Antidepressant-Like Effect of Tetramethylpyrazine in Mice and Rats

The aim of this study was to investigate the potential antidepressive-like effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, and its mechanism of the antidepressant-like action. Forced-swimming, tail-suspension, reserpine-induced hypothermia, akinesia and ptosis, 5-hydroxytryptophan (5-HTP)-induced head-twitch, and potentiation of noradrenaline (NE) toxicity tests, were per-formed to assess the potential antidepressant-like activity of TMP and to study the mechanism by which TMP exerts the antidepressant-like action. Intragastric (ig) administration of TMP markedly reduced the duration of immobility during forced-swimming tests and tail-supension test in rats and mice. TMP partialy reversed reserpine-induced hypothermia, ptosis and akinesia, and potentiated NE toxicity in mice, and these are similar to those of clomipramine;however, TMP did not potentiate 5-HTP-induced head-twitch response (HTR) in mice, and this is different from that of fluoxetine (FLU). The present data provide evidences that TMP possesses potent antidepressant-like activity, and it might be an adrenergic component of pharmacological activity, and its mechanism of antidepressant-like action is similar to that of clomipramine, and different from that of FLU.

Pharmacological effects of ethanol extract of Egyptian Artemisia herba-alba in rats and mice

Objective:To investigate some pharmacological effects including gastroprotective,antiinflammatory,analgesic,antipyretic and in vitro antioxidant effects of Artemisia herbaalba extract in different experimental models.Methods:Inflammation was induced in rat paw by subcutaneous injection of 1%(v/v)carrageenan solution.Writhes was induced in mice by intraperitoneal injection of 0.6%(v/v) acetic acid solution.Pyrexia was induced using Brewer's yeast suspension.Gastric lesion was induced in rats by oral administration of 99% ethanol.The anti-inflammatory,analgesic,antipyretic and gastroprotective activities of Artemisia herba-alba extract were investigated respectively.In vitro antioxidant effect was investigated using DPPH free radical.Results:The plant extract showed anti-inflammatory effect in carrageenan-induced paw edema in rats,analgesic effect against acetic acid-induced writhing,and antipyretic activity in Brewer's yeast model of pyrexia.Besides,it was shown to be a gastroprotective agent against ethanol-induced gastric ulcers.The plant also exhibited a free radical scavenging potential in an in vitro antioxidant study using DPPH.Conclusions:The results validate the use of the investigated plant in traditional medicine for different ailments.

Decursin Mediated Protection on Cisplatin-induced Nephrotoxicity in SD Rats and BDF1 Mice

Tisplatin is one of the valuable icancer agents against several types of neoplasm. However, nephrotoxicity is the major adverse effect representing in cisplatin therapy. In this study, the animal tests detecting protective effects of a natural compound, Decursin, on cisplatin-induced nephrotoxicity were examined by using in vivo model. Pretreatment Decursin 10, 20 and 40 mg · kg^-1 at 48, 24 and 6 h, and administration of a single dose of Cisplatin 5.2 mg · kg^-1. Nephrotoxicity was evaluated by serum BUN and creatinine examination. There was significant difference in body weights, serum BUN and creatinine levels of the normal group. Based on the new understanding of the protective mechanisms of cisplatin-induced nephrotocivity, new strategies can be developed to prevent renal injury or to enhance recovery after cisplatin treatment.

Temporal and Qualitative Differences in the Development of Allodynic Behaviors between Mice and Rats in a Peripheral Nerve Injury Model

The spared nerve injury (SNI) model of neuropathic pain was first developed by Decosterd and Woolf in 2000 in Sprague Dawley rats to enhance reproducibility of injury and behavioral responses resulting from a partial nerve injury. Given the differences in methodology and inconsistent behavioral data published in the SNI model of neuropathic pain in mice, and given that interspecies behavioral comparisons using the same peripheral nerve injury are presently lacking, in this study we assessed the development of mechanical and cold allodynia for five weeks in C57BL/6 mice and Sprague Dawley rats that underwent SNI. In rats and mice, the tibial and peroneal branches were ligated then severed, leaving the sural branch intact. By controlling several factors in the surgical procedure and behavioral tests, we found that rats developed and maintained strong mechanical and robust cold allodynia immediately following the injury that was maintained for the duration of the experiment (five weeks). In comparison, mice developed mechanical allodynia to a lesser magnitude which peaked at 2 weeks, but did not develop cold allodynia. We found both temporal and qualitative differences in the development of allodynic behaviors between SNI-mice and SNI-rats. Parallel analysis of interspecies differences can be exploited to reveal novel molecular players leading to divergent pain behaviors.

