辛伐他汀对肺纤维化大鼠肺内结缔组织生长因子表达的影响

The Effect of the Simvastatin Administration on the Expression of Connective Tissue Growth Factor in Fibrotic Lungs of Rats

目的观察辛伐他汀对博来霉素引起的肺纤维化大鼠肺内结缔组织生长因子(CTGF)表达的影响。方法大鼠气管内一次性滴注博来霉素复制肺纤维化模型,以等容积生理盐水滴注作为对照。分别在气管内滴注博来霉素当天和7 d后给大鼠辛伐他汀(20 mg/kg)灌胃处理,以等容积的生理盐水灌胃作为对照。分别于7 d、14 d、28 d处死动物,采用HE染色、Masson染色的方法观察肺组织病理变化,通过测定肺组织羟脯氨酸含量观察肺纤维化严重程度,免疫组化和光密度分析观察肺组织CTGF的表达。结果气管内滴注博来霉素后,大鼠肺组织逐渐出现纤维化的病理改变,肺组织CTGF表达明显高于对照组;无论是博来霉素气管内滴注后即刻开始辛伐他汀治疗还是7 d后延迟治疗,在模型建立28 d后,辛伐他汀的治疗均有效地改善了大鼠肺纤维化的严重程度,而且CTGF在肺组织的表达与对照组相比明显减弱。结论无论是辛伐他汀的即刻治疗,还是7 d后延迟治疗,均能有效抑制博来霉素诱导的肺纤维化大鼠肺组织CTGF的高表达,辛伐他汀抑制肺纤维化的作用可能是通过下调CTGF的表达实现的。

Objective To explore the effect of the simvastatin administration on the expression of connective tissue growth factor （CTGF） in fihrotic lungs of rats. Methods The cats were treated with single intratracheal instillation of bleomycin （BLM） or instillation of the same volume of normal saline （NS） as a control. The administration of simvastatin（20 mg/kg）began once a day immediately or 7 days later after intratracheal BLM instillation respectively with the same volume of NS was given as a vehicle control. The rats were killed on day 7,14 and 28 respectively. Pathological alteration of lung tissue was observed hy HE staining and Masson staining. Hydroxyproline（HYP）content in lung tissue was used to determine the severity of pulmonary fibrosis. The expression of CTGF in lung tissue was exanfined by immunohistochem- istry staining and photodeusitometry. Results Histopathological changes of pulmonary fibrosis emerged gradually after the instillation of BLM. The expression level of CTGF was increased in lungs of rats after intratracheal instillation of BLM, compared with the control. The administration of simvastatin immediately or 7 days after intratracheal instillation of BLM, attenuated the histopathological changes of bleomycin- induced puhnonary fibrosis and prevented the increased expression of CTGF in lung tissue on day 28. Conclusion The adntinistration of simvastatin, immediately or 7 days after intratracheal BLM instillation, prevented the up-regulation of CTGF in fibrotic lungs of rats, which ntight be one of the mechanisms of the anti-fihrosis of simvastatin in lungs.