-1,GPR54,GnRH mRNA in hypothalamic arcuate nucleus tissue homogenate of ovariectomized rats,and to further explore the me... Objective:To explore the effect of wujiadan Recipe on the expression of FSH,E2 in serum and KiSS-1,GPR54,GnRH mRNA in hypothalamic arcuate nucleus tissue homogenate of ovariectomized rats,and to further explore the mechanism of wujiadan Recipe on menopausal syndrome.Methods:Sixty-four adult female rats were randomly divided into three groups:blank group,model group,Chinese medicine control group,western medicine control group,and wujiadan high,medium and low dose groups.Except for the blank group,all the other groups were ovariectomized.The rats in the normal group and the model group were given the same dose of saline once a day.One rat in the blank group died during the experiment.After 4 weeks of continuous administration,blood was collected from abdominal aorta and brain stereotaxic localization was performed to preserve the arcuate nucleus of hypothalamus.The levels of FSH and E2 in serum were detected by enzyme-linked immunosorbent assay(ELISA),and the expression of Kiss-1,GPR54 and GnRH mRNA in arcuate nucleus of hypothalamus were detected by PCR.Results:1.Compared with the blank group,FSH level in the model group was significantly higher(P<0.01),and E2 level was significantly lower(P<0.01).Compared with the model group,the level of serum E2 in the western medicine control group increased significantly(P.The serum FSH content in each group decreased,especially in the high dose group and the western medicine control group(P<0.01),and in the Chinese medicine control group,the middle dose group and the low dose group(P<0.05).Compared with the blank group,the expression of KiSS-1 mRNA,GPR54 mRNA and GnRH mRNA in the model group increased significantly(P<0.01);compared with the model group,the expression of KiSS-1 mRNA and GPR54 mRNA in the high dose group,middle dose group and Western medicine control group of wujiadan prescription decreased significantly(P<0.05).Compared with the model group,the expression of GnRH mRNA in the high dose group and the western medicine control group decreased significantly(P<0.01);the middle dose group of wujiadan decreased significantly(P<0.05).Conclusion:Wujiadan recipe can improve the serum sex hormone level of castrated rats,and reduce the over expression of KiSS-1,GPR54 and GnRH mRNA in hypothalamic arcuate nucleus of castrated rats,which may be the reproductive endocrine mechanism of wujiadan recipe in the treatment of menopausal syndrome. 展开更多
关键词 Wujiadan recipe Menopausal syndrome ovariectomized rats Sex hormone KISS-1 GPR54 GNRH
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Agnuside Reduces Visceral Adipocyte Size,Improves Insulin Sensitivity and Reverses Hepatic Steatosis in Ovariectomized Rats
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作者 Franciele Neves Moreno Eduardo Hideo Gilglioni +6 位作者 Rosangela Fernandes Garcia Naiara Cristina Lucredi Sandra Mara Ferreira Nilton Almeida Brito Marcia do Nascimento Brito Emy Luiza Ishii-Iwamoto Clairce Luzia Salgueiro-Pagadigorria 《Journal of Pharmacy and Pharmacology》 2019年第4期133-147,共15页
This study aimed to investigate the effects of agnuside(AGN),a phytoestrogen in Vitex agnus-castus,on cellular and metabolic alterations induced by ovariectomy in rats.Ovariectomized(OVX)Wistar rats were used as an an... This study aimed to investigate the effects of agnuside(AGN),a phytoestrogen in Vitex agnus-castus,on cellular and metabolic alterations induced by ovariectomy in rats.Ovariectomized(OVX)Wistar rats were used as an animal model of postmenopausal metabolic syndrome.The visceral and subcutaneous adipocyte sizes,the peripheral insulin sensitivity and the occurrence of nonalcoholic fatty liver disease(NAFLD)and liver oxidative damage were evaluated.The results were compared with those obtained from control rats(sham-operated)and OVX rats treated daily with AGN.Obese OVX rats exhibited visceral adipocyte hypertrophy and developed glucose intolerance,hyperinsulinemia,NAFLD and dyslipidemia.AGN exerted beneficial effects on several metabolic parameters in OVX rats,including the improvement in glucose intolerance,hyperinsulinemia and NAFLD.Besides,AGN promoted a general improvement in the liver redox state.Although the reduction of the mesenteric adipocyte size is very likely to be an important mode of action of AGN,some actions of AGN could also involve the interaction with estrogen receptors. 展开更多