Research progress on depression models of different strains of rats and mice

The incidence of depression is increasing day by day,and its pathogenesis is characterized by complexity and high recurrence rate.In addition,the pathogenesis has not been elucidated.There are significant differences in the reference indicators between rat and mouse models of different strains.As the experimental modeling of depression is easily affected by gender and modelling methods,it is necessary to standardize the selection of rat and mouse strains for experimental research.Although the widely used rat and mouse models of depression can meet the research on most depression diseases,with the in-depth study of component targets of traditional Chinese medicine(TCM)and the development of diagnosis and treatment of TCM dialectics,the improvement and maturity of the depression animal model that is in line with TCM syndrome classification will have more research values for the basic research of depression in Chinese medicine.Therefore,we summarize and analyze the characteristics of different strains of rats and mice based on contemporary literature in this review,in order to provide a more powerful theoretical basis for the basic research of syndromes on TCM treatment of depression.

Differences in action potential propagation speed and axon initial segment plasticity between neurons from Sprague-Dawley rats and C57BL/6 mice

Action potentials(APs)in neurons are generated at the axon initial segment(AIS).AP dynamics,including initiation and propagation,are intimately associated with neuronal excitability and neurotransmitter release kinetics.Most learning and memory studies at the single-neuron level have relied on the use of animal models,most notably rodents.Here,we studied AP initiation and propagation in cultured hippocampal neurons from Sprague-Dawley(SD)rats and C57BL/6(C57)mice with genetically encoded voltage indicator(GEVI)-based voltage imaging.Our data showed that APs traveled bidirectionally in neurons from both species;forward-propagating APs(fpAPs)had a different speed than backpropagating APs(bpAPs).Additionally,we observed distinct AP propagation characteristics in AISs emerging from the somatic envelope compared to those originating from dendrites.Compared with rat neurons,mouse neurons exhibited higher bpAP speed and lower fpAP speed,more distally located ankyrin G(AnkG)in AISs,and longer Nav1.2 lengths in AISs.Moreover,during AIS plasticity,AnkG and Nav1.2 showed distal shifts in location and shorter lengths of labeled AISs in rat neurons;in mouse neurons,however,they showed a longer AnkG-labeled length and more distal Nav1.2 location.Our findings suggest that hippocampal neurons in SD rats and C57 mice may have different AP propagation speeds,different AnkG and Nav1.2 patterns in the AIS,and different AIS plasticity properties,indicating that comparisons between these species must be carefully considered.

N-methyl-D-aspartate (NMDA) mediates vascular relaxation via nitric oxide (NO) in rats but not in mice

Amperometric studies have indicated that substance P as well as NMDA stimulates release of NO in rat aortic rings. These data have been confirmed by functional observations of vaso-relaxant action of NMDA within noradrenaline pre-contracted aortic rings, supporting the presence of NMDA receptor in rat aortic rings. It is known that the enzyme endothelial NO synthase (eNOS) mediates vasodilatation not only in rats, but also in C57BL6 mice aortic ring, indicating that in this blood vessel NO is the endogenous endothelium-derived vasodilator. In this work, amperometry together with specifically nitrites insensitive micro-biosensors have been applied to examine the effect of NMDA and substance P upon NO release in rat and in two strains of mice aortic rings. The electrochemical data monitored demonstrate that NMDA mediates vascular relaxation via NO in rats but not in mice. These results are supported by functional data, therefore they suggest that NMDA receptors are “not responding” within these experimental conditions in mice aortic rings.

