鳖甲煎丸对百草枯致大鼠肺纤维化的改善作用研究  

Therapeutic effect of Biejiajianwan on paraquat-induced rat pulmonary fibrosis

作　　者：刘翔[1] 陈嘉[1] 顾丰华[1] 赵绪韬[1] 董文心[1] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室,上海200437

出　　处：《世界临床药物》2016年第3期160-165,198,共7页World Clinical Drug

基　　金：上海市生物物质成药性评价专业技术服务平台(编号:15DZ2291700)

摘　　要：目的探讨鳖甲煎丸对百草枯致大鼠肺纤维化的改善作用。方法本研究共设6组(正常对照组、模型组、阳性对照组以及鳖甲煎丸高、中和低剂量组),除正常对照组(n=10)外,其余各组大鼠均采用百草枯药液腹腔注射致肺纤维化。造模第2天,鳖甲煎丸各剂量组按高、中和低剂量(3.0、1.5和0.75 g/kg)经口灌胃给予鳖甲煎丸,阳性对照组经口灌胃泼尼松(5 mg/kg),均连续给药30 d。给药结束观察大鼠存活情况,处死大鼠并摘取肺脏称重计算其脏器系数;取一半肺组织制备组织匀浆,检测肺脏促纤维化炎性因子如转化生长因子(TGF)-β1、肿瘤坏死因子(TNF)-α和白介素(IL)-1β的含量,以及基质金属蛋白酶(MMP)活性和羟脯氨酸(Hyp)水平;另一半肺组织经福尔马林固定后行HE染色和Masson染色,观察肺脏的病理变化和纤维化程度。结果 1模型组大鼠存活率为36.7%,阳性对照组和鳖甲煎丸3.0 g/kg剂量组存活率分别为54.5%和63.6%,均显著高于模型组(P<0.01,P<0.05);2与模型组比较,阳性对照组和鳖甲煎丸3.0 g/kg剂量组肺脏重量显著减轻(P<0.05);3与模型组比较,鳖甲煎丸1.5和3.0 g/kg剂量组TNF-α、TGF-β1和IL-1β含量显著降低,鳖甲煎丸各剂量组MMP和Hyp水平下降(P<0.01,P<0.05);4病理组织学检查显示,与模型组比较,鳖甲煎丸3.0 g/kg剂量组大鼠肺脏破坏程度和肺纤维化病变明显减轻。结论鳖甲煎丸可改善肺纤维化大鼠肺部损伤和肺纤维化症状,可能通过抑制肺组织中促纤维化炎性因子TNF-α、TGF-β1和IL-1β分泌,降低MMP活性和Hyp含量等发挥抗肺纤维化作用。Objective To investigate the therapeutic effects of Biejiajianwan on paraquat-induced pulmonary fibrosis in rats. Methods There were six groups including normal control group, model group, prednisone group and Biejiajianwan in high, middle and low dose groups. Except normal control group（n=10） the rats in each group were induced by intraperitoneal injection of paraquat. From the second day, the rats in therapeutic group were treated with Biejiajianwan at 0.75, 1.5, 3.0 g/kg or prednisone at 5 mg/kg peros for 30 days. After treatment, the survival rats were observed. After rats were killed, the lung weight and the organ coefficient were calculated. The levels of TNF-α, TGF-β1, IL-1β, hydroxyproline（Hyp） and matrix metalloproteinase（MMP） in lung tissues were measured. Histopathological changes of lung were examined by HE and Massion staining.Results① Prednisone and 3.0 g/kg Biejiajianwan could improve the survival rate of the rats（54.5% and 63.6% respectively）, which were significantly higher than that of the model group（P〈0.01, P〈0.05）. ② Prednisone and 3.0 g/kg Biejiajianwan inhibited the lung inflammatory swelling, reduced the absolute weight of the lung significantly than that in model group（P〈0.05）. ③ 1.5 and 3.0 g/kg Biejiajianwan significantly decreased the content of TNF-α, TGF-β1, IL-1β in lung tissue, and Biejiajianjiawan significantly reduced MMP activity and the content of Hyp in each dose group（P〈0.01, P〈0.05）. ④ Histopathological examination showed that Biejiajianwan could relieve the paraquat-induced pulmonary fibrosis, inhibit the infiltration of inflammatory cells, and alleviate the destruction of lung tissue especially in the group of 3.0 g/kg Biejiajianwan. Conclusion Biejiajianwan can inhibit TNF-α, TGF-β1, IL-1β, MMP and Hyp, and has the positively therapeutic effect on pulmonary fibrosis.

关 键 词：鳖甲煎丸 肺纤维化 百草枯 肿瘤坏死因子(TNF)-α 转化生长因子(TGF)-β1 白介素(IL)-1β 羟脯氨酸(Hyp) 基质金属蛋白酶(MMP) 

分 类 号：R965.2[医药卫生—药理学]