Objective:To study the effect of total flavonoids of Rhizoma Drynariae on the expression of NMDAR1,GluR2 and CAMKⅡprotein in model mice of kidney deficiency induced by exogenous glucocorticoid hydrocortisone and its ...Objective:To study the effect of total flavonoids of Rhizoma Drynariae on the expression of NMDAR1,GluR2 and CAMKⅡprotein in model mice of kidney deficiency induced by exogenous glucocorticoid hydrocortisone and its mechanism.Methods:Kunming(KM)mice were randomly divided into the blank group,the hydrocortisone model group,the anti-brain failure capsule group,the Drynaria total flavonoids group,the Drynaria total flavonoids+ER blocker group,with 15 animals in each group.Except for the blank group,all groups were injected intramuscularly with hydrocortisone(25 mg·kg^(-1)·d^(-1))to create models.The water maze experiment,new object recognition experiment and platform jump experiment were used to conduct behavioral investigations.HE staining was used to observe the pathological changes of mouse hippocampus,and Western blotting detected the expressions of NMDR1,GluR2 and CAMKⅡproteins in the hippocampus of mice in each group.Results:The experimental results showed that compared with the model group,the learning and memory ability of the mice in the Drynaria fortunei total flavonoids group was significantly improved,and the difference was statistically significant(P<0.01),the expression of NMDR1 and GluR2 proteins in the hippocampus of the mice was significantly increased(P<0.01),and the level of CAMKⅡprotein significantly decreased(P<0.01).Conclusion:The total flavonoids of Rhizoma Drynariae may enhance the expression of NMDAR1 and GluR2 protein in the brain of hydrocortisone model mice through ER,reduce the expression of CAMKⅡprotein,and alleviate the damage to the brain tissue of the model mice and play a neuroprotective effect.展开更多
目的探讨骨碎补总黄酮(total flavonoids of rhizoma drynariae,TFRD)对去卵巢(ovariectomized,OVX)骨质疏松大鼠氧化应激的影响及其机制。方法构建OVX骨质疏松大鼠模型,分别用TFRD和补佳乐(BJL)灌胃,给药12周后称重,取股骨组织和血清...目的探讨骨碎补总黄酮(total flavonoids of rhizoma drynariae,TFRD)对去卵巢(ovariectomized,OVX)骨质疏松大鼠氧化应激的影响及其机制。方法构建OVX骨质疏松大鼠模型,分别用TFRD和补佳乐(BJL)灌胃,给药12周后称重,取股骨组织和血清。HE染色观察股骨组织形态学变化,免疫组织化学染色检测股骨组织中骨保护素(osteoprotegerin,OPG)和骨形态发生蛋白2(bone morphogenetic protein 2,BMP-2)的表达,生化试剂盒检测血清中超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和活性氧(reactive oxygen species,ROS)的水平,Western blot检测股骨组织中Notch1、发状分裂相关增强子1(hairy and enhancer of split 1,Hes1)、过氧化还原酶1(peroxiredoxin 1,Prdx1)蛋白的表达。结果TFRD和BJL均能显著抑制OVX所致的大鼠体重的增加(P<0.01),并改善骨小梁的结构的完整性,缩短骨小梁间距,显著降低病理评分(P<0.01)。此外,TFRD和BJL均能升高血清SOD水平(P<0.01),降低MDA和ROS水平(P<0.01),促进股骨组织中OPG、BMP-2的表达(P<0.01),并抑制Notch1、Hes1和Prdx1蛋白的表达(P<0.01)。结论TFRD可抑制OVX大鼠的氧化应激反应,调控骨稳态,其发挥抗骨质疏松的作用可能与抑制Notch1/Hes1/Prdx1通路有关。展开更多
Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese wom...Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese women with primary osteoporosis. Methods： A total of 98 female patients from the communities of Jingshan, Beixinqiao, Jiaodaokou, Chaoyangmen, and Donghuamen in Beijing, China, aged 40 to 80 years, were included in this study. Blood samples were collected before and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after a single oral dose of Qianggu Capsule. The concentration in blood samples from 32 patients before and 0.5, 1, 2, 3, and 4 h after drug administration were determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS） method, and full set of pharmacokinetic data was analyzed with nonlinear mixed-effect modeling （NONMEM） software. The mean of population parameters clearance （C1）, central distribution volume （V）, absorption rate constant （Kal）, inter-compartmental clearance （C2）, peripheral distribution volume （V2） were set as parameters and estimated through base model, covariate model, and final