高娟, 李春红. 阿托伐他汀对百草枯中毒损伤肺组织MMP-9及TIMP-1表达的调控[J]. 职业卫生与应急救援, 2015, 33(6): 394-397,438. DOI: 10.16369/j.oher.issn.1007-1326.2015.06.002
引用本文: 高娟, 李春红. 阿托伐他汀对百草枯中毒损伤肺组织MMP-9及TIMP-1表达的调控[J]. 职业卫生与应急救援, 2015, 33(6): 394-397,438. DOI: 10.16369/j.oher.issn.1007-1326.2015.06.002
GAO Juan, LI Chunhong. Effects of atorvastatin on matrix metalloproteinase-9 and matrix metalloproteinase inhibitor-1 in lung injury caused by paraquat[J]. Occupational Health and Emergency Rescue, 2015, 33(6): 394-397,438. DOI: 10.16369/j.oher.issn.1007-1326.2015.06.002
Citation: GAO Juan, LI Chunhong. Effects of atorvastatin on matrix metalloproteinase-9 and matrix metalloproteinase inhibitor-1 in lung injury caused by paraquat[J]. Occupational Health and Emergency Rescue, 2015, 33(6): 394-397,438. DOI: 10.16369/j.oher.issn.1007-1326.2015.06.002

阿托伐他汀对百草枯中毒损伤肺组织MMP-9及TIMP-1表达的调控

Effects of atorvastatin on matrix metalloproteinase-9 and matrix metalloproteinase inhibitor-1 in lung injury caused by paraquat

  • 摘要: 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。

     

    Abstract: Objective To explore the effects of atorvastatin on lung injury induced by paraquat and on matrix metalloproteinases (MMPs) and their inhibitors(TIMPs). Methods A total of 45 male Wister rats were randomly divided into control group, PQ treated group,and atorvastatin treatment group(15 in each group).The rats in the PQ group and the treatment group were given paraquat 50 mg/kg orally; the rats in the treatment group received atorvastat in 20 mg/kg. the animals were dissected in batches (on the 7th, 14th and 28th day)and related samples were collected. The pathology of lung tissue was studied.The levels of MMP-9 and TIMP-1 in the lung tissue were measured by immunohistochemistry, RT-PCR and Western-blot. The levels of MMP-9 and TIMP-1 in fibrocyte were detected by RT-PCR. The levels of MMP-9 and TIMP-1 in Serum were detected by ELISA. Results Lung injury was obvious in PQ treated group, while it was less serious in the atorvastatin treatment group. The expression level of MMP-9 and TIMP-1 were higher in the atorvastatin treatment compared with that of the control group, but lower than that in PQ treated group. The serum MMP-9 level was the highest in the alveoli inframammary stage (day 7), and declined with time (day 14 and 28), while all were higher than that in atorvastatin treatment group. In the same phase, there were no significant difference of serum TIMP-1 level among the three groups(P>0.05). The expression levels of MMP-9 and TIMP-1 of lung fibroblasts in atorvastatin treatment group were lower compared with those of PQ treated group and higher than those in control group. Conclusion Atorvastatin could alleviate lung injury induced by PQ in rats by preventing the secretion of MMP-9 in the lung while has no effect on the serum level of MMP-9 and TIMP-1.

     

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