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目的:探讨糖尿病大鼠肾组织肿瘤坏死因子α(TNF-α)、核转录因子- κB (NF-κB)对肾组织细胞凋亡的诱导以及雷帕霉素干预的作用.方法:选择2型糖尿病大鼠(GK大鼠)20只,均分为糖尿病模型组(DM组),雷帕霉素治疗组(DMR组,建立糖尿病模型后给予雷帕霉素治疗);另选择10只Wistar雄性大鼠作为正常对照组.分别在4周、8周后检测各组肾组织细胞凋亡情况,NF- κB,TNF-α的表达水平以及血脂、血糖水平.结果:模型制作后4周、8周,与正常对照组和DMR组比较,DM组大鼠肾组织细胞凋亡数[RCA,4周(0.217±0.031)、(0.272±0.031)比(0.545±0.031)、8周(0.358±0.031)、(0.350±0.031)比(0.811±0.031)]均明显增多,NF-κBp65 [OD:4周(0.160±0.027)、(0.131±0.027)比(0.411±0.027)、8周(0.232±0.027)、(0.275±0.027)比(0.634±0.027)]、TNF-α [OD:4周(0.242±0.027)、 (0.275±0.027)比(0.617±0.027)、8周(0.385±0.027)、(0.342±0.027)比(0.912±0.027)]表达均明显升高(P均＜0.01).相关分析显示,肾组织NF-κBp65与TNF -α,RCA与TNF-α,NF -κBp65均呈正相关关系(r=0.956,0.953,0.886,P均＜0.01).结论:糖尿病病大鼠的肾细胞凋亡显著增加,雷帕霉素干预组肾细胞凋亡显著减少,NF- κB、TNF-α表达显著增加,其保护作用可能是NF- κB、TNF-α阻滞细胞的凋亡.“,”Objective:To investigate the apoptosis of renal cells induced by tumor necrosis factor alpha (TNF- a) and nuclear factor-κB (NF-κB) in diabetic rats and intervention of rapamycin.Methods:A total of 20 rats (GotoKakizaki rats) with type 2 diabetes mellitus (T2DM) were randomly and equally divided into DM model group (DM group) and rapamycin treatment group (DMR group,received rapamycin treatment after DM model was established) ; another 10 Wistar male rats were regard as normal control group.Apoptosis of renal cells,expression levels of TNF - α and NF- κB and levels of blood lipids,blood glucose were measured in all groups after four weeks and eight weeks.Results:Four and eight weeks after model was established,compared with normal control group and DMR group,there were significant increase in renal cells apoptosis [-RCA,four weeks:(0.217± 0.031),(0.272 ±0.031) vs.(0.545 ± 0.031),eight weeks:(0.358 ± 0.031),(0.350 ± 0.031) vs.(0.811 ± 0.031)] and expressions of NF-κB p65 [OD:four weeks:(0.160± 0.027),(0.131 ±0.027) vs.(0.411±0.027),eight weeks:(0.232± 0.027),(0.275 ± 0.027) vs.(0.634 ± 0.027)] and TNF- α [OD:four weeks:(0.242 ± 0.027),(0.275 ± 0.027)vs.(0.617 ± 0.027),eight weeks:(0.385 ± 0.027),(0.342 ± 0.027) vs.(0.912 ± 0.027)] in DM group (P＜0.01all).Correlation analysis indicated that there were positive correlations between renal NF - κB p65 and TNF - α,among RCA and TN F- α,NF- κB p65 ( r =0.956,0.953,0.886,P＜0.01 all).Conclusion:Renal cells apoptosis significant increase in rats with T2DM,but renal cells apoptosis significant decrease in DMR group,protection mechanism of rapamycin may be NF- κB、TNF- α inhibiting renal cells apoptosis.