机构地区:[1]生物资源保护与利用湖北省重点实验室,湖北恩施445000 [2]湖北民族学院医学院,湖北恩施445000
出 处:《中国药理学与毒理学杂志》2015年第4期578-584,共7页Chinese Journal of Pharmacology and Toxicology
基 金:生物资源保护与利用湖北省重点实验室项目(PKLHB1308);湖北省教育厅科学技术重点项目(D20131904)~~
摘 要:目的探讨延龄草(TTM)正丁醇萃取物对非酒精性脂肪肝的治疗作用,并探讨其可能的作用机制。方法 50只Wistar大鼠分成5组,正常对照组、高脂模型组、模型+TTM正丁醇萃取物50,100和200mg·kg-1组。高脂模型组喂高脂饲料;给药组喂高脂饲料4周后ig给予TTM正丁醇萃取物,每天1次,共6周。取大鼠肝组织HE常规染色及苏丹Ⅲ染色观察肝组织病理变化和肝脂肪变性程度。用全自动生化分析仪测定血清谷丙转氨酶(GPT)和谷草转氨酶(GOT)活性、总胆固醇(TC)和甘油三酯(TG)水平及肝匀浆中谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)含量的变化。免疫组织化学法和RT-PCR测定肝组织葡萄糖调节蛋白78(GRP78)蛋白和m RNA表达。结果模型组肝脂肪变性程度、血清GPT和GOT活性、TC和TG水平及肝组织MDA含量均高于正常对照组(P<0.05),肝组织GSH-Px含量明显低于正常对照组(P<0.05)。TTM正丁醇萃取物50,100和200 mg·kg-1组肝组织脂肪变性程度、血清GPT和GOT活性和MDA含量均低于模型组(P<0.05),各剂量组间无明显差异。与正常对照组相比,模型组肝组织GRP78 m RNA和蛋白表达增加(P<0.01)。与模型组相比,TTM正丁醇萃取物50,100和200 mg·kg-1组肝组织GRP78m RNA和蛋白表达明显降低(P<0.05),不同剂量组间无明显差异。结论 TTM正丁醇萃取物能有效减轻非酒精性脂肪肝大鼠肝损伤和脂肪变性程度,该作用可能与其提高非酒精性脂肪肝的抗氧化酶活性及降低肝组织内质网应激作用有关。OBJECTIVE To investigate the efficacy of n-butylethyl extract from Trillium tschonoskii Maxim. (TTM) for non- alcoholic fatty liver disease and its possible mechanism. METHODS Fifty Wistar rats were randomly divided into 5 groups, normal control group, model group fed with high-fat diet, experimental groups fed with high-fat forage and 4 weeks later ig coadministered with n-butylethyl extract from TTM 50, 100 and 200 mg· kg^-1, respectively, once a day, for 6 weeks. The pathological changes and pimelosis level of liver tissue were investigated by HE staining and Sudan III staining, respectively. The activity of serum gl utamic-pyruvic transaminase ( GPT) and glutamic-oxal (o) acetic transaminase (GOT), the level of blood total cholesterol (TC)and triglycerides (TG), the content of glutathione peroxidase (GSH- Px) and malonyldialdehyde (MDA) in liver tissues were analyzed respectively by auto-biochemical in- strument. The mRNA and protein expression of hepatic glucose regulated protein 78 (GRP78) in liver tissue was detected by immunohistochemical assay and RT-PCR. RESULTS The degree of fatty degeneration, activity of serum GPT and GOT, level of blood TC and TG, and content of MDA in liver tissue in model group were obviously higher than in normal control group(P〈0.05), while the level of GSH-Px in model group was lower than that of normal control group (P〈0.05). Compared with model group, the fatty degenertion degree, level ofGPT, GOT, TC, TG and MDA became significantly lower and the expression decreased in n-butylethyl extract from TTM 50, 100 and 200 mg· kg^-1 groups (P〈0.05), but there was no significant difference in the degree of change between the groups of different doses. Moreover, the expression of GRP78 mRNA and protein in liver tissue in model group was higher than that in normal control group (P〈0.01 ). CONCLUSION n-Butylethyl extract from TTM can effectively prevent liver cell injury and reduce fatty degeneration of the liver in NAFLD rat
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