论文部分内容阅读
目的:考察苦参碱联合甘草甜素在四氯化碳(CCl_4)慢性肝损伤中的保护作用,并从能量代谢及CYP酶的角度探讨其保护机制。方法:建立CCl_4慢性肝损伤模型,通过考察血清ALT、AST观察两药及其联合用药在慢性肝损伤模型中的保护作用;检测血清谷氨酸脱氢酶(GLDH)及肝组织中肝脏腺嘌呤核苷三磷酸(ATP)、二磷酸腺苷(ADP)、腺嘌呤核糖核苷酸(AMP)含量,评价药物对肝脏能量代谢及线粒体功能的调节作用;实时定量PCR及Western Blot法检测肝脏CYP1A2、CYP2E1 mRNA及蛋白水平,评价两药及其联合用药对肝脏CYP酶的调控作用。结果:苦参碱(72.8 mg·kg~(-1))、甘草甜素(43.4 mg·kg~(-1))在CCl_4慢性肝损伤模型中均可降低大鼠血清ALT、AST(P<0.05),两药联合(36.4 mg·kg~(-1)苦参碱+21.7 mg·kg~(-1)甘草甜素)使用保护作用更加显著(P<0.05);其中苦参碱(72.8 mg·kg~(-1))、甘草甜素(43.4 mg·kg~(-1))均可降低血清GLDH,并恢复肝脏ATP含量(P<0.05);苦参碱(72.8 mg·kg~(-1))对CYP1A2、CYP2E1 mRNA表达水平无抑制作用,甘草甜素(43.4mg·kg~(-1))对CYP1A2、CYP2E1 mRNA及蛋白表达水平均有抑制作用(P<0.05)。结论:苦参碱联合甘草甜素在慢性肝损伤模型中具有明显的线粒功能调节和肝保护作用。
Objective: To investigate the protective effect of matrine combined with glycyrrhizin on chronic liver injury induced by carbon tetrachloride (CCl 4), and to explore its protective mechanism from the aspects of energy metabolism and CYP enzyme. Methods: The model of chronic liver injury induced by CCl 4 was established. The protective effects of two drugs and their combination on chronic liver injury model were observed by examining serum ALT and AST. Serum glutamate dehydrogenase (GLDH) and hepatic adenine (ATP), adenosine diphosphate (ADP) and adenine ribonucleotide (AMP) were measured to evaluate the regulatory effect of drugs on hepatic energy metabolism and mitochondrial function. Real-time quantitative PCR and Western Blot were used to detect the expression of CYP1A2 , CYP2E1 mRNA and protein levels, evaluation of the two drugs and their combination on liver CYP enzyme regulation. Results: Both matrine (72.8 mg · kg -1) and glycyrrhizin (43.4 mg · kg -1) decreased serum ALT and AST levels in CCl 4 - induced chronic liver injury model (P < (P <0.05). The protective effect of the two drugs combined with 36.4 mg · kg -1 matrine and 21.7 mg · kg -1 glycyrrhizin was more significant (P <0.05) mg · kg ~ (-1)) and glycyrrhizin (43.4 mg · kg ~ (-1)) both reduced serum GLDH and restored liver ATP content (P <0.05). Matrine (72.8 mg · kg ~ (-1)) had no effect on the expression of CYP1A2 and CYP2E1 mRNA. Glycyrrhizin (43.4 mg · kg -1) inhibited the expression of CYP1A2 and CYP2E1 mRNA and protein (P <0.05). Conclusion: Matrine combined with glycyrrhizin has obvious regulation of mitochondrial function and liver protection in chronic liver injury model.