四物汤对非酒精性脂肪性肝病小鼠的作用机制研究

Mechanism study of Siwu decoction on non-alcoholic fatty liver in mice

目的研究四物汤对非酒精性脂肪性肝病(NAFLD)小鼠的作用机制。方法将60只C57健康雄性小鼠适应性喂养5 d后,按照随机数字表法分为5组,分别为正常对照组,模型组,四物汤低、中、高剂量组,每组各12只。正常对照组小鼠予正常饲料喂养,其余4组小鼠予高脂饲料喂养,自由进食,连续4周,建立NAFLD模型。造模成功后,正常对照组及模型组小鼠予0.9%氯化钠注射液0.2 m L/100 g灌胃,四物汤低、中、高剂量组小鼠分别予0.05、0.10、0.20 m L/100 g四物汤药液灌胃,均每日2次,连续6周。然后取各组小鼠血清标本,检测血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平;取肝组织,检测游离脂肪酸(FFA)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)及超氧化物歧化酶(SOD)活性,并对肝脏组织形态学进行观察。结果与正常对照组相比,模型组小鼠血清TG、TC、ALT、AST水平均增高(P<0.05),HDL-C水平降低(P<0.05)。与模型组相比,四物汤低、中、高剂量组小鼠血清TG、TC、ALT、AST水平均显著降低(P<0.05),HDL-C水平增高(P<0.05),且与正常对照组比较差异均无统计学意义(P>0.05)。与正常对照组相比,模型组肝组织MDA、FFA活性均升高(P<0.05),GSH-Px、SOD活性均降低(P<0.05);与模型组相比,四物汤低、中、高剂量组肝组织MDA、FFA活性均降低(P<0.05),GSH-Px、SOD活性均增高(P<0.05),且与正常对照组比较差异均无统计学意义(P>0.05)。结论四物汤可通过调节血脂水平,改善脂质代谢紊乱,提高肝脏抗氧化能力,从而起到控制NAFLD进展以及其恶化程度的作用。

Objective To study the mechanism of Siwu decoction on non-alcoholic fatty liver disease（ NAFLD） in mice. Methods 60 healthy C57 male mice after 5 d adaptive feed were divided into normal group,model control group,Siwu decoction low,middle and high dose group according to random number table,12 mice in each group. The normal control group was fed by normal forage,the rest four groups were fed by high fat feed,freely eating for 4 weeks. After successful modeling,the mice in normal and model group received 0. 9% sodium chloride injection（ 0. 2 m L/100 g） by gavage,the Siwu decoction low,middle and high dose group received Siwu decoction at0. 05 m L/100 g,0. 1 m L/100 g and 0. 2 m L/100 g respectively,2 times a day for 6 weeks. The triglyceride（ TG）,total cholesterol（ TC）,high-density lipoprotein cholesterol（ HDL-C）,alanine aminotransferase（ ALT） and aspartate aminotransferase（ AST） in serum sample were measured. The concentrations of free fatty acid（ FFA）,malondialdehyde（ MDA） and glutathione peroxidase（ GSH-Px） and superoxide dismutase（ SOD） in liver tissue were measured,and liver pathologic change was observed. Results As compared with normal control group,the serum TG,TC,ALT and AST in model group were increased（ P〈0. 05）,and the HDL-C was decreased（ P〈0. 05）.As compared with model group,the serum TG,TC,ALT and AST in Siwu decoction low,middle and high dose group were significantly decreased（ P〈0. 05）,and the HDL-C was increased（ P〈0. 05）. There were no statistical differences on TG,TC,ALT,AST and HDL-C among Siwu decoction low,middle,high dose group and normal control group（ P〈0. 05）. As compared with normal control group,the activity of MDA and FFA of liver tissue in model group were increased（ P〈0. 05）,and the activity of GSH-Px and SOD were decreased（ P〉0. 05）. As compared with model group,the activity of MDA and FFA of liver tissue in Siwu decoction low,middle,high dose group were significantly decreased（ P〈0. 05）,and the GSH-Px and SOD were increased（ P〈0. 05）. There were no statistical differences on activity of MDA,FFA,GSH-Px and SOD among Siwu decoction low,middle,high dose group and normal control group（ P〈0. 05）. Conclusion Siwu decoction can adjust the blood lipid,enhance antioxidant capacity of liver,and improve lipid metabolism disorders,which play a role in controlling the progress of NAFLD and its deterioration degree.