Evaluation of the Anti-inflammatory and Sedative Effects of Leaf Aqueous Extract of Withania somnifera （L.） Dunal （Solanaceae）in Rats and Mice

The use of medicinal plants in South Africa is cultural. Withania somnifera is one of the medicinal plants used to treat various ailments in the country. The plant species has been used by traditional medicine practitioners to treat inflammation and painful conditions like rheumatism. It is also known to be used as a sedative and hypnotic drug. Despite the claims, there is no information in literature to corroborate the therapeutic success of Withania somnifera in the treatment of inflammation and insomnia. The study, therefore, investigated the anti-inflammatory and central nervous system depressant activities of the leaf aqueous extract of the plant species in mice and rats. Fresh leaves of W. somnifera were collected from Kirstenbosch Botanical Gardens, South Africa, authenticated by a taxonomist and a voucher specimen （UWC 005） deposited in the University＇s Herbarium. Leaf aqueous extract was prepared using standard extraction methods. The carrageenan-induced rat paw oedema test was used to determine the anti-inflammatory effects while pentobarbitone-induced sleep and locomotor activity tests were used to evaluate the sedative effect of the plant species. Phytochemical qualitative analysis, acute toxicity and HPLC studies of the plant species were also carried out using standard methods. The phytochemical qualitative analysis carried out on the dried powdered leaves of W. somnifera showed the presence of saponins, tannins and triterpene steroids. Leaf aqueous extract of IV. somnifera （100-200 mg/kg IP） significantly prolonged pentobarbitone （40 mg/kg, i.p.）-induced sleep in mice in a dose dependant manner. Diazepam （0.5 mg/kg, i.p.） significantly prolonged pentobarbitone （40 mg/kg, i.p.）-induced sleep in mice. The doses of 100 and 200 mg/kg （i.p.） of the plant species and 0.5 mg/kg （i.p.） of diazepam significantly reduced the locomotor activity of mice. Leaf aqueous extract of the plant species （50-200 mg/kg, i.p.） significantly reduced the oedema produced by carrageenan （1%） in rats over 90 min period of testing. Indomethacin （20 mg/kg, i.p.） significantly reduced carrageenan （1%）-induced oedema in rats over 120 min period of testing. The LDs0 value obtained for the leaf aqueous extract of the plant species following inter-peritoneal injection was 1,600 mg/kg while that following oral administration was probably over 4,000 mg/kg. The HPLC finger-print of the aqueous extract showed distinct peaks at the following retention times 2.977, 3.594, 4.154, 4.406, 4.660 and 15.267 min. The results obtained show that leaf aqueous extract of W. somnifera has both sedative and anti-inflammatory effects.

Comparative study on the weight loss and lipid metabolism by tea polyphenols in diet induced obese C57BL/6J pseudo germ free and conventionalized mice

The role of gut microbiota in terms of host health is becoming increasingly important.In this study,the comparative effects of tea polyphenols(TPs)on weight loss and lipid metabolism on conventionalized mice(CVZ)and pseudo germ-free(PGF)mice(treated with antibiotics)were investigated.Our findings revealed that high fat(HF)diet considerably increased the body weight,total fat and upsurge lipid indices in CVZ mice but PGF mice were not sensitive to the effect of HF diet as CVZ mice.After the dietary administration of TP,body weight,perirenal fat and epididymal fat,liver weight,glucose(GLU)level,total chloestrol(TC level),high density lipoprotein-cholesterol(HDL-C)level significantly lowered in PGF mice as compared to CVZ mice group.However,the area of fat cells and triglyceride(TG)level were significantly increased in PGF mice.In CVZ mice,TP intervention resulted in a considerable drop in the Firmicutes/Bacteroides ratio as compared to PGF mice.The intestinal flora of PGF mice was severely reduced after antibiotic treatment,while TP administration restored intestinal diversity;the abundance of Akkermansia and Lactobacillus increased,whereas the abundance of Enterobacteriaceae and Prevotella reduced.Overall,we can assume that PGF obese mice administered with TP have less anti-obesity effects compared to obese CVZ mice.