model. Age, height, weight, blood urea nitrogen （BUN）, serum creatinine （Scr）, alanine transaminase （ALT）, aspartate transaminase （AST）, hyperlipidemia, Liver （Gan） Kidney （Shen） yin insufficiency （GSYI）, Kidney （Shen） yang insufficiency （SYI） were set as covariates. Results： The relationships between these parameters and covariates were analyzed. The results showed that C1 was the main parameter influenced by the selected covariates among the population parameters, and the relationships between the covariates and C1 were analyzed, among the selected covariates hyperlipidemia was identified as significant covariate of C1. Conclusion： The pharmacokinetic behaviors of naringin are altered with hyperlipidemia in Chinese women with primary osteoporosis.展开更多
目的观察骨碎补总黄酮对去卵巢大鼠核因子κB受体活化因子配体(RANKL)/骨保护素(OPG)表达及丝裂原活化蛋白激酶(MAPK)信号通路的影响。方法选用雌性大鼠45只,分为假手术组(15只)和手术组(30只),手术组行双侧卵巢切除术,造模12周时测定B...目的观察骨碎补总黄酮对去卵巢大鼠核因子κB受体活化因子配体(RANKL)/骨保护素(OPG)表达及丝裂原活化蛋白激酶(MAPK)信号通路的影响。方法选用雌性大鼠45只,分为假手术组(15只)和手术组(30只),手术组行双侧卵巢切除术,造模12周时测定BMD,确认OP复制成功后,将手术组大鼠又随机分为模型组和骨碎补总黄酮给药组,每组均15只;给药组大鼠给予骨碎补总黄酮灌胃,持续时间为12周,模型组和假手术组同时给予等量生理盐水灌胃;实验结束后测定大鼠的BMD,ELISA法检测大鼠血清RANKL、OPG含量,RT-PCR检测大鼠骨组织RANKL、OPG m RNA表达,Western blot法检测骨组织c-Jun氨基末端激酶(JNK)、p38MAPK(p38)、细胞外调节激酶(ERK)的磷酸化水平及c-Fos表达。结果干预治疗12周后:(1)与假手术组相比,模型组大鼠左、右股骨BMD降低(P<0.05),血清RANKL含量增加、OPG含量降低、RANKL-OPG比值增大(P均<0.05),骨组织RANKL m RNA表达增加、OPGm RNA表达减少(P均<0.05)。(2)与模型组比较,假手术组和骨碎补总黄酮治疗组左、右股骨BMD均增加(P均<0.05),血清RANKL含量降低、OPG含量增加、RANKL-OPG比值减小(P均<0.05),骨组织RANKL m RNA表达减少、OPG m RNA表达增加(P均<0.05),且假手术组和骨碎补总黄酮治疗组之间比较差异有统计学意义(P<0.05);(3)与模型组比较,假手术组和骨碎补总黄酮治疗组大鼠骨组织P-JNK、c-Fos表达降低(P均<0.05),但这两组间比较差异无统计学意义(P>0.05)。结论骨碎补总黄酮可增加去卵巢大鼠骨密度,其途径可能是通过调节RANKL-OPG平衡、抑制JNK磷酸化及c-Fos表达实现的。展开更多
基金General Program of National Natural Science Foundation of China(No.81673581)National Key Research and Development Program(No.2017YFC1700701)+2 种基金Scientific and Technological Achievements R&D and Cultivation Project of Heilongjiang Provincial Universities(No.TSTAU-C2018020)Research Project of Heilongjiang Provincial Health Commission(No.2020-303)Heilongjiang University of Traditional Chinese Medicine Research Fund(No.2018jkcy05,No.2018pt04,No.2019BJP01)。
文摘Objective:To study the effect of total flavonoids of Rhizoma Drynariae on the expression of NMDAR1,GluR2 and CAMKⅡprotein in model mice of kidney deficiency induced by exogenous glucocorticoid hydrocortisone and its mechanism.Methods:Kunming(KM)mice were randomly divided into the blank group,the hydrocortisone model group,the anti-brain failure capsule group,the Drynaria total flavonoids group,the Drynaria total flavonoids+ER blocker group,with 15 animals in each group.Except for the blank group,all groups were injected intramuscularly with hydrocortisone(25 mg·kg^(-1)·d^(-1))to create models.The water maze experiment,new object recognition experiment and platform jump experiment were used to conduct behavioral investigations.HE staining was used to observe the pathological changes of mouse hippocampus,and Western blotting detected the expressions of NMDR1,GluR2 and CAMKⅡproteins in the hippocampus of mice in each group.Results:The experimental results showed that compared with the model group,the learning and memory ability of the mice in the Drynaria fortunei total flavonoids group was significantly improved,and the difference was statistically significant(P<0.01),the expression of NMDR1 and GluR2 proteins in the hippocampus of the mice was significantly increased(P<0.01),and the level of CAMKⅡprotein significantly decreased(P<0.01).Conclusion:The total flavonoids of Rhizoma Drynariae may enhance the expression of NMDAR1 and GluR2 protein in the brain of hydrocortisone model mice through ER,reduce the expression of CAMKⅡprotein,and alleviate the damage to the brain tissue of the model mice and play a neuroprotective effect.
