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L-色氨酸对四氯化碳诱导的小鼠肝纤维化进程的改善作用

L-tryptohan ameliorate the progression of hepatic fibrosis induced by carbon tetrachloride in mice

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【作者】 杨海郑苑竹李晴凌文华

【Author】 YANG Hai;ZHENG Yuan-zhu;LI Qing;LING Wen-hua;Public Health School,Sun Yat-sen University;

【机构】 中山大学公共卫生学院

【摘要】 目的观察L-色氨酸对四氯化碳诱导的小鼠肝纤维化的作用。方法雄性C57/BL6小鼠15只随机分成正常对照组、肝纤维化模型组和L-色氨酸干预组,8周后处死小鼠,留取肝脏和血清。天狼猩红染色(Sirius Red)以及羟脯氨酸测定观察肝纤维化的程度,同时测定血清或者肝脏中谷草转氨酶(AST)、谷丙转氨酶(ALT)、丙二醛(MDA)、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)的含量。实时定量PCR法(RT-q PCR)测定肝脏组织中基质金属蛋白酶(MMPS)和基质金属蛋白酶抑制剂(TIMPs)基因的表达。结果实验期间各组小鼠平均体重和摄食量差异均无统计学意义。与肝纤维化模型组对比,L-色氨酸干预可以减少天狼猩红染色面积,降低羟脯氨酸含量;同时L-色氨酸可以上调MMP2、MMP13基因以及下调TIMP1基因的表达(P<0.05),但是对TIMP2基因的表达无影响;可以显著降低血清ALT、增加肝脏组织中GSH的含量,但是对血清AST和肝组织中MDA、SOD的影响差异无统计学意义。结论 L-色氨酸可以提高肝脏抗氧化能力、减少细胞外基质(ECM)沉积来发挥改善肝纤维化的作用。

【Abstract】 Objective To observe the effect of L-tryptohan on the mice hepatic fibrosis induced by carbon tetrachloride.Methods Fifteen male C57/BL6 mice were randomly divided into normal control group,hepatic fibrosis group and Ltryptohan supplementation group.After eight weeks,all mice were sacrificed and the liver and serum samples were stored.Grades of hepatic fibrosis were evaluated according to the sirius red staining and the contents of hydroxyproline. The contents of aspartate aminotransferase(AST),alanine transaminase(ALT),malondialdehyde(MDA),superoxide dismutase(SOD) and reduced glutathione hormone(GSH) were determined.The expression of matrix metalloproteinases(MMPs) and the tissue inhibitor of matrix metalloproteinases(TIMPs) gene were detected by real-time quantitative PCR. Results There was no significant difference in body weight and food intake during the experiment.L-tryptohan supplementation could decrease the sirius red positive area and reduce the contents of hydroxyproline as compared with hepatic fibrosis group.Meanwhile,L-tryptohan could up regulate the expressionof MMP2 and MMP13 genes and down regulate the expressionof TIMP1 gene,but it had no effect on the TIMP2 gene expression.Moreover,L-tryptohan could decrease the serum ALT and increase the contents of liver GSH in mice,but it had no significant effect on the levels of serum AST and the contents of MDA and SOD in the liver. Conclusion L-tryptohan could prevent hepatic fibrosis progression through enhance the antioxidant capacity and decrease the accumulation of extracellular matrix(ECM).

【基金】 国家重点基础研究发展计划(973)分题项目(2012CB517506)
  • 【文献出处】 热带医学杂志 ,Journal of Tropical Medicine , 编辑部邮箱 ,2016年03期
  • 【分类号】R575.2
  • 【被引频次】7
  • 【下载频次】201
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