鳖甲煎丸缓解博来霉素致大鼠肺纤维化作用初探  

Study on therapeutic effect of Biejiajianwan on bleomycin-induced pulmonary fibrosis in rats

作　　者：师广勇[1] 刘翔[2] 顾丰华[2] 陈嘉[2] 赵绪韬[2] 董文心[2] 

机构地区：[1]郑州大学第五附属医院肿瘤内科,郑州450052 [2]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》2015年第11期743-747,共5页World Clinical Drug

摘　　要：目的评价鳖甲煎丸缓解博来霉素致大鼠肺纤维化的作用。方法 SD雄性大鼠342只,随机分为正常对照组、模型组、阳性对照组及鳖甲煎丸高、中和低剂量组,采用一次性气管内注射博来霉素的方法制备大鼠肺纤维化模型。造模后灌胃给予鳖甲煎丸(一日750、1 500和3 000 mg/kg),以5 mg/kg的泼尼松为阳性对照药物,连续给药1个月后取肺脏,取一半肺组织制备组织匀浆,检测肺脏促纤维化炎性因子TNF-α、TGF-β_1、IL-1β和羟脯氨酸水平(Hyp)及基质金属蛋白酶(MMP)的活性,另一半肺组织采用福尔马林固定后行HE染色和Masson染色,观察肺脏的病理变化和纤维化程度。结果与模型组相比,1阳性对照组、鳖甲煎丸中剂量和高剂量组肺组织中TNF-α、TGF-β_1和IL-1β均有所降低,其中,仅鳖甲煎丸中剂量组TNF-α的降低具有统计学意义(P?0.05);2阳性对照组和鳖甲煎丸各剂量组肺组织Hyp含量均显著减低;3阳性对照组和鳖甲煎丸中剂量组肺组织中MMP活性显著降低,鳖甲煎丸低剂量和高剂量组肺组织中MMP水平无显著变化;4病理组织学检查表明,鳖甲煎丸组肺纤维化病变减轻,炎性细胞浸润受抑,肺组织破坏减轻,肺脏纤维化组织减少,其中以鳖甲煎丸中剂量和高剂量组效果最为显著。结论鳖甲煎丸可能通过抑制肺组织中促纤维化炎性因子TNF-α、TGF-β_1和IL-1β的产生,降低Hyp的水平以及抑制MMP活性等综合因素,抑制肺脏的炎症反应,减轻肺组织的损伤,缓解博来霉素致肺纤维化的程度。Objective To investigate the therapeutic effect of Biejiajianwan on bleomycin-induced pulmonary fibrosis in rats. Methods Three hundred and forty-two SD rats were randomly divided into normal group, model group, prednisone group and therapeutic group. Pulmonary fibrosis model was induced by intratracheal injection with a single dose of bleomycin. Therapeutic groups were treated with Biejiajianwan [750, 1 500 and 3 000 mg/（kg·d）] or prednisone [5 mg/（kg·d）] for one month. After one month treatment, the levels of TNF-α, TGF-β1, IL-1β, hydroxyproline and MMP in lung tissue were measured. Histopathological changes in lung were examined by HE and Masson staining. Results Prednisone and Biejiajianwan could reduce the content of lung tissue inflammatory factors of TNF-α, TGF-β1, IL-1β and the level of hydroxyproline and MMP. Histopathologic examination revealed that Biejiajianwan could relieve bleomycin induced pulmonary fibrosis, inhibit the infiltration of inflammatory cells and alleviate the destruction of lung tissue. Conclusion Biejiajianwan has positive therapeutic effect on pulmonary fibrosis. The possible mechanism is the multiple inhibition of TNF-α, TGF-β1, IL-1β, hydroxyproline and MMP.

关 键 词：鳖甲煎丸 肺纤维化 博来霉素 TNF-α TGF-β1 IL-1β 羟脯氨酸(Hyp) 基质金属蛋白酶(MMPs) 

分 类 号：R979.9[医药卫生—药品] R965[医药卫生—药学]