2型糖尿病肺脏超微结构变化及TLR2/4表达的实验研究  

Ultrastructural changes and Toll-like receptor mRNA expression in type 2 diabetic lung tissue

作　　者：沈兴平[1] 李娟[1] 陈守惠[1] 殷平[1] 

机构地区：[1]厦门大学附属中山医院内分泌科,361004

出　　处：《免疫学杂志》2012年第12期1040-1044,共5页Immunological Journal

基　　金：厦门市科技计划项目(3502Z20084017);厦门市第三周期医学重点学科建设项目;福建省自然科学基金资助项目(X0750055)

摘　　要：目的观察2型糖尿病大鼠早期肺脏超微结构变化及TLR2/4样受体表达状况,探讨糖尿病易并发呼吸道感染的机制。方法采用电子显微镜、免疫组织化学及逆转录-聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)方法,观察2型糖尿病大鼠早期肺脏超微结构变化及TLR2/4样受体表达。结果 2型糖尿病大鼠2周时见肺泡上皮细胞及毛细血管内皮细胞间基板轻度增厚;4周时见粗面内质网轻度扩张,8周时较多Ⅱ型肺泡上皮细胞核固缩、线粒体和板层小体空泡化、粗面内质网扩张明显。糖尿病大鼠2周时,TLR4在支气管纤毛上皮、血管内皮细胞和平滑肌细胞表达,8周时在细支气管肺泡上皮、肺泡上皮及血管平滑肌细胞均有表达,糖尿病2周起肺组织TLR4及mRNA表达水平明显高于对照组(P<0.05)。糖尿病大鼠4周时,TLR2在大鼠肺细支气管肺泡上皮表达,8周时在血管内皮细胞明显表达,糖尿病6周起肺组织TLR2及mRNA表达水平明显高于对照组(P<0.05)。结论早期2型糖尿病大鼠肺脏存在超微结构改变和TLR2/4样受体表达异常,可能与2型糖尿病易并发呼吸道感染有关。We aimed to observe the early changes in lung ultrastructure and TLR2/4 expression in type 2 diabetic rats and to explore the mechanism underlying their predisposition to respiratory tract infections.By using electron microscopy,immunohistochemistry,and reverse transcription-polymerase chain reaction（RT-PCR）,we observed a mild thickening of the basal lamina between the alveolar epithelial cells and capillary endothelial cells 2 weeks after the onset of diabetes.Four weeks after the onset,mild dilation of rough endoplasmic reticulum was observed;eight weeks after the onset,shrinkage of the nuclei,vacuolation of the mitochondria and lamellar bodies,and dilation of the rough endoplasmic reticulum were observed.On the other hand,TLR4 expression was detected in ciliated bronchial epithelial cells,vascular endothelial cells,and smooth muscle cells 2 weeks after the onset of diabetes.And 8 weeks after the onset,TLR4 expression was detected in bronchiolar-alveolar epithelium,alveolar epithelium and vascular smooth muscle cells.Starting from 2ed week after the onset of diabetes,levels of TLR4 protein and mRNA were significantly higher in the lungs of affected rats than those in those of control rats（P 0.05）.Four weeks after the onset of diabetes,TLR2 expression was detected in bronchiolar-alveolar epithelium.Eight weeks after the onset,significant high expression of TLR2 was detected in vascular endothelial cells.Starting from 6th week,levels of TLR2 protein and mRNA level were significantly higher in the lungs of control rats than those of control rats（P 0.05）.From all the result,we get a conclusion that early changes in ultrastructure and abnormal expression of TLR2/4 are existed in the lungs of diabetic rats,which may contribute to the predisposition to respiratory tract infections.

关 键 词：糖尿病 肺脏 TOLL样受体 

分 类 号：R587.1[医药卫生—内分泌]