【摘要】：目的觀察大麻二酚(CBD)對蛋氨酸/膽堿缺乏飼料(MCD)誘導的大鼠非酒精性脂肪肝(NASH)的治療作用并探討其分子機制。方法 63只成年雄性SD大鼠隨機分為對照組(給予正常飼料)、MCD組(給予MCD喂養(yǎng))和MCD+CBD組[給予MCD,同時給予2mg/(kg·d)CBD腹腔注射]。10周后,組織染色法觀察大鼠肝臟病理變化及纖維化情況,采用全自動生物化學分析儀檢測血清丙氨酸轉氨酶(AST)、天冬氨酸轉氨酶(ALT)水平,生化試劑盒檢測肝臟中膽固醇和甘油三酯水平,Western blotting法觀察肝細胞自噬活性的變化。結果 MCD喂養(yǎng)的大鼠給予CBD后,肝臟的病理改變明顯減輕(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)水平明顯下降,肝臟/體重比(%)降低(4.2±0.6 vs.3.1±0.6,P0.05),肝臟中膽固醇(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)含量減少;肝臟的纖維化程度降低(1.4%±0.4%vs.0.8%±0.3%,P0.05),Ⅰ型α1膠原(Col1A1)m RNA水平明顯下降(2.9±0.4 vs.1.6±0.3,P0.05)。CBD治療后,MCD大鼠肝臟中Ⅱ型微管相關蛋白1輕鏈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)。結論CBD減輕了MCD誘導的大鼠NASH癥狀,CBD對肝細胞自噬流的促進可能是其肝臟保護作用的機制之一。
[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. 緇撴灉 MCD鍠傚吇鐨勫ぇ榧犵粰浜圕BD鍚，

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