Pathological and biochemical alterations of astrocytes in ovariectomized rats injected with D-galactose:A potential contribution to Alzheimer's disease processes

Astrocytes are implicated in the pathological changes of Alzheimer's disease. Our previous studies have demonstrated that estrogen deprivation and oxidative stress act synergistically to accelerate the progress of Alzheimer's disease. Long-term D-galactose injection combined with ovariectomy may serve as a rodent model for Alzheimer's disease. To address the potential contribution of astroglia to the Alzheimer's disease pathogenesis, we investigated pathological and biochemical alterations of astrocytes under this animal model. Ovadectomized rats injected with D-galactose for 2 weeks showed extensive localization of glial fibrillary acidic protein immunoreactive astrocytes and slightly elevated glutathione levels in the hippocampus without significant impairments in the water maze test and deficits of the cholinergic analyses, compared to the saline-injected rats. Ovariectomized rats injected with D-galactose for 6 weeks, however, exhibited degeneration of astrocytes and decreased glutathione levels in the hippocampus, accompanied with severe dysfunction of behavioral test and deficiency of cholinergic terminals. Electron microscopy further confirmed the pathological changes of astrocytes, especially in the aggregated area of synapse and brain microvessels. Consistent with degeneration of perivascular astrocytic endfeet, analysis of the horseradish peroxidase demonstrated an impairment of the blood-brain barrier permeability. These findings indicate that biochemical and pathological alterations of astrocytes may partially contribute to exacerbating neuronal deficits in the course of Alzheimer's disease. Restoring neuroprotective potential of astrocytes may be a useful therapeutic target for Alzheimer's disease and other neurodegenerative diseases.

Investigation of the metabolites of five major constituents from Berberis amurensis in normal and pseudo germ-free rats

Berberis amurensis(Berberidaceae)is a traditional Chinese medicine,which is often used to treat hypertension,inflammation,dysentery and enteritis.It contains alkaloids,mainly including berberine,berbamine,magnoflorine,jatrorrhizine and palmatine.Berberis amurensis extracts(BAEs)is often orally taken.Oral herbs might be metabolized by intestinal bacteria in the small intestine.However,the interaction between the herb and the gut microbiota is still unknown.In the current study,UPLC/Q-TOFMS/MS combined with Metabolitepilot and Peakview software was used to identify the metabolites of BAEs in anti-biotic cocktail induced pseudo germ-free rats and normal rats.As a result,a total of 46 metabolites in normal rats were detected and its main metabolic pathways include demethylation,dehydrogenation,methylation,hydroxylation,sulfation and glucuronidation.Only 29 metabolites existed in pseudo germ-free rats.Dehydrogenated metabolites(M29,M30,M34 and M36),methylated metabolites(M33,M41 and M46)and other metabolites were not detected in pseudo germ-free rats.The result implied that the intestinal bacteria have an influence on the metabolism of BAEs.Furthermore,this investigation might contribute to the understanding of the metabolism of BAEs,and further promote its clinical application.

New rat to mouse xenograft transplantation of endometrium as a model of human endometriosis

Background:Endometriosis can lead to infertility.Since there is no definitive treat-ment for endometriosis,animal modelling seems necessary to examine the possible treatments.Mouse endometrium cannot be separated for endometriosis induc-tion.In addition,transplantation of uterus into the abdominal viscera to induce endometriosis causes organ damage.In this study,we defined a new model of en-dometriosis leading to separability of endometrium and a safe anatomical region for transplantation.Methods:Forty female mice were allocated to 5 groups:1,sham;2,allograft uterus transplantation of mice to anterior abdominal wall of mice;3,allograft uterus trans-plantation of mice to mesentery of mice;4,xenograft endometrial transplantation of rat to anterior abdominal wall of mice;5,xenograft endometrial transplantation of rat to mesentery of mice.Adult female rats with a previous pregnancy experience were selected and placed in the vicinity of male rats for 2 weeks to induce estrogen secre-tion and increase endometrial thickness.Results:In the 4th group of animals,compared to sham,the peritoneal concentrations of VEGF-A,TNF-α,NO,MDA,and serum levels of CA-125 and IL-37 were increased and total body weight was decreased,while weight and size of endometrial lesions were increased significantly(P<.05).Genes expression of HOXA10 and HOXA11 were decreased significantly(P<.05)in groups 2 and 4 compared to sham.Conclusions:Xenograft transplantation of endometrium from rat to anterior abdomi-nal wall of mice can potentially mimic human endometriosis morphologically,histo-logically,and genetically.

