【摘要】 目的探讨阿托伐他汀钙对百草枯致肺纤维化大鼠MMP-9及TIMP-1表达的影响。方法 45只SPF级雄性Wister大鼠,随机分为3组,正常对照组、百草枯组(模型组)、阿托伐他汀干预组(治疗组),每组15只。百草枯组和阿托伐他汀干预组均以百草枯50 mg/kg灌胃染毒建立大鼠肺纤维化模型。阿托伐他汀干预组给予阿伐他汀钙的生理盐水悬混液20 mg/kg灌胃给药,给药体积为200 u L。分别于中毒后第7、14、28天随机处理各组中5只大鼠进行实验观察。分离右肺组织(1 cm×1 cm×0.3 cm),96 h后行石蜡包埋切片。RT-PCR检测肺组织MMP-9、TIMP-1mRNA的表达,Western-blot检测肺组织MMP-9、TIMP-1蛋白的表达。结果 MMP-9 mRNA表达结果阿托伐他汀钙治疗组高于对照组,但低于模型组。TIMP-1 mRNA表达结果正常对照组稍低,其余两组差别不大。肺组织MMP-9、TIMP-1蛋白的表达,百草枯中毒大鼠肺组织内MMP-9及TIMP-1的表达明显高于对照组及治疗组,治疗组两个细胞因子表达高于对照组,但显著低于模型组。结论阿托伐他汀可以抑制百草枯中毒大鼠肺内MMP-9/TIMP-1的表达,拮抗百草枯所致的肺纤维化。更多还原

【Abstract】 Objective To investigate the effect of atorvastatin calcium on the expression of matrix metalloproteinases( MMPs) and their inhibitors( TIMPs) in rats with pulmonary fibrosis induced by paraquat. Methods 45 SFB grade male Wister rats were randomly divided into 3 groups,normal control group,paraquat- injuried group( model group),atorvastatin- treated group( treatment group). Each group had 15 rats. Paraquat- injuried group and atorvastatin- treated group were both treated with paraquat( 50 mg / kg) by gastric lavage to establish the model of pulmonary fibrosis in rats. Atorvastatin-treated group was administered with atorvastatin calcium saline suspension( 20 mg / kg). The administration volume was 200μL. Five random rats in each group were sacrificed for analysis at 7d,14 d and 28 d after poisoning,respectively. The right lung tissues( 1 cm × 1 cm × 0. 3 cm) were harvested and embedded by paraffin after 96 h. The paraffin sections were analyzed via RT- PCR and wester- blot to detect the expression of MMP- 9 and TIMP- 1mRNA proteins and their mRNAs in lung tissues respectively. Results The expression of MMP- 9 mRNA in atorvastatin- treated group was higher than that in the control group,but lower than that in the model group. TIMP- 1 mRNA expressions in model group and treatment group were not significantly different and slightly higher than that in the normal control group. The expression of MMP- 9 and TIMP- 1 proteins in treatment group was slightly higher than that in the control group and significantly lower than that in paraquat- injuried model group. Conclusion Atorvastatin can inhibit the expression of- 9 / TIMP- 1 MMP in the lung of paraquat poisoning rats,and prevent the lung fibrosis induced by paraquat.更多还原