苦参碱减轻博来霉素致大鼠肺纤维化

Matrine alleviates blemycin-induced pulmonary fibrosis in rats

目的观察苦参碱对博来霉素诱导的肺纤维化大鼠的保护作用,并探讨其可能的分子机制。方法大鼠随机分为对照组、模型组、泼尼松和苦参碱处理组。模型组气管内给予博莱霉素(5 mg/kg)建立肺纤维化动物模型。建模后第1天起,分别每日予以泼尼松(0.56 mg/kg)和不同剂量的苦参碱(50和100 mg/kg)灌胃1次。于第7、14和28天时,获取大鼠取肺组织并行HE和Masson染色。检测肺纽织匀浆中丙二醛(MDA)和羟脯氨酸(HYP)含最;RT-PCR法检测肺组织血红素氧合酶(HO-1)mRNA的表达;ELISA检测TNF-α产生。结果HE染色显示,模型组7 d以炎性反应为主,28 d可见大量的肺成纤维细胞,Masson染色见有更多胶原沉积。而苦参碱与泼尼松能明显减轻其炎性反应和纤维化程度。模型组中MDA和HYP含量较对照组显著增高(P<0.05),而予以苦参碱及泼尼松干预以后,二者含量均有下降,以28 d时改变最明显(P<0.05)。在正常肺组织中,HO-1处于低表达状态,TNF-α含量低。而模型组二者的含最明显上升(P<0.01),苦参碱干预后,两者表达水平显著降低(P<0.05)。结论苦参碱具有减轻肺纤维化形成的作用,其机制可能与调节机体氧化-抗氧化失衡,抑制TNF-α的产生以及下调HO-1的表达水平有关。

Objective To discuss the molecular mechanism and protective effect of matrine on blemycin-induced pulmonary fibrosis rat. Methods Rats were randomly divided into five groups, the control group, model group, prednisone, matrine low dose and high dose group. Pulmonary fibrosis model was made by adminstrated blecomin （5 mg/kg） through trachea. From 1st day after modeling, the rats were fed prednisone acetate （0.56 mg/kg/d） or different dose matrine （50 and 100 mg/kg/d）. At the 7, 14, 28 days of modeling, the lung tissue biopsy sections are observed by HE and Masson staining pathology. The malondialdehyde （MDA） level and hydroxyproline （HYP） content in lung tissue was detected, HO-1 mRNA was measured by RT-PCR, and by production of TNF-α. The lung tissue biopsy sections are detected by HE and Masson staining pathology. Results In model group, in-flammatory response was the main event at 7 d. At 28 d, more lung fibroblast were found. The collagen was found more clearly. Pathological change in the matrine and prednisone treated group was less than that from model group. The MDA and HYP content in model group was higher as compared with normal control group （ P 〈 O. 05 ） , and de- creased after matrine and prednisone treatment in 28 d （P 〈0.05 ）. In the normal lung tissue, expression of HO-1 and production of TNF-α was very low, and increased in the model group. After drug intervention, the level of both TNF-α and HO-1 was decreased （ P 〈 0.05 ）. Conclusions Matrine can alleviate the fibrosis status in rats, and the mechanism may be associated to regulate oxidative-antioxidant imbalance and inhibition of TNF-α and HO-1 ex- pression.