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益气逐瘀解毒颗粒调控MMPs/TIMPs平衡抗大鼠肝纤维化作用研究 被引量:6

Study on the Effect of Yiqi Zhuyu Jiedu Granule in Regulating the Balance of MMPs/TIMPs for Anti-liver Fibrosis in Rats
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摘要 目的:探讨益气逐瘀解毒颗粒对四氯化碳(CCl4)诱导的大鼠肝纤维化的治疗作用及机制。方法:将SD雄性大鼠给予CCl4橄榄油混合液进行皮下注射7周,制备肝纤维化大鼠模型,随机分为益气逐瘀解毒颗粒高、中、低剂量组、阳性对照组、模型组、空白组,给予相应治疗,5周后处死大鼠,检测外周血生化指标,逆转录-定量PCR法和蛋白印迹法分别检测大鼠肝组织中基质蛋白酶1 (Matrix metalloproteinase1, MMP-1)、MMP-2、MMP-9、MMP-13及基质蛋白酶抑制因子1 (tissue Inhibitor of metalloproteinases1,TIMP-1)表达水平,肝组织苏木精-伊红(Hematoxylin-Eosin staining, HE染色)、MASSON染色检测肝纤维化程度。结果:治疗后与空白组比较,模型组的ALT、AST无显著性差异(P> 0.05),MMP-1、MMP-2、MMP-9、MMP-13基因表达显著降低(P <0.05),TIMP-1基因表达显著升高(P <0.05),肝纤维化半定量计分(SSS)评分显著升高(P <0.01);与模型组比较,益气逐瘀解毒颗粒各剂量组ALT、AST无显著性差异(P> 0.05),益气逐瘀解毒颗粒高剂量组MMP-1、MMP-2、MMP-9、MMP-13基因表达明显升高(P <0.05),中剂量组MMP-9、MMP-13基因表达明显增高(P <0.05),低剂量组MMP-13基因表达明显增高(P <0.05),高、中剂量组TIMP-1基因表达明显降低(P <0.05),益气逐瘀解毒颗粒各剂量组MMP-2、MMP-9蛋白表达量无显著性差异(P> 0.05),高、中剂量组MMP-13蛋白表达量显著升高(P <0.05),各剂量组TIMP-1蛋白表达量均显著下降(P <0.05),以低剂量组下降尤为显著,优于高、中剂量组(P <0.05),各药物干预组SSS评分显著降低(P <0.01);与阳性对照组比较,益气逐瘀解毒颗粒各剂量组ALT、AST无显著性差异(P> 0.05),益气逐瘀解毒颗粒高剂量组MMP-2基因表达明显升高(P <0.05),高、中剂量组TIMP-1基因表达明显降低(P <0.05),益气逐瘀解毒颗粒高、中剂量组MMP-13蛋白表达显著升高(P <0.05),益气逐瘀解毒颗粒各剂量组TIMP-1蛋白表达显著降� Objective:To observe the clinical effect of Yiqi Zhuyu Jiedu granule for rats with liver fibrosis induced by carbon tetrachloride(CCl4),and its functional mechanism.Methods:The model of SD male rats with liver fibrosis was established by subcutaneous injection of the mixture of CCl4 and olive oil.The rats were divided into the groups of Yiqi Zhuyu Jiedu granule in high,middle and low doses,the positive control group,the model group and the blank group randomly,which received treatment accordingly.After 5 weeks,the rats were sacrificed.Detected biochemical indexes in the peripheral blood,measured the expression levels of matrix metalloproteinase(MMP)-1,MMP-2,MMP-9,MMP-13 and tissue inhibitor of metalloproteinases 1(TIMP-1)in the liver tissue of rats respectively via reverse transcription PCR and Western blot,and detected the degree of liver fibrosis in the liver tissue via hematoxylin-eosin staining(HE)and MASSON staining.Results:After treatment,comparing with the blank group,there was nosignificant difference being found in ALT and AST in the model group(P>0.05),the gene expression levels of MMP-1,MMP-2,MMP-9 and MMP-13 were significantly decreased(P<0.05),the gene expression level of TIMP-1 was significantly increased(P<0.05),and the scores of Semiquantative scorning system(SSS)for liver fibrosis were significantly increased(P<0.01).Comparing with the model group,there was no significant difference being found in ALT and AST in the groups of Yiqi Zhuyu Jiedu granule in each dose(P>0.05),the gene expression levels of MMP-1,MMP-2,MMP-9 and MMP-13 in the high-dose Yiqi Zhuyu Jiedu granule group were significantly increased(P<0.05),the gene expression levels of MMP-9 and MMP-13 in the middle-dose Yiqi Zhuyu Jiedu granule group were significantly increased(P<0.05),the gene expression level of MMP-13 in the low-dose Yiqi Zhuyu Jiedu granule group was significantly increased(P<0.05),and the gene expression level of TIMP-1 in the groups of Yiqi Zhuyu Jiedu granule in high and middle doses was significantly decreased(P<0
作者 李晖 杨琪 韩朋丽 林俊芝 陈婧 赵梓亦 陈昌金 LI Hui;YANG Qi;HAN Pengli;LIN Junzhi;CHEN Jing;ZHAO Ziyi;CHEN Changjin
出处 《新中医》 CAS 2019年第5期17-22,共6页 New Chinese Medicine
基金 四川省科技厅项目(2018SZ0401 2017FZ0052 2016FZ0093) 四川省中医药管理局项目(2016C036) 成都中医药大学附属医院项目(2016-D-YY-06)
关键词 益气逐瘀解毒颗粒 肝纤维化 MMPs/TIMPs平衡 动物实验 大鼠 Yiqi Zhuyu Jiedu granule Liver fibrosis Balance of MMPs/TIMPs Animal experiment Rats
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