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目的:观察膈下逐瘀汤对非酒精性脂肪性肝炎(NASH)大鼠肝脏脂肪酸代谢酶的影响,探讨膈下逐瘀汤防治NASH的作用机制。方法:30只SD雄性大鼠随机分为正常组、模型组、膈下逐瘀汤组,每组10只,正常组予标准饲料喂养,其他两组予高脂饲料喂养,同时膈下逐瘀汤组予14g/(kg.d)的膈下逐瘀汤流浸膏灌胃,正常组和模型组以等容量的蒸馏水灌胃,连续12周。HE染色后光镜下观察肝脏组织病理学改变;生化法测定肝组织匀浆TG、CHOL含量;ELISA法检测血清游离脂肪酸(FAA)和肝组织脂肪酸合酶(FAS)、乙酰CoA羧化酶(ACC)、肉毒碱棕榈酸转移酶-1(CPT-1)、硬脂酰辅酶A去饱和酶-1(SCD-1)含量。结果:模型组大鼠肝组织出现重度脂肪变,肝细胞气球样变,肝小叶出现不同程度的炎细胞浸润和点片状坏死灶;肝脏NAFLD活动度积分(NAS)较正常组明显增高(P<0.01),血清FAA和肝组织TG、CHOL含量较正常组明显增高(P<0.01);肝组织ACC、FAS表达较正常组显著升高(P<0.01),而CPT-1、SCD-1蛋白表达则较正常组明显下降(P<0.01)。应用膈下逐瘀汤干预后,大鼠肝组织NAS较模型组明显下降(P<0.05);血清FAA、肝组织TG、CHOL水平及ACC、FAS表达均较模型组显著下降(P<0.01,P<0.05);而肝组织CPT-1和SCD-1表达则较模型组明显升高(P<0.01,P<0.05)。结论:高脂饮食诱导的NASH大鼠存在着脂肪酸代谢紊乱;膈下逐瘀汤能一定程度纠正肝组织脂肪酸代谢酶的紊乱,减少脂肪酸对肝脏损伤有关,这可能是其防治NASH的作用机制之一。
Objective: To observe the effect of Gexia Zhuyu Decoction on hepatic fatty acid metabolizing enzymes in rats with non-alcoholic steatohepatitis (NASH), and to explore the mechanism of action of Gexia Zhuyu Decoction in preventing and treating NASH. Methods: Thirty SD male rats were randomly divided into normal group, model group and Gexia Zhuyu Decoction group, with 10 rats in each group. The normal group was fed with standard diet and the other two groups were fed with high fat diet. At the same time, The soup group was given 14g / (kg.d) of Gexiazhuyu decoction infusion, normal group and model group with equal volume of distilled water for 12 weeks. Histopathological changes of liver were observed by HE staining; TG and CHOL content in liver homogenate were determined by biochemical method; serum free fatty acid (FAA) and fatty acid synthase (FAS), acetyl CoA carboxylase ACC), carnitine palmitoyl transferase-1 (CPT-1) and stearoyl-CoA desaturase-1 (SCD-1) Results: The model rats showed severe steatosis, hepatocellular ballooning and inflammatory cell infiltration and punctate necrosis in hepatic lobules. The NAFLD activity score (NAS) in the liver of the model group was significantly higher than that of the normal group (P (P <0.01). The levels of serum FAA and liver tissue TG and CHOL in liver tissue were significantly higher than those in normal group (P <0.01). The expression of ACC and FAS in liver tissue were significantly higher than those in normal group (P <0.01) Protein expression was significantly lower than the normal group (P <0.01). After intervention with Gexia Zhuyu Decoction, the level of NAS in rat liver tissue was significantly lower than that in model group (P <0.05); the levels of FAA, TG and CHOL in liver tissue and the expression of ACC and FAS in liver tissue were significantly lower than those in model group (P <0.01, P <0.05). The expressions of CPT-1 and SCD-1 in liver tissue were significantly higher than those in model group (P <0.01, P <0.05). CONCLUSION: Fatty acid metabolism disorder exists in NASH rats induced by high-fat diet. Gexiazhuyutang can correct the disorder of fatty acid metabolism enzyme in liver tissue and reduce the fatty acid’s damage to liver to a certain extent, which may be the mechanism of its prevention and treatment of NASH one.