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目的研究阿托伐他汀对大鼠百草枯中毒所致肺损伤的保护作用及其对基质金属蛋白酶(MMPs)及其抑制剂(TIMPs)的影响。方法取45只雄性Wister大鼠,随机数字表法分为对照组、染毒组、治疗组,每组各15只。染毒组及治疗组均以百草枯50 mg/kg灌胃建立大鼠肺纤维化模型;治疗组每日给予阿托伐他汀20 mg/kg。分组后分别于灌胃7、14、28 d后观察大鼠一般情况并解剖,取肺组织行苏木精-伊红(HE)染色,光镜观察。用免疫组化、RT-PCR、Western-blot等方法检测肺组织中MMP-9及TIMP-1水平。用RT-PCR法检测肺组织成纤维细胞中MMP-9及TIMP-1水平。用ELISA法检测血清中MMP-9及TIMP-1水平。结果 HE染色结果显示,染毒组有明显的肺损伤,治疗组肺损伤较染毒组减轻。治疗组肺组织中MMP-9、TIMP-1表达量高于正常对照组,但低于染毒组。染毒组动物血清中的MMP-9的浓度在肺泡炎症阶段(7 d)最高,14 d、28 d后呈下降趋势,但均高于治疗组。治疗组血清中的MMP-9的浓度低于染毒组,但差异无统计学意义(P>0.05),相同时段三组TIMP-1浓度比较,差异均无统计学意义(P>0.05)。各组动物肺组织成纤维细胞中,治疗组表达量低于染毒组,高于对照组。结论阿托伐他汀具有抑制百草枯中毒大鼠肺内MMP-9、TIMP-1的表达上调的作用。阿托伐他汀对血液中系统分泌的MMP-9、TIMP-1的浓度无显著影响。
Objective To investigate the protective effect of atorvastatin on lung injury induced by paraquat and its effect on matrix metalloproteinases (MMPs) and its inhibitors (TIMPs) in rats. Methods 45 male Wister rats were randomly divided into control group, exposure group and treatment group, 15 in each group. Rats in the treatment group and the treatment group were given paraquat 50 mg / kg by intragastric administration to establish the rat model of pulmonary fibrosis; the treatment group was given daily atorvastatin 20 mg / kg. After the rats were grouped, the rats were observed on the 7th, 14th and 28th days after gavage respectively. The lungs were stained with hematoxylin and eosin (HE) and observed with light microscope. The levels of MMP-9 and TIMP-1 in lung tissue were detected by immunohistochemistry, RT-PCR and Western-blot. The levels of MMP-9 and TIMP-1 in lung tissue fibroblasts were detected by RT-PCR. Serum levels of MMP-9 and TIMP-1 were detected by ELISA. Results The results of HE staining showed that there was obvious lung injury in the treated group and lung injury in the treated group was less than that in the treated group. The expression of MMP-9 and TIMP-1 in the lung tissue of the treatment group was higher than that of the normal control group, but lower than that of the exposure group. The concentration of MMP-9 in sera from the exposed group was the highest at the stage of alveolar inflammation (7 d), and then decreased after 14 d and 28 d, but both were higher than the treatment group. The serum concentration of MMP-9 in the treatment group was lower than that in the control group, but the difference was not statistically significant (P> 0.05). There was no significant difference in the TIMP-1 concentration between the three groups at the same time point (P> 0.05). In each group of animal lung tissue fibroblasts, the expression of the treatment group was lower than the exposure group, higher than the control group. Conclusions Atorvastatin can inhibit the up-regulation of MMP-9 and TIMP-1 in paraquat poisoning rats. Atorvastatin had no significant effect on the systemic secretion of MMP-9 and TIMP-1 in blood.