Consistent Alterations of Human Fecal Microbes After Transplantation into Germ-free Mice

Fecal microbiota transplantation(FMT)of human fecal samples into germ-free(GF)mice is useful for establishing causal relationships between the gut microbiota and human phenotypes.However,due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms,it may not be possible to replicate human phenotypes in mice through FMT;similarly,treatments that are effective in mouse models may not be effective in humans.In this study,we aimed to identify human gut microbes that undergo significant and consistent changes(i.e.,in relative abundances)after transplantation into GF mice in multiple experimental settings.We collected 16S rDNA-seq data from four published studies and analyzed the gut microbiota profiles from 1713 human–mouse pairs.Strikingly,on average,we found that only 47%of the human gut microbes could be re-established in mice at the species level,among which more than 1/3 underwent significant changes(referred to as“variable taxa”).Most of the human gut microbes that underwent significant changes were consistent across multiple human–mouse pairs and experimental settings.Consequently,about 1/3 of human samples changed their enterotypes,i.e.,significant changes in their leading species after FMT.Mice fed with a controlled diet showed a lower enterotype change rate(23.5%)than those fed with a noncontrolled diet(49.0%),suggesting a possible solution for rescue.Most of the variable taxa have been reported to be implicated in human diseases,with some recognized as the causative species.Our results highlight the challenges of using a mouse model to replicate human gut microbiota-associated phenotypes,provide useful information for researchers using mice in gut microbiota studies,and call for additional validations after FMT.An online database named FMT-DB is publicly available at http://fmt2mice.humangut.info/#/.

Physiological strategies in wild rodents:immune defenses of commensal rats

The importance of issues associated with urban/commensal rats and mice(property damage,management costs,and health risks)press upon research on these animals.While the demography of commensal rodents is mostly studied,the need for understanding factors influencing their natural morbidity/mortality is also stressed.In this respect,more attention is expected to be paid to immunity,the physiological mechanism of defense against host survival threats(pathogens,parasites,diseases).Commensal rats and mice carry numerous pathogens that evoke diverse immune responses.The state of immunity in commensal house mice is studied in great detail,owing to the use of laboratory strains in biomedical research.Because commensal rats are,compared to mice,carriers of more zoonotic agents,rats’immunity is studied mainly in that context.Some of these zoonotic agents cause chronic,asymptomatic infections,which justified studies of immunological mechanisms of pathogen tolerance versus clearance regulation in rats.Occurrence of some infections in specific tissues/organs pressed upon analysis of local/regional immune responses and/or immunopathology.A survey of immunological activity/responses in commensal rats is given in this review,with mention of existing data in commensal mice.It should throw some light on the factors relevant to their morbidity and lifespan,supplementing the knowledge of commensal rodent ecology.