关键词 METABOLIC syndrome ovariectomized rats ADIPOCYTE size NAFLD agnuside
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S1-5 Effects of Osthole on Learning and Memory and the Estrogen Pathway in Ovariectomized Rats
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作者 YU Li-li XU Li +5 位作者 WANG Yi-nuo XUE Lu-ning Gou Ji-wei LI Hong-bo HOU Xue-qin ZHANG Han-ting 《神经药理学报》 2018年第4期7-8,共2页
Objective:To investigate the effects of osthole,a natural coumarin first derived from the Cnidium plant,on learning and memory,physiological and pathological changes,and expression of estrogen receptor(ER)αandβin th... Objective:To investigate the effects of osthole,a natural coumarin first derived from the Cnidium plant,on learning and memory,physiological and pathological changes,and expression of estrogen receptor(ER)αandβin the brain of ovariectomized(OVX)rats of Alzheimer’s disease(AD)models.Methods:Female rats were randomly divided into six groups:①sham operation,and OVX plus:②saline,③Estradiol(0.1 mg·kg-1;positive control),④osthole at 12.5 mg·kg-1,⑤osthole at 25 mg·kg-1,and⑥osthole at 50 mg·kg-1;intragastric administration for 30 days.The Morris water-maze test was used to evaluate the learning and memory ability of rats,ELISA to measure the levels of estradiol in the serum,Western blotting to detect the expression of ERαand ERβin the hippocampus,and HE staining to determine the histopathological changes in the brain.Results:①Effects on learning and memory:compared to the OVX alone,osthole at 25 or 50 mg·kg-1 signifi cantly increased the number of entries and the duration in the target quadrant in the water-maze probe trial test(P<0.05).②Effects on the estrogen pathway in the brain:the level of estradiol in the serum and expression of ERβin the hippocampus in the OVX alone were signifi cantly lower,while the expression of ERαwas higher,relative to the sham operation control(P<0.01);osthole at 25 mg·kg-1 reversed the OVX-induced changes in expression of ERαand ERβ(P<0.01).③Effects on histopathological change in the brain:in comparison with the sham operation group,the OVX rats treated with saline displayed increases in the number of apoptotic cells in the hippocampus,which was reversed by osthole at 25 or 50 mg·kg-1(P<0.05),but not the lower dose of 12.5 mg·kg-1.Conclusion:Osthole produced enhancement of learning and memory in the ovariectomized dementia model,which was mediated,at least in part,by regulating neuronal apoptosis and the estrogen pathway.Therefore,osthole is potent in delaying the development of female neurodegenerative diseases,which provides a potential,new approach to treatment of female AD. 展开更多
关键词 OSTHOLE ESTRADIOL Alzheimer’s disease ovariectomized learning and memory
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NP-15 Effects of Biochanin A on Learning and Memory in Ovariectomized Rats
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作者 YAN Ting-ting ZHANG Xue +1 位作者 GAO Yun-sheng ZHOU Yan-meng 《神经药理学报》 2018年第4期113-114,共2页
Objective:To observe the effects of biochanin A on learning and memory of ovariectomized rats and the histopathological changes in uterus and breast tissues,so as to look for a new drug instead of estradiol to prevent... Objective:To observe the effects of biochanin A on learning and memory of ovariectomized rats and the histopathological changes in uterus and breast tissues,so as to look for a new drug instead of estradiol to prevent or treat neuro-degenerative diseases after menopause.Method:A total of 48 six-month-old female rats were randomly divided into six groups:sham group,model group,17β-estrodiol,Biochanin A high-dose group,middle-dose group and low-dose group.The changes of the spatial learning and memory function were observed through Morris water maze.After the treatment,morphous of the hippocampus were observed after HE stained by microscope.Internal structure of hippocampal neurons was observed under transmission electron microscope.Colorimetry method was used to test SOD and GSH-PX