文摘目的探讨骨碎补总黄酮(total flavonoids of rhizoma drynariae,TFRD)对去卵巢(ovariectomized,OVX)骨质疏松大鼠氧化应激的影响及其机制。方法构建OVX骨质疏松大鼠模型,分别用TFRD和补佳乐(BJL)灌胃,给药12周后称重,取股骨组织和血清。HE染色观察股骨组织形态学变化,免疫组织化学染色检测股骨组织中骨保护素(osteoprotegerin,OPG)和骨形态发生蛋白2(bone morphogenetic protein 2,BMP-2)的表达,生化试剂盒检测血清中超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和活性氧(reactive oxygen species,ROS)的水平,Western blot检测股骨组织中Notch1、发状分裂相关增强子1(hairy and enhancer of split 1,Hes1)、过氧化还原酶1(peroxiredoxin 1,Prdx1)蛋白的表达。结果TFRD和BJL均能显著抑制OVX所致的大鼠体重的增加(P<0.01),并改善骨小梁的结构的完整性,缩短骨小梁间距,显著降低病理评分(P<0.01)。此外,TFRD和BJL均能升高血清SOD水平(P<0.01),降低MDA和ROS水平(P<0.01),促进股骨组织中OPG、BMP-2的表达(P<0.01),并抑制Notch1、Hes1和Prdx1蛋白的表达(P<0.01)。结论TFRD可抑制OVX大鼠的氧化应激反应,调控骨稳态,其发挥抗骨质疏松的作用可能与抑制Notch1/Hes1/Prdx1通路有关。
基金Supported by Significant Drug Research and Development in Important State Science and Technology Specific and Key Technique Research(No.2009ZX09502-030)
文摘Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese women with primary osteoporosis. Methods： A total of 98 female patients from the communities of Jingshan, Beixinqiao, Jiaodaokou, Chaoyangmen, and Donghuamen in Beijing, China, aged 40 to 80 years, were included in this study. Blood samples were collected before and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after a single oral dose of Qianggu Capsule. The concentration in blood samples from 32 patients before and 0.5, 1, 2, 3, and 4 h after drug administration were determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS） method, and full set of pharmacokinetic data was analyzed with nonlinear mixed-effect modeling （NONMEM） software. The mean of population parameters clearance （C1）, central distribution volume （V）, absorption rate constant （Kal）, inter-compartmental clearance （C2）, peripheral distribution volume （V2） were set as parameters and estimated through base model, covariate model, and final model. Age, height, weight, blood urea nitrogen （BUN）, serum creatinine （Scr）, alanine transaminase （ALT）, aspartate transaminase （AST）, hyperlipidemia, Liver （Gan） Kidney （Shen） yin insufficiency （GSYI）, Kidney （Shen） yang insufficiency （SYI） were set as covariates. Results： The relationships between these parameters and covariates were analyzed. The results showed that C1 was the main parameter influenced by the selected covariates among the population parameters, and the relationships between the covariates and C1 were analyzed, among the selected covariates hyperlipidemia was identified as significant covariate of C1. Conclusion： The pharmacokinetic behaviors of naringin are altered with hyperlipidemia in Chinese women with primary osteoporosis.
文摘目的观察骨碎补总黄酮对去卵巢大鼠核因子κB受体活化因子配体(RANKL)/骨保护素(OPG)表达及丝裂原活化蛋白激酶(MAPK)信号通路的影响。方法选用雌性大鼠45只,分为假手术组(15只)和手术组(30只),手术组行双侧卵巢切除术,造模12周时测定BMD,确认OP复制成功后,将手术组大鼠又随机分为模型组和骨碎补总黄酮给药组,每组均15只;给药组大鼠给予骨碎补总黄酮灌胃,持续时间为12周,模型组和假手术组同时给予等量生理盐水灌胃;实验结束后测定大鼠的BMD,ELISA法检测大鼠血清RANKL、OPG含量,RT-PCR检测大鼠骨组织RANKL、OPG m RNA表达,Western blot法检测骨组织c-Jun氨基末端激酶(JNK)、p38MAPK(p38)、细胞外调节激酶(ERK)的磷酸化水平及c-Fos表达。结果干预治疗12周后:(1)与假手术组相比,模型组大鼠左、右股骨BMD降低(P<0.05),血清RANKL含量增加、OPG含量降低、RANKL-OPG比值增大(P均<0.05),骨组织RANKL m RNA表达增加、OPGm RNA表达减少(P均<0.05)。(2)与模型组比较,假手术组和骨碎补总黄酮治疗组左、右股骨BMD均增加(P均<0.05),血清RANKL含量降低、OPG含量增加、RANKL-OPG比值减小(P均<0.05),骨组织RANKL m RNA表达减少、OPG m RNA表达增加(P均<0.05),且假手术组和骨碎补总黄酮治疗组之间比较差异有统计学意义(P<0.05);(3)与模型组比较,假手术组和骨碎补总黄酮治疗组大鼠骨组织P-JNK、c-Fos表达降低(P均<0.05),但这两组间比较差异无统计学意义(P>0.05)。结论骨碎补总黄酮可增加去卵巢大鼠骨密度,其途径可能是通过调节RANKL-OPG平衡、抑制JNK磷酸化及c-Fos表达实现的。