多花黄精水提物成分分析及抗肿瘤活性研究

目的分析多花黄精水提物成分,并对其体内外抗肿瘤活性进行评价,为进一步开发利用多花黄精提供理论基础。方法(1)通过水提法制备多花黄精水提物,利用UPLC-Q-TOF/MS、苯酚硫酸法等方法分析多花黄精水提物化学成分,并通过CCK-8法检测多花黄精水提物对多种肿瘤细胞增殖抑制活性,采用流式细胞术检测细胞周期和凋亡情况,用Western Blot法检测凋亡相关蛋白Bcl-2和Bax的表达情况,利用多花黄精水提物含药血清检测入血成分对细胞增殖抑制活性。(2)构建荷瘤小鼠模型,随机分为模型组(予以生理盐水)、阳性药环磷酰胺组(50 mg·kg^(-1))以及多花黄精水提物低、中、高剂量组(55.9、111.8、223.6 mg·kg^(-1)),灌胃治疗7 d。治疗期间,观察小鼠体质量及肿瘤体积变化情况。治疗结束后处死小鼠,采用苏木素-伊红(HE)染色观察心、肝、脾、肺、肾以及肿瘤组织病理学变化;免疫组化(IHC)检测肿瘤组织Bcl-2及Bax蛋白表达情况。结果多花黄精水提物多糖含量达到(10.07±1.3)%,黄酮含量为(0.044±0.004)%,并且通过UPLC-Q-TOF/MS检测出39种成分,包含黄酮类的黄芩素、槲皮素、木犀草素、芦丁,有机酸类的阿魏酸及多酚类的没食子酸等抗肿瘤成分。多花黄精水提物对Hela、A549、4T1、B16、MFC和HepG2细胞均有抑制作用(P<0.001),其中对B16细胞抑制作用最为明显,且多花黄精水提物可诱导B16细胞周期阻滞于G0/G1期(P<0.001)。流式双染和Western Blot结果显示多花黄精水提物明显促进B16细胞凋亡,降低Bcl-2的表达,且促进Bax的表达(P<0.01,P<0.001)。多花黄精水提物入血成分对B16细胞也具有抑制作用(P<0.001)。此外,多花黄精水提物体内活性实验结果显示,与模型组比较,不同剂量的多花黄精水提物能够抑制肿瘤生长,诱导肿瘤细胞坏死,降低Bcl-2表达,提高Bax的表达。结论多花黄精水提物成分丰富,含有多种抗肿瘤活性成分,能抑制肿瘤生长,诱导肿瘤细胞凋亡,显示较强的抗肿瘤作用,值得深入研究。

药源性心脏毒性模型的构建与评价进展

目的了解药源性心脏毒性动物模型的建立与应用,为药源性心脏毒性的防治提供研究基础。方法采用文献研究,以“心脏毒性”和“cardiotoxicity”等为主题词,在中国知网和Web of science core collection数据库选取2015年1月1日至2024年4月4日应用药源性心脏毒性模型的相关文献,按照纳入标准筛选出应用药源性心脏毒性动物模型的实验研究文献,并使用分析软件Citespace 6.3R1(64-bit)Basic结合Excel对纳入文献进行可视化呈现。结果共纳入731篇文献。应用于药源性心脏毒性研究的模式动物多选用大鼠、小鼠、斑马鱼,造模剂以阿霉素、乌头碱、布比卡因为主,毒性机制涉及氧化应激、细胞凋亡等。大多采用一般指标、组织病理指标、心脏功能检测指标等多类别指标变化进行综合评价。其应用也较为集中,评价药源性心脏毒性模型的标准存在较大差异。结论目前药源性心脏毒性模型的研究仍具有一定的发展前景,为系统开展中医药防治药源性心脏毒性提供依据。

变应性鼻炎相关动物模型研究进展

目的综述变应性鼻炎(allergic rhinitis,AR)相关动物模型的研究进展,为深入研究AR的发病机制及药物评价提供参考。方法通过对国内外文献的查阅,从AR模型动物的种类、特点、模型种类、建模方法、模型成功的标准和评价指标等方面进行总结。结果变应性鼻炎相关动物模型包括西医病理模型和中医病症结合模型,动物选择多使用豚鼠、小鼠、大鼠、新西兰兔等。结论总结已有AR动物模型的种类、方法和评价指标以及在AR发病机制研究中的应用,可为后续AR的深入研究提供参考。

