大麻二酚对大鼠非酒精性脂肪肝的治疗作用及机制

发布时间：2018-08-16 12:22

【摘要】：目的观察大麻二酚(CBD)对蛋氨酸/胆碱缺乏饲料(MCD)诱导的大鼠非酒精性脂肪肝(NASH)的治疗作用并探讨其分子机制。方法 63只成年雄性SD大鼠随机分为对照组(给予正常饲料)、MCD组(给予MCD喂养)和MCD+CBD组[给予MCD,同时给予2mg/(kg·d)CBD腹腔注射]。10周后,组织染色法观察大鼠肝脏病理变化及纤维化情况,采用全自动生物化学分析仪检测血清丙氨酸转氨酶(AST)、天冬氨酸转氨酶(ALT)水平,生化试剂盒检测肝脏中胆固醇和甘油三酯水平,Western blotting法观察肝细胞自噬活性的变化。结果 MCD喂养的大鼠给予CBD后,肝脏的病理改变明显减轻(4.7±1.1 vs.2.2±0.5,P0.05),血清ALT(214.5±54.1U/L vs.92.1±36.0U/L,P0.05)和AST(175.9±55.2U/L vs.70.8±24.9U/L,P0.05)水平明显下降,肝脏/体重比(%)降低(4.2±0.6 vs.3.1±0.6,P0.05),肝脏中胆固醇(182.4±42.7mmol/mg protein vs.101.0±33.8mmol/mg protein,P0.05)和甘油三酯(71.4±12.5mmol/mg protein vs.38.7±11.1mmol/mg protein,P0.05)含量减少;肝脏的纤维化程度降低(1.4%±0.4%vs.0.8%±0.3%,P0.05),Ⅰ型α1胶原(Col1A1)m RNA水平明显下降(2.9±0.4 vs.1.6±0.3,P0.05)。CBD治疗后,MCD大鼠肝脏中Ⅱ型微管相关蛋白1轻链3(LC3-Ⅱ)/LC3-Ⅰ比值增加(37.1±10.8 vs.71.2±17.1,P0.05),可溶性死骨片1(p62)蛋白水平降低(202.4±40.9 vs.125.8±32.7,P0.05)。结论CBD减轻了MCD诱导的大鼠NASH症状,CBD对肝细胞自噬流的促进可能是其肝脏保护作用的机制之一。
[Abstract]:Objective to investigate the therapeutic effect of cannabinol (CBD) on (NASH) induced by methionine / choline deficiency diet (MCD) in rats with non-alcoholic fatty liver and to explore its molecular mechanism. Methods Sixty-three adult male Sprague-Dawley rats were randomly divided into two groups: control group (normal diet) and MCD CBD group (treated with MCD and 2mg/ (kg d) CBD intraperitoneal injection) for 10 weeks. Histopathological changes and fibrosis of rat liver were observed by tissue staining. Serum alanine aminotransferase (AST),) aspartate transaminase (ALT) levels were detected by automatic biochemistry analyzer. The levels of cholesterol and triglyceride in liver were detected by biochemical kit. The changes of autophagy activity of hepatocytes were observed by Western blotting. 缁撴灉 MCD鍠傚吇鐨勫ぇ榧犵粰浜圕BD鍚，

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