复合磷酸酯酶肠溶片对酒精性脂肪肝的保护作用考察

Protective Function of Phosphoesterase Complex Enteric-coated Tablets against Alcoholic Fatty Liver Disease

探讨复合磷酸酯酶肠溶片(1)对酒精性脂肪肝大鼠的保护作用。将60只完成肠瘘手术的Wistar大鼠随机分为正常组、对照组、模型组、1(30、60 mg/kg)组和多烯磷脂酰胆碱胶囊(140 mg/kg)组,每组10只。给予Lieber-De Carli酒精液体饲料诱导大鼠酒精性脂肪肝模型,边造模边给药,共给药6周。第6周试验结束后,检测各组大鼠血生化指标、肝脏组织病理学变化、脂肪代谢相关基因的表达及氧化应激及脂质过氧化水平变化;通过Tunel染色和检测凋亡相关蛋白表达考察1对肝细胞凋亡的影响。结果表明,与模型组相比,1组大鼠血脂水平明显下降,肝脏脂质沉积减少,纤维化程度降低,脂肪代谢基因脂肪酸合成酶(FAS)、甘油-3-磷酸酰基转移酶1(GPAT1)及固醇调节元件结合蛋白-1c(SREBP-1c)表达明显下调(P<0.05或0.01),线粒体活力、总超氧化物歧化酶(T-SOD)、谷胱甘肽过氧化物酶(GSH-PX)水平明显升高(P<0.05或0.01),同时1 30 mg/kg组丙二醛(MDA)及活性氧簇(ROS)水平显著降低(P<0.05或0.01)。Tunel染色及Western Blot检测结果显示1 30 mg/kg组肝细胞凋亡程度明显降低。上述结果说明1对酒精性脂肪肝有保护作用,能够降低肝脏脂肪含量,改善肝脏氧化应激水平,有效抑制肝细胞凋亡,显著修复肝细胞损伤。

This paper was aimed to explore the protective effect of the phosphoesterase complex entericcoated tablets （1） on alcoholic fatty liver disease （AFLD）. Sixty Wistar rats after surgery treatment of intestinal fistula were randomly divided into six groups of 10 rats each group： normal group, blank control group, model group, 1 （30,60 mg/kg） groups and the polyene phosphatidylcholine capsules （140 mg/kg） group. The AFLD rat model was established by feeding Lieber-DeCarli liquid diet containing ethanol for 6 weeks with continuous administration for 6 weeks. Alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, total cholesterol （TC）, low density lipoprotein-cholesterol （LDL-C） in serum and malondialdehyde （MDA）, total superoxide dismutase （T-SOD）, glutathione peroxidase （GSH-PX） in liver tissue were measured, respectively. The expressions of fat metabolism-related genes were evaluated by real-time quantitative PCR. Oxidative stress parameters including mitochondrial viability and mitochondrial reactive oxygen species （ROS） accumulation were detected. Hepatocyte apoptosis was determined by Tunel staining and the expressions of apoptosis-related proteins, such as caspase-7, cleaved caspase-3, cleaved caspase-9 and Bcl-2 were assessed by Western Blot. Our results showed that serum AST, TC and LDL-C levels were lowered by 1 of 30 mg/kg, while TC level was lowered by 1 of 60 mg/kg, compared to those of the model group. Hepatic histopathology showed that 1 was effective in reducing hepatic fat deposition. 1 treatment downregulated the expression of fatty acid synthase （FAS）, glycerol-3-phosphate acyltransferase 1（GPAT1） and sterol regulatory element binding protein 1c （SREBP-1c）. In addition, 1 could dramatically alleviate oxidative stress by elevating T-SOD, GSH-PX and mitochondrial viability in hepatocytes, moreover, 1 of 30 mg/kg could also decrease MDA and mitochondrial ROS accumulation. Finally, 1 of 30 mg/kg remarkably suppressed hepatocyte apoptosis. These findings suggested that 1 exerted a protective effect on AFLD through inhibiting oxidative stress and apoptosis in hepatocytes.