中药丹芍化纤胶囊对博来霉素致肺纤维化大鼠Smad7表达的影响

Effects of the Traditional Chinese Medicine Prescription,Dan- Shao- Hua- Xian Capsules,on expression of Smad7 in bleomycin- induced rat pulmonary fibrosis

目的观察博来霉素致肺纤维化大鼠肺组织中Smad7表达的变化及中药丹芍化纤胶囊对其表达的影响。方法 SD大鼠30只,随机分为正常对照组(正常组)、肺纤维化模型组(模型组)、丹芍化纤胶囊预防性治疗组(丹芍组),每组各10只。正常对照组气管内滴注生理盐水,模型组和丹芍组一次性滴注博来霉素5mg/kg诱导肺纤维化,丹芍组于造模第2天给予丹芍化纤胶囊混悬液灌胃(0.8 g/kg)治疗。实验第28天处死各组大鼠,计算肺系数,行HE和Masson染色观察肺组织病理变化;检测肺组织中HYP、MDA、SOD含量;采用免疫组织化学方法检测Smad7蛋白的表达情况,运用实时荧光定量PCR(qRT-PCR)的方法检测各组大鼠肺组织中Smad7mRNA的表达变化。结果与正常组比较,肺纤维化模型组大鼠肺系数、肺HYP、MDA含量明显增高,SOD活性降低,肺组织中Smad7蛋白表达降低,且Smad7mRNA的表达也显著降低;与模型组相比,丹芍组大鼠肺系数、肺HYP及MDA含量明显降低,SOD活性增强,肺组织中Smad7蛋白和mRNA表达较模型组显著提高。结论 Smad7在大鼠肺纤维化的发生发展中有明显作用,丹芍化纤胶囊早期应用能预防和减缓博来霉素致大鼠肺纤维化的进展,其干预肺纤维化的机制可能与上调肺组织中Smad7的表达有关。这可能是丹芍化纤胶囊抗肺纤维化的作用机制之一;Smad7可能是丹芍化纤胶囊作用的一个药物靶点。

Objective To investigate the effect of Dan - Shao - Hua - Xian Capsules （DSHX） on the expression of Smad7 in blemycin - induced rat pulmonary fibrosis. Methods Thirty Spagne - Dawley rats were randomly divided into three groups ： normal control group（ control group ）, blemycin - induced rat pulmonary fibrosis group （ model group ）, DSHX - treated group （ DSHX group）. Rats in both model group and DSHX -treated group were induced by dripping blemycin （5 mg ~ kg- 1 ） endotracheally, while the rats of control group was given 0.9% saline instead. From the second day of injection, the rats in the DSHX group were treated with DSHX capsule （0.8g ~ kg- 1 ） through p. o everyday once for 4 weeks, while the other rats were given O. 9% saline in- stead. All rats were killed on the twenty - eighth day. The rat lung histopathology was examined with HE and Masson staining. The lung coefficient and lung hydroxyproline （Hyp） were evaluated. Immunohistochemical and qRT -PCR techniques were applied to detect the both protein and mRNA expression of SmadT. Results Compared with control group, the lung coefficient, HYP and MDA content were significantly increased, while the content of SOD and the expression of Smad7 in both of protein and mRNA lev- els were decreased. After 4 weeks DSHX treatment, the lung coefficient, HYP and MDA content were significantly decreased, while the content of SOD and the expression of Smad7 in both of protein and mRNA levels were significantly increased. Conclusion S- mad7 has an important role in the progress of experimental rats of pulmonary fibrosis. Dan - Shao - Hua - Xian Capsule has a good action to prevent and ameliorate the process of bleomyein - induced rat pulmonary fibrosis, which may happen through improving the expression of SmadT. This might be one of the mechanisms of how Dan - Shao - Hua - Xian＇s inhibiting pulmonary fibrosis process, and Smad7 might be its potential target.