雷公藤红素对蛋氨酸-胆碱缺乏饮食致小鼠NASH的干预作用及机制研究
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篇名: 雷公藤红素对蛋氨酸-胆碱缺乏饮食致小鼠NASH的干预作用及机制研究
TITLE: Intervention Effect and Mechanism of Celastrol on NASH Induced by Methionine-choline Deficiency Diet in Mice
摘要: 目的:研究雷公藤红素对蛋氨酸-胆碱缺乏(MCD)饮食致小鼠非酒精性脂肪性肝炎(NASH)的干预作用及可能机制。方法:将雄性C57BL/6J小鼠随机分为正常对照组、模型组和雷公藤红素低、高剂量组[0.5、1mg/(kg·d)],每组7只。正常对照组小鼠给予蛋氨酸-胆碱充足饮食,模型组和给药组小鼠给予MCD饮食以复制NASH模型;与此同时,正常对照组和模型组小鼠灌胃聚氧乙烯蓖麻油,各药物组小鼠灌胃相应药物,灌胃体积均为0.1mL/g,每日1次,连续4周。观察各组小鼠肝脏形态,并采用苏木精-伊红染色和油红O染色法观察其肝组织的病理学变化;采用酶法检测血清肝酶[天冬氨酸转氨酶、丙氨酸转氨酶]、血清和肝组织中脂质指标[总胆固醇(TC)、三酰甘油(TG)]水平;采用Westernblotting法检测小鼠肝组织中核因子κBp65(NF-κBp65)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)的蛋白表达水平。结果:与正常对照组比较,模型组小鼠肝脏体积缩小且颜色泛黄,表面粗糙,肝组织中可见炎性细胞浸润以及脂肪空泡、脂滴聚集;其血清TC、TG水平均显著降低,血清肝酶水平以及肝组织中TG水平和NF-κBp65、TNF-α、IL-6蛋白表达水平均显著升高(P<0.01)。与模型组比较,各药物组小鼠肝脏表面红润光滑,无褐色斑点,肝组织中炎性细胞、脂肪空泡有所减少,脂滴覆盖面积有所缩小;其血清TC、TG水平均显著升高,血清肝酶水平以及肝组织中TG水平和NF-κB、TNF-α、IL-6(雷公藤红素低剂量组除外)的蛋白表达水平均显著降低(P<0.05或P<0.01)。结论:雷公藤红素能改善MCD饮食致NASH模型小鼠的肝损伤,其作用与减少肝组织中TG堆积、抑制炎症相关因子表达有关。
ABSTRACT: OBJECTIVE:To study the intervention eff ects and pot ential m echanism of celastrol on non-alcoholic steatohepatitis (NASH)induced by methionine-choline deficiency (MCD)diet. METHODS :Male C 57BL/6J mice were randomly divided into normal control group ,model group ,celastrol low-dose and high-dose groups [ 0.5,1 mg/(kg·d)],with 7 mice in each group. The normal control group was given a methionine-choline sufficient diet ,while the model group and administration groups were fed an MCD diet to induce NASH model. At the same time ,normal control group and model group were given polyoxyethylene castor oil intragastrically;administration groups were given relevant drugs intragastrically ;the volume of gavage was 0.1 mL/g,once a day , for consecutive 4 weeks. The liver morphology was observed ,and the pathological changes of liver tissue were observed by HE staining and oil red O staining. The levels of serum liver enzymes (AST,ALT),and the levels of lipid indexes (TC,TG)in serum and liver tissue were detected by enzyme method. The protein expression of NF-κB p65,TNF-α and IL-6 in liver tissue were determined by Western blotting assay. RESULTS :Compared with normal control group ,the volume of the liver was reduced and the color was yellow ,and the surface was rough in model group ;inflammatory cell infiltration ,fat vacuoles and lipid droplets aggregation were found in the liver tissue ;the serum levels of TC and TG were significantly decreased ,the levels of serum liver enzymes and protein expression of NF-κB p65,TNF-α and IL-6 in liver tissue were significantly increased (P<0.01). Compared with model group ,the liver surface of each administration group was ruddy and smooth without brown spots ,the inflammatory cells and fat vacuoles in liver tissue were reduced ,and the coverage area of lipid droplets was reduced ;the levels of serum TC and TG were significantly increased ,the levels of serum liver enzymes ,the levels of TG and protein expression of NF-κB,TNF-α and IL-6(except for celastrol low-dose group )in liver tissue were significantly decreased (P<0.05 or P<0.01). CONCLUSIONS : Celastrol can improve the liver injury of NASH model mice induced by MCD diet ,which is related to the reduction of TG accumulation in liver tissue and inhibition of the expression of inflammatory related factors.
期刊: 2021年第32卷第01期
作者: 饶辉,盛磊,吴丹妮,吴勇,胡俊杰,郑国华,王桂红
AUTHORS: RAO Hui,SHENG Lei,WU Danni,WU Yong,HU Junjie,ZHENG Guohua ,WANG Guihong
关键字: 雷公藤红素;蛋氨酸-胆碱缺乏饮食;非酒精性脂肪性肝炎;机制;小鼠
KEYWORDS: Celastrol; Methionine-choline deficiency
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