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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。
Objective To investigate the effect of atorvastatin calcium on the expression of MMP-9 and TIMP-1 in paraquat-induced pulmonary fibrosis in rats. Methods Forty-five SPF male Wister rats were randomly divided into 3 groups: normal control group, paraquat group (model group) and atorvastatin intervention group (treatment group), 15 in each group. Paraquat group and atorvastatin intervention group were treated with paraquat 50 mg / kg gavage to establish rat pulmonary fibrosis model. Atorvastatin intervention group given atorvastatin calcium saline suspension 20 mg / kg intragastric administration, the administration volume of 200 u L. Five rats in each group were randomly treated on the 7th, 14th, 28th day after poisoning. Right lung tissue (1 cm × 1 cm × 0.3 cm) was isolated and paraffin-embedded sections were taken after 96 h. The expression of MMP-9 and TIMP-1 mRNA in lung tissue was detected by RT-PCR. The expression of MMP-9 and TIMP-1 in lung tissue was detected by Western-blot. Results The expression of MMP-9 mRNA in atorvastatin treated group was higher than that in control group, but lower than that in model group. The expression of TIMP-1 mRNA in normal control group was slightly lower than other groups. The other two groups showed little difference. The expression of MMP-9 and TIMP-1 in lung tissue and the expression of MMP-9 and TIMP-1 in lung tissues of paraquat poisoning rats were significantly higher than those in control group and treatment group. The expression of two cytokines in the treatment group was higher than that in the control group , But significantly lower than the model group. Conclusions Atorvastatin can inhibit the expression of MMP-9 / TIMP-1 in the lungs of paraquat-poisoned rats and antagonize paraquat-induced pulmonary fibrosis.