异甘草酸镁对肝纤维化大鼠氧化应激反应的影响研究

Study on effect of magnesium isoglycyrrhizinate in reducing oxidative stress of rat with hepatic fibrosis

目的观察异甘草酸镁(Mg IG)对肝纤维化大鼠氧化应激反应指标的影响,探讨异甘草酸镁治疗肝纤维化的机制。方法将24只雄性Wistar大鼠随机分为正常组、模型组和异甘草酸镁组,每组8只。正常组大鼠给予正常饲养,其余2组大鼠均采用四氯化碳(CCl4)建立大鼠肝纤维化模型。建模成功后,模型组与异甘草酸镁组继续给予CCl4皮下注射,每2周注射1次,共8周;异甘草酸镁组同时给予异甘草酸镁30 mg/kg腹腔注射,每日1次,共8周。末次注射24 h后断头取血检测肝功能指标和肝纤维化指标水平,采用实时定量PCR和免疫印迹技术检测肝组织中胶原(Collagen)Ⅰ、CollagenⅢ、基质金属蛋白酶13(MMP-13)和组织金属蛋白酶抑制因子1(TIMP-1)mRNA和蛋白表达情况,采用化学发光法检测肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)含量。结果异甘草酸镁组肝功能指标及肝纤维化指标均较模型组明显改善(P均<0.05),CollagenⅠ、CollagenⅢ和TIMP-1 mRNA和蛋白表达水平及MDA含量均明显低于模型组(P均<0.05),MMP-13 mRNA和蛋白表达水平及SOD、GSH含量均明显高于模型组(P均<0.05)。结论异甘草酸镁可通过降低氧化应激水平起到抗肝纤维化的作用。

Objective It is to observe the influence of magnesium isoglycyrrhizinate （MgIG） on oxidative stress in rats with hepatic fibrosis, and explore its therapeutic mechanism. Methods A total of 24 male Wistar rats were divided into normal group, model group and MgIG group, 8 cases in each groups. The animals in normal group were fed normally, and the other rats were made into animal models of hepatic fibrosis by Carbon tetraehloride （ CCl4 ） in the other two groups. After the success of the model of hepatic fibrosis, the animals were continued to receive subcutaneous injection of CCI4 in model group, 1 times every 2 weeks, a total of 8 weeks; on the basis of the model group, the animals were treated with MgIG of 30 mg/kg by injec- tion intraperitoneally, once a day, a total of 8 weeks. The changes of liver function and liver fibrosis indexes were detected by hematology test; The changes of collagen I, collagen III, matrix metalloproteinase 13 （MMP-13） and tissue inhibitor of metal- loproteinase 1 （TIMP-1） were detected by real-time quantitative PCR and immunoblotting; The contents of malondialdehyde （MDA） , superoxide dismutase （SOD） and glutathione （GSH） in liver tissues were detected by chemiluminescence method. Results Compared with model group, the liver function index and liver fibrosis index in MgIG group were significantly im- proved （ all P 〈 0.05 ） ; the expression of collagen I, collagen III and TIMP-1 was significantly decreased （ all P 〈 0.05 ） , the expression of MMP-13 was significantly increased （ P 〈 0.05 ） , MDA content was significantly decreased （ P 〈 0.05 ） , the lev- els of GSH and SOD were increased significantly （ all P 〈 0.05）. Conclusion MglG can inhibit the hepatic fibrosis by reduc- ing the level of oxidative stress.