丹贝益肺汤对博来霉素诱导肺纤维化大鼠肺纤维化及肺血管重塑的影响

Effects of Danbei Yifei Decoction(丹贝益肺汤)on Pulmonary Fibrosis and Pulmonary Vascular Remodelingin of Rats with Pulmonary Fibrosis Induced by Bleomycin

目的:研究丹贝益肺汤对博来霉素(bleomycin,BLM)诱导的特发性肺纤维化及肺血管重塑的影响。方法:SD大鼠随机分为正常对照组、模型组、阳性对照组(甲泼尼龙,4.2 mg/kg)和丹贝益肺汤高(15.2 g/kg)、中(7.6 g/kg)、低剂量(3.8 g/kg)组,每组20只。除正常组外,其余各组均采用雾化吸入BLM诱导肺纤维化,成模后连续灌胃给药20 d。取各组大鼠肺组织行HE、Masson染色,光镜观察肺组织炎性改变及纤维化程度;ELISA检测血清内皮型一氧化氮合酶(eNOS)、内皮素-1(ET-1)和血管性血友病因子(vWF)水平。结果:与模型组比较,各给药组大鼠肺组织炎性改变和纤维化程度明显减轻,丹贝益肺汤高剂量组肺组织炎性改变和纤维化程度与阳性组接近。ELISA检测结果显示各给药组eNOS水平明显增高,血管增生指标ET-1、vWF水平均明显下降(P均<0.05);其中高剂量组上述指标变化显著于阳性组(P均<0.05)。结论:丹贝益肺汤可剂量依赖性减轻BLM诱导的大鼠肺纤维化程度,提高血清eNOS水平,抑制ET-1、vWF表达,调节肺血管重塑是其部分作用机制。

Objective:To study the effects of Danbei Yifei Decoction on pulmonary fibrosis and pulmonary vascular remodeling in rats with bleomycin-induced idiopathic pulmonary fibrosis.Methods:SD rats were randomly divided into normal control group,model group,positive control group(methylprednisolone,4.2 mg/kg)and Danbei Yifei Tang High(15.2 g/kg),middle(7.6 g/kg),low dose(3.8 g/kg)groups with 20 rats in each group.Except the normal group,all the other groups were induced by aerosol inhalation of BLM for 7 days,each group was given the corresponding medicine or saline for 20 days.The lung tissue of each group was stained with HE and Masson,and the inflammatory changes and the degree of fibrosis were observed under light microscope,serum levels of endothelial nitric oxide synthase(eNOS),endothelin-1(ET-1)and von willebrand disease factor(vWF)were measured by ELISA.Results:Compared with the model group,the inflammatory changes and the degree of pulmonary fibrosis in each medication group were obviously alleviated,and the inflammatory changes and the degree of pulmonary fibrosis in the high-dose group were similar to those in the positive group.The results of ELISA showed that the levels of eNOS were significantly increased and the levels of ET-1 and vWF were significantly decreased in every medication group(P<0.05),and the changes of the above-mentioned indexes in the high-dose group were significantly higher than those in the positive group(P<0.05).Conclusion:Danbei Yifei Decoction can reduce the degree of pulmonary fibrosis induced by BLM in a dose-dependent manner,increase the level of eNOS in serum,inhibit the expressions of ET-1 and vWF,and regulate the remodeling of pulmonary vessels.