作 者 ：金晓滢,骆仙芳,宋康,夏永良,单建贞,孙永梅
期 刊 ：中国中药杂志 2009年 34卷 12期 页码：1574.
关键词：虎杖；大鼠；肺纤维化；肺成纤维细胞；基质金属蛋白酶；
Keywords:Huzhang, rats, Pulmonary fibrosis, lung fibroblast, matrix metalloproteinase,
摘 要 ：目的：观察虎杖对大鼠肺纤维化形成的影响，并探讨其作用机制。方法：将雄性SD大鼠随机分成正常对照组、模型组、阳性对照组、虎杖预防组、 虎杖3 d治疗组、7 d治疗组和14 d治疗组。除正常对照组外其余各组均气管内注射博莱霉素诱导肺纤维化。阳性对照组造模当天予0.5%地塞米松4 mL·kg-1·d-1灌胃；正常对照组和模型组于造模后当天开始灌胃生理盐水4 mL·kg-1·d-1；虎杖预防组、虎杖3，7，14 d治疗组分别在造模前2 d、造模后第3，7，14天开始胃饲受试药物4 mL·kg-1·d-1(含生药量1 g·mL-1)，进行动态观察。HE，Masson染色行肺组织病理学检查，胰酶消化法行肺成纤维细胞培养，并用RT-PCR法检测MMP-2，TIMP-1mRNA的表达。结果：与模型组比较，阳性对照组、虎杖预防组及各治疗组，肺泡炎、肺纤维化程度及胶原沉积均明显减轻。肺成纤维细胞MMP-2mRNA表达除第42天与模型组相似，无统计学意义，其余之前的时间点均较模型组减弱(P<0.05或P<0.01)；TIMP-1mRNA表达也均较模型组减弱(P<0.05或P<0.01)，其持续抑制时间更长，直至第42天。结论：虎杖通过抑制不同时期肺成纤维细胞MMP-2，TIMP-1mRNA的异常高表达以减轻肺泡炎及肺纤维化的程度，可能是其延缓肺纤维化的作用机制之一。
Abstract:Objective: To observe the effect of Huzhang on the progress of pulmonary fibrosis in rats, evaluate the role of Huzhang in this process and explore its mechanism. Method: Wistar male rats were randomized into 7 groups (normal control group, model group, positive control group, prophylactic group, 3 rd day treatment group, 7 rd day treatment group and 14 rd day treatment group). Bleomycin was administered by intratracheal injection to produce pulmonary fibrosis groups except the normal control group. The positive control group began to be given DXM (4 mL·kg-1·d-1) on the day of the model-making. The normal control group and model group were given NS (4 mL·kg-1·d-1) on the day of the model-making. The prophylactic group was given reagent (4 mL·kg-1·d-1) 2 days ahead of the model-making, whereas the 3 rd day treatment group, the 7 th day treatment group and the 14 th day treatment group given the same dose respectively on the third day, the seventh day and the fourth day behind of the model-making. Lung tissue was stained with hematoxylin-eosin (HE) and Masson‘s trichrome to determine the pathological grading. The lung fibroblast (LF) was cultured in vitro by way of pancreatic enzyme digestion, which was used to detect the contents of the expression of MMP-2 and TIMP-1mRNA with RT-PCR method. Result: Compared with those in the model group, the alveolitis, pulmonary fibrosis and collagen accumulation were significantly alleviated in the positive control group, Huzhang prophylactic group and each treatment groups. In the positive control group, Huzhang prophylactic group, the3 rd day treatment group, the 7 th day treatment group and the14 th day treatment group ,the expression of MMP-2 mRNA was weaker significantly than that in the BLM model group (P<0.05 or P<0.01) except that on the 42 nd day. The expression of TIMP-1mRNA was also weaker significantly than that in the BLM model group at all set times in all treatment groups (P<0.05 or P<0.01). The inhibition of TIMP-1 lasted until the 42 nd day. Conclusion: Huzhang inhibited the expression of MMP-2mRNA and TIMP-1mRNA of lung fibroblast in different periods to reduce the alveolitis and pulmonary fibrosis, which was probably one of the anti-fulmonary fiborsis mechanisms of Huzhang.