糖尿病大鼠肾小球IL-18、ICAM-1和TNF-α表达的实验研究

目的探讨炎症细胞因子与糖尿病肾病（DN）发生、发展的关系。方法雄性SD大鼠32只分为糖尿病（DM）组20只和正常对照（NC）组12只。4、8周末检测血糖（BG）、尿素氮（BUN）、肌酐（SCr）及24小时尿蛋白（UPro/24h）。处死动物后计算肾重指数（KI）；镜下观察肾脏病理改变；检测肾小球白细胞介素18（IL-18）、细胞间黏附分子1（ICAM-1）、肿瘤坏死因子α（TNF-α）的表达。结果4、8周DM组分别与同期NC组相比：BG、KI、UPro/24h、SCr显著增高；肾小球体积增大、系膜细胞增生、毛细血管基底膜增厚、足突融合；IL-18、ICAM-1、TNF-α表达显著增高。8周DM组与4周DM组相比：KI、BUN、SCr、UPro/24h增高，肾脏病理改变加重，IL-18、ICAM-1、TNF-α在肾小球的表达增高。IL-18、ICAM-1、TNF-α三者表达之间呈正相关，与BUN、SCr、UPro/24h亦呈正相关（P均〈0.05）。结论糖尿病大鼠肾小球IL-18、ICAM-1、TNF-α的表达与DN的发生、发展密切相关。

The study on protein expressions of IL-18, ICAM-1 and TNF-α in glomeruli of diabetic rat

Objective To study the effect of inflammatory cytokines on diabetic nephropathy. Methods Blood glucose（BG）, blood urea nitrogen（BUN）, serum creatinine（Scr） and 24 hour urinary protein（24h UPro） were detected at the end of 4 weeks and 8 weeks study in male SD rats. The rats were divided into diabetes （DM） group and normal control （NC） group. Kidney weight/body weight ratio （KI） of rats were measured and calculated. Kidney pathological changes were observed by light microscope and electron microscope. Expressions of interleukin-18 （IL-18）, intercellular adhesion molecule-1 （ICAM-1） and tumor necrosis factor-alpha （TNF-α） in glomeruli were detected by immunohistochemical staining. Results Compared with homochronous NC group,BG,KI,24hUPro,Scr and expressions of IL-18, ICAM- 1,TNF-α were significantly higher in DM group （P〈0.05）, with larger volume of renal glomeruli, expansed mesangial cells, thickened glomerular basement membrance and mixed foot process. Compared with DM group at 4 weeks study,KI,BUN,Scr,24hUPro and expressions of IL-18, ICAM-1 ,TNF-α were higher in DM group at 8 weeks study（P〈0.05）, with more aggravated kidney pathological changes. The expressions of IL-18, ICAM-1, TNF-α were positively correlated with BUN, Scr, 24UPro, and the three inflammatory cytokines were related with each other. Conclusions Expressions of IL-18,ICAM-1 ,TNF-α in glomeruli are related with the progression of diabetic nephropathy, and the role of them in development of diabetic nephropathy is to be discussed further.