慢性阻塞性肺疾病合并慢性肾病大鼠模型建立与评价

Model establishment and evaluation of chronic obstructive pulmonary disease complicated with chronic kidney disease in rats

目的 建立与评价慢性阻塞性肺疾病(COPD)合并慢性肾病(CKD)大鼠模型。方法 将40只雌雄各半SPF级SD大鼠随机分为对照组(Control组)、COPD组、CKD组、COPD合并CKD模型组(COPD+CKD组),每组10只。采用香烟烟雾暴露联合细菌滴注法制备COPD大鼠模型,利用腺嘌呤诱导建立CKD大鼠模型,两种方法协同制备COPD合并CKD的大鼠模型,8周后取材检测肺、肾功能,观察组织形态学及血清炎症因子的表达水平。结果 造模成功后COPD+CKD组大鼠肺功能指标FVC、FEV_(0.1)及FEV_(0.1)/FVC显著降低(P<0.01),肺组织病理学表现为肺泡壁断裂、融合的肺气肿改变及炎细胞浸润;血Cr、BUN及24 h尿蛋白显著升高(P<0.01),肾组织病理学表现为肾小球系膜增生,基底膜增厚,肾小管扩张及间质纤维化,超微结构显示肾小球毛细血管襻部分闭合,足突融合,肾小管线粒体融合崩解,溶酶体增多;血清IL-6、IL-13、IL-1β和TGF-β1水平显著升高(P<0.01),且明显高于单一模型组(P<0.01)。结论 采用香烟烟雾暴露联合细菌感染合并2.5%腺嘌呤诱导的方法可成功构建COPD合并CKD的大鼠模型,炎性反应可能在COPD合并CKD过程中起关键作用。

Objective To establish and evaluate a model of chronic obstructive pulmonary disease(COPD)combined with chronic kidney disease(CKD)in rats.Methods Forty SPF grade SD rats were randomly divided into Control group,COPD group,CKD group,and COPD combined with CKD model(COPD+CKD)group,with 10 rats in each group.The COPD rat model was prepared by cigarette smoke exposure combined with the bacterial drip method,the CKD rat model was established by adenine induction,and the COPD combined with CKD rat model was prepared by both method.Results After successful modeling,lung function indexes incluidng forced vital capacity(FVC),forced expiratory volume in 01 s(FEV01),and FEV01/FVC were significantly reduced in the COPD+CKD group(P<001),and lung histopathology showed emphysematous changes with alveolar wall fracture and fusion as well as inflammatory cell infiltration.Serum Cr,BUN,and 24 h urine protein were significantly increased(P<001).Renal histopathology showed glomerular mesentery proliferation,basement membrane thickening,tubular dilatation,and interstitial fibrosis.The ultrastructure showed that glomerular capillary loops were partially closed,foot processes were fused,renal tubule mitochondria were fused and disintegrated,and lysosome was increased.Serum IL-6,IL-13,IL-1β,and TGF-β1 levels were significantly increased(P<001)and were significantly higher than those in single model groups(P<001).Conclusions Cigarette smoke exposure combined with bacterial infection and 25%adenine induction successfully establishes a model of COPD complicated with CKD in rats,and the inflammatory response might play a major role in the process of COPD complicated with CKD.