贝那普利灌胃对糖尿病肾病大鼠肾组织连接蛋白表达的影响

目的探讨贝那普利对于糖尿病肾病大鼠肾脏连接蛋白(Cxs)表达的影响。方法将SD雄性大鼠分为对照组、糖尿病组、干预组,糖尿病组及干预组予以STZ 65 mg/kg一次性左下腹注射建立Ⅰ型糖尿病模型,对照组予以相同剂量的枸橼酸盐缓冲液腹腔注射。造模成功后第2天开始,干预组予贝那普利10 mg/(kg·d)每日定时灌胃,对照组和糖尿病组给予等量0.9%氯化钠溶液灌胃,治疗8周,测量各组体质量,采用酶电解层析法检测空腹血糖,采用双抗体夹心法检测尿微量白蛋白;分别应用肌氨酸氧化酶法、酶偶联速率法检测血肌酐、血尿素。8周后处死大鼠,应用SABC法观察连接蛋白Cx37、Cx40、Cx43在肾脏病理组织的分布,免疫组化法检测连接蛋白Cx37、Cx40、Cx43表达,RT-qRCR法检测Cx37、Cx40、Cx43 mRNA表达。结果与对照组相比,糖尿病组及干预组大鼠体质量较前明显下降,血糖较前明显升高(P均<0.05);干预组血尿素、血肌酐、尿微量白蛋白较糖尿病组均明显下降(P均<0.05)。糖尿病组Cx37、Cx43在出入球小动脉、近端肾小管分布明显减弱,干预组Cx37、Cx43在近端肾小管表达明显升高,糖尿病组可见Cx40在多处入球小动脉、致密斑分布明显减弱,干预组Cx40在致密斑分布增强。与糖尿病组比较,干预组Cx37、Cx40表达升高,差异有统计学意义(P均<0.05);干预组Cx43表达高于糖尿病组,差异无统计学意义(P>0.05)。Cx37 C_(T)值在糖尿病组明显升高,且对照组Cx37 C_(T)值高于干预组(P均<0.05)。三组Cx40 C_(T)值差异无统计学意义,干预组Cx40 C_(T)值较糖尿病组明显减小(P<0.05)。与对照组比较,糖尿病组Cx43 C_(T)值明显下降,干预组Cx43 C_(T)值明显上升,三组Cx43 C_(T)值差异均有统计学意义(P均<0.05)。结论贝那普利可上调糖尿病肾病大鼠肾脏连接蛋白表达,改善糖尿病肾病大鼠肾脏病理损伤,保护肾脏,延缓疾病进展。

珠子参对慢性咽炎模型大鼠的干预作用及其急性毒性研究

目的探究珠子参对大鼠慢性咽炎的干预作用及急性毒性。方法单次最大体积灌胃昆明种小鼠74.4 g·kg^(-1)珠子参,通过检测小鼠存活状态、脏器系数、主要脏器组织形态、血常规和生化指标来评价珠子参毒性。SD大鼠随机分为对照组、模型组、阳性对照(醋酸泼尼松片)组(6.25 mg·kg^(-1)),珠子参低、中、高剂量组(0.58,1.16,2.32 g·kg^(-1)),连续灌胃30 d,每天1次;除对照组外,其余各组采用乙型溶血性链球菌诱导大鼠感染慢性咽炎;处死大鼠后,测定血清炎症因子白细胞介素6(Interlukin-6,IL-6)、环氧合酶2(Cyclooxygenase-2,COX-2)、白细胞介素1β(Interlukin-1β,IL-1β)、细胞间黏附分子1(Intercellular celladhesion molecule-1,ICAM-1)、C反应蛋白(C-reactive protein,CRP)、肿瘤坏死因子α(Tumor necrosis factor,TNF-α)、单核细胞趋化蛋白1(Monocyte chemoattractant protein-1,MCP-1)、前列腺素E2(Prostaglandin E2,PGE2)水平,HE染色观察咽部组织形态改变。结果毒理研究发现,给予珠子参后,除小鼠血浆丙氨酸转氨酶(Alanine transaminase,ALT)水平(P<0.05)及脾脏系数(P<0.01)明显升高并伴随组织病理改变外,其余脏器未见明显病理变化,且血常规和血浆生化指标无明显变化;药效研究发现,珠子参明显降低慢性咽炎模型大鼠血清炎症因子水平(P<0.05,P<0.01,P<0.001),改善其咽部组织病理变化。结论珠子参可通过抑制炎症反应缓解乙型溶血性链球菌诱导的慢性咽炎,但对脾脏可能具有潜在毒性。