从溃疡性结肠炎大鼠肺损伤细胞凋亡机制探讨“肺与大肠相表里”

Discussion on theory of the lung and the large intestine being interior-exteriorly related from mechanism of apoptosis in lung injury in rats with ulcerative colitis

目的:探讨溃疡性结肠炎(ulcerative colitis,UC)大鼠肺损伤的细胞凋亡机制,进一步探究"肺与大肠相表里"理论.方法:66只Wistar大鼠,随机分为6组,3个观察时间点均设正常组与模型组,其中正常组均为10只,模型组均为12只,模型组大鼠采用结肠黏膜组织致敏加三硝基苯磺酸-50%乙醇灌肠的方法建立大鼠UC模型,于造模后第0、2、4周动态观察肺、结肠组织病理形态学改变,采用Western blot法动态观察大鼠肺组织中Bcl-2、Bax蛋白表达变化.结果:与正常组比较,各时间点模型组大鼠肠质量指数明显升高(第0周:0.00252±0.000557 vs 0.00564±0.00119,P=0.0000;第2周:0.00245±0.000234 vs 0.00573±0.00283,P=0.0002;第4周:0.00237±0.000284 v s0.00524±0.00310,P=0.0014)、肺质量指数增加(第0周:0.00404±0.000399 vs 0.00473±0.000634,P=0.0088;第2周:0.00383±0.000433 vs 0.00472±0.00104,P=0.0267;第4周:0.00347±0.000444 vs 0.00440±0.00106,P=0.0017),肺肠组织HE染色均出现明显病理变化,肺组织Bcl-2蛋白表达水平明显下降(第2周:1.333±0.114 vs 0.947±0.068,P=0.0072;第4周:1.594±0.187 vs 0.982±0.128,P=0.0094),Bax蛋白表达水平明显上升(第2周:0.521±0.069 vs 1.078±0.220,P=0.0139;第4周:0.817±0.179 vs 1.491±0.323,P=0.034),Bcl-2/Bax比值显著降低(第2周:2.570±0.147vs 0.895±0.129,P=0.0001;第4周:2.036±0.586 vs 0.668±0.0678,P=0.016).结论:肺组织中Bcl-2和Bax蛋白表达异常并诱导肺组织细胞凋亡可能是UC肺损伤的分子机制之一,并可能为"肠病及肺"提供理论依据.

AIM：To discuss mechanism of apoptosis of in lung injury in rats with ulcerative colitis and to further explore the theory of the lung and the large intestine being interior-exteriorly related.METHODS：Sixty-six Wistar rats were randomly divided into two groups：normal group and model group.Both groups were observed at three time points（10 rats at each time pointfor the normal group,and 12 rats for the model group）.The model was established using immune complex and trinitrobenzenesulfonic acid.Pathological and morphological changes of the lung and the colon were dynamically observed on the 0,2 nd and 4 th wk.Protein expression of Bcl-2 and Bax in the lung was tested by Western blot.RESULTS：Compared to the normal group,intestinal index（week 0：0.00252±0.000557 vs 0.00564±0.00119,P=0.0000;week 2：0.00245±0.000234 vs 0.00573±0.00283,P=0.0002;week 4：0.00237±0.000284 vs 0.00524±0.00310,P=0.0014） and lung index（week 0：0.00404±0.000399 vs 0.00473±0.000634,P=0.0088;week 2：0.00383±0.000433 vs 0.00472±0.00104,P=0.0267;week 4：0.00347±0.000444 vs 0.00440±0.00106,P=0.0017） significantly increased in the model group at various time points.Compared to the normal group,obvious pathological changes appeared in the lung and the colon and there were decreased expression of Bcl-2（week 2：1.333±0.114 vs 0.947±0.068,P=0.0072;week 4：1.594±0.187 vs 0.982±0.128,P=0.0094） and Bax（week 2：0.521±0.069 vs 1.078±0.220,P=0.0139;week 4：0.817±0.179 vs 1.491±0.323,P=0.034） and significantly reduced ratio of Bcl-2 to Bax（week 2：12.570±0.147 vs 0.895±0.129,P=0.0001;week 4：2.036±0.586 vs 0.668±0.0678,P=0.016）.CONCLUSION：Abnormal expression of Bcl-2 and Bax in the lung that induces cell apoptosis may be one of molecular mechanisms of lung injury in ulcerative colitis and may provide a theoretical basis for enteropathy inducing pneumonopathy.