activity and MDA content in the left cerebral homogenate.Western Blot was used to examine the expression of PPAR gamma and MMP-2 in right hippocampus of rats.After the treatment,the histopathological changes in uterus and breast tissues were observed to probe its safety for therapy.Result:Biochanin A could significantly antagonize the decrease of spatial learning and memory induced by OVX.Under the optical microscope and Electron microscopy observation,The number of necrosis nerve cells in Biochanin A treatment groups were significantly reduced.Biochanin A groups could decrease the content of MDA,and increase the activity of GSH-PX,SOD.The expression of PPAR gamma was down regulated and the expression of MMP-2 was up regulated in Biochanin A groups.The number of acini decreased,tissue atrophy in model group,low-dose group and middle-dose group,but the situatiion reserved in high-dose group.Conclusion:Biochanin A could significantly improve memory dysfunction due to lower estrogen levels in rats,the mechanism of which may be related to antioxidative stress. 展开更多
关键词 PHYTOESTROGEN Biochanin A AIzheimer’s disease MORRIS water MAZE ANTIOXIDATIVE stress ovariectomized RAT
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NP-21 Effects and Mechanisms of Estrogen on Endogenous Growth Hormone in Brain of Ovariectomized Rats
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作者 ZHAO Qi-xiang WANG Kai-nan +3 位作者 XU Bing-bing SU Zheng-wei HUANG Hui-zhu ZHOU Yan-meng 《神经药理学报》 2018年第4期118-119,共2页
Objective:To observe the effects of estrogen/plant estrogen(Biochanin A,BCA)on learning and memory of ovariectomized rats,so as to explore the possible mechanisms of neuroprotective effect on endogenous growth hormone... Objective:To observe the effects of estrogen/plant estrogen(Biochanin A,BCA)on learning and memory of ovariectomized rats,so as to explore the possible mechanisms of neuroprotective effect on endogenous growth hormone.Method:A total of 50 six-month-old female rats were randomly divided into five groups:sham group,model group,17β-estrodiol,Biochanin A high-dose group,and low-dose group.The changes of the spatial learning and memory function were observed through Morris water maze and shuttle box.After the treatment,morphological structures of rat neurons were observed by HE staining and electron microscopy.The contents of E2 and GH in serum were determined by ELISA and associated proteins of growth hormone JAK/STAT signaling pathway were examined by western blot.Result:Estrogen/BCA could enhance learning and memory ability of the aging rats,improve the structures of the nerve cells,increase E2,GH and IGF1 levels,improve STAT5 and p-STAT5 protein expression and reduce SOCS2 protein expression.Conclusion:Estrogen/BCA could significantly improve memory dysfunction,the mechanisms may be related to increase secretion of endogenous growth hormone,regulate growth hormone JAK/STAT signaling pathway. 展开更多
关键词 PHYTOESTROGEN biochanin A MORRIS water MAZE SHUTTLE box JAK/STAT ovariectomized rat
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河南新野产紫甘蓝花青素的提取工艺和调节双卵巢切除模型(OVX)小鼠糖耐量的研究
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作者 周自亮 张艺菁 +5 位作者 何叶 周少金 张亚丽 詹艳柯 曹红卫 张仲鸣 《安徽农业科学》 CAS 2023年第16期156-161,173,共7页
[目的]探讨新野产紫甘蓝中花青素提取的最适条件,并揭示其对更年期模型动物糖耐量的调节作用。[方法]利用紫外-可见分光光度计和Greey公式直接计算提取液中花青素光密度和含量,探讨乙醇浓度、温度、提取时间和料液比等单因素对花青素提... [目的]探讨新野产紫甘蓝中花青素提取的最适条件,并揭示其对更年期模型动物糖耐量的调节作用。[方法]利用紫外-可见分光光度计和Greey公式直接计算提取液中花青素光密度和含量,探讨乙醇浓度、温度、提取时间和料液比等单因素对花青素提取的作用,并利用正交试验获得最佳提取条件;利用双卵巢切除模型小鼠(OVX)和腹腔葡萄糖耐量试验(IPGTT)研究紫甘蓝花青素对模型小鼠糖耐量的改善作用,利用定量PCR探讨相关机理。[结果]单因素试验发现,在酸化乙醇的条件下,乙醇浓度为40%、温度为55℃、提取时间为4 h、料液比为1∶15(g∶mL)时提取效果最好;正交试验表明,提取温度70℃、乙醇浓度60%、提取时间4 h、料液比1∶20为最佳提取条件,在此条件下,1 kg紫甘蓝中可得到花青素148.8 mg。花青素灌胃[100 mg/(kg·d),0.5 mL]处理OVX小鼠70 d后,相较假手术对照组,OVX手术导致小鼠糖耐量显著降低,曲线下面积(AUC)增加37.2%(P<0.05);普通甘蓝对糖耐受的调节并不显著,紫甘蓝花青素则可使OVX动物糖耐量的AUC降低30.5%,与假手术组的基本相当。定量PCR研究发现,相对假手术组(Shm+H_(2)O),OVX手术(OVX+H_(2)O)小鼠肝脏葡萄糖-6-磷酸酶(G6Pase)的表达水平升高了(5.22±1.02)倍,OVX+花青素组(OVX+BOR)和OVX+0.02 mg/(kg·d)补佳乐(OVX+E_(2))的表达量分别升高了(2.40±0.34)和(1.82±0.18)倍,与OVX+H_(2)O和OVX+BO组相比,OVX+E_(2)组、OVX+BOR组均显著降低了肝脏中G6Pase水平。[结论]紫甘蓝是天然花青素的重要来源,其可通过降低OVX小鼠肝脏中G6Pase的表达改善糖耐量,对缓解更年期高血糖等代谢综合征有一定的价值。 展开更多
关键词 紫甘蓝 花青素 提取工艺 糖耐量 双卵巢切除模型
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