2型糖尿病患者早期肾损害外周血单个核细胞白细胞介素-18的表达

Interleukin-18 expression in PBMC of type 2 diabetes mellitus patients with early kidney damage

目的：考察单个核细胞白细胞介素-18的表达与糖尿病患者早期肾损害之间的相关性。方法分别选取绍兴市人民医院2010年1月至2012年12月2型糖尿病（ T2DM）患者480例，按照尿白蛋白排出率分为糖尿病组、微量蛋白尿组和蛋白尿组，另选160例正常体检者作为对照组，检测其糖化血红蛋白、血胆固醇、血甘油三酯、血肌酐、尿素氮、餐后2h血糖和尿微量蛋白；分离获取单个核细胞体外培养12 h、24 h后，检测IL-18含量；进行IL-18基因启动子-137G／C、-607C／A位点基因多态性进行检测。结果身体质量指数（ BMI）、餐后2 h血糖、胆固醇、糖化血糖蛋白、尿素氮和血肌酐指标，正常组显著低于糖尿病组、微量蛋白尿组和蛋白尿组（ P＜0.01）；餐后2 h血糖、胆固醇、糖化血糖蛋白、尿素氮和血肌酐指标，微量蛋白尿组和蛋白尿组均高于糖尿病组（ P＜0.05）；尿蛋白量、12 h IL-18和24 h IL-18指标，糖尿病组、微量蛋白尿组和蛋白尿组均显著高于正常组（ P＜0.01），微量蛋白尿组和蛋白尿组显著高于糖尿病组（P＜0.01）；尿蛋白量与12 h IL-18、24 h IL-18呈正相关（r＝0.454，P＜0.01；r＝0.479，P＜0.01）；IL-18基因-607C／A多态性在各组别差异无统计学意义（P＞0.05）；在-137G／C基因，蛋白尿组与糖尿病组比较，各基因型频率分布差异有统计学意义（χ2＝5.45，P＜0.05），各等位基因频率分布差异有统计学意义（χ2＝5.76，P＜0.05）。结论 IL-18可作为糖尿病肾早期损伤的检测指标，－137G／C基因多态性可能通过促进IL-18的高度表达而增加糖尿病肾病发病风险。

Objective To investigate the correlation between the expression of mononuclear cells Inter-leukin-18（IL-18）and early renal damage in diabetic patients.Methods 480 cases with type 2 diabetes mellitus （T2DM）in our hospital from Jan.2010 to Dec.2012 were selected.According to urine albumin excretion rate, They were randomly divided into diabetic group, micro proteinuria group, and proteinuria group.160 cases of normal people were selected as the control group.Glycosylated hemoglobin, serum cholesterol, serum triglycer-ides, serum creatinine, blood urea nitrogen.2 h postprandial blood glucose and urine protein were detected.Af-ter mononuclear cells being isolated and cultured for 12 h and 24 h, IL-18 was detected.-137G/C and-607C/A gene polymorphism were detected.Results Normal group were significantly lower than diabetes group, micro proteinuria group, and proteinuria group（P〈0.01）in BMI, 2 h postprandial blood sugar, cholesterol, glycosy-lated protein, urea nitrogen and serum creatinine index.Micro proteinuria group and proteinuria group were high-er than diabetic group in 2 h blood sugar, cholesterol, glycosylated protein, urea nitrogen and serum creatinine index（P〈0.05）.Diabetes group, micro proteinuria group, and proteinuria group were significantly higher than normal group in urine protein, 12 h IL 18 and 24 h IL-18（P〈0.01）.Micro albuminuria and proteinuria group was significantly higher than diabetic group in urine protein, 12 h IL 18 and 24 h IL-18（P〈0.01）.There were positive correlation between urine protein and 12 h, 24 h IL-18（r=0.454, P〈0.01; r=0.479, P〈0.01）.nbsp;There was statistical difference between albuminuria group and diabetes group in -137G/C genotype frequency （χ2 =5.45, P〈0.05） and there was statistical differencebetween the allele frequency distribution（χ2 =5.76, P〈0.05） .Conclusions IL-18 can be used as an indicator for detecting early renal damage.Gene -137G/C polymorphism may increase the risk of diabetic nephropathy by upregulating the expression of IL-18.