Caspase抑制剂早期干预对吸烟型肺气肿大鼠肺泡结构保护的实验研究

Protective effects of Caspase inhibitor z-VAD-fmk on pulmonary alveoli structure in smoke-induced emphysema rats

目的:探讨早期使用Caspase抑制剂z-VAD-fmk对吸烟型肺气肿大鼠肺泡结构保护的机制。方法:30只清洁级SD大鼠平均随机分为对照组(A组)和肺气肿模型组(B组)和z-VAD-fmk干预组(C组)。12周后取肺组织制作石蜡切片,光镜下观察肺泡病理改变。原位缺口末端标记法(TUNEL)检测各组大鼠肺泡隔细胞凋亡指数(apoptosis index,AI),免疫组化检测肺组织中Bcl-2和Bax蛋白的表达情况。结果:12周末光镜显示:B组较C组肺气肿特征性病理改变逐渐加重,A组无肺气肿表现。各组肺泡隔细胞AI,B组与A、C组相比差异有统计学意义(P<0.05)。免疫组化显示B组Bax蛋白表达呈强阳性,而Bcl-2蛋白表达相对较弱,与A、C组比较差异有统计学意义(P<0.05)。结论:肺气肿形成初期,使用Caspase-3抑制剂z-VAD-fmk可显著上调肺组织中Bcl-2蛋白表达,抑制Bax蛋白的表达,使肺泡隔细胞凋亡减少,明显减轻肺气肿的病理改变。

Objective： To investigate the mechanism of using caspase inhibitor z-VAD-fmk to protect the pulmonary alveoli structure in early stage of COPD.Methods： 30 Sprague-Dawley（SD） rats were randomly divided into three groups of 10 rats each： normal control group（A group）,smoke-induced COPD group（B group） and z-VAD-fmk treatment group（C group）.The rat lung tissues of 3 groups were embedded in paraffin 12 weeks later.Histopathological changes were observed by HE.TdT-mediated X-dUTP nick end labeling（TUNEL） was applied to analyze and apoptosis index（AI） was obtained.Immunohistochemistry was also applied to observe the expression of Bcl-2 and Bax.Results： 12 weeks later,there were specific pathognomonic features in B group.However,these pathognomonic features were attenuated in C group.The AI in B group was higher than that in A and C group（P0.05）.Immunohistochemistry showed： Bcl-2 and Bax were expressed in lung tissue of B group,and were higher than those in A and C groups（P0.05）.The expression of Bcl-2 was significantly increased after using caspase inhibitor z-VAD-fmk,but the expression of Bax was inhibited.Conclusion： In the early stage of COPD,using z-VAD-fmk can attenuate the pathognomonic features of emphysema.