TNF-α、NF-κB诱导糖尿病大鼠肾脏细胞凋亡及雷帕霉素干预影响(英文)  

Apoptosis of renal cells induced by TNF-α and NF-κB in diabetic rats and intervention of rapamycin

作　　者：徐锦春[1] 陈思娇[1] 熊盈[1] 陈婕[1] 宋今丹[2] 

机构地区：[1]中国医科大学附属第一医院老年病教研室,辽宁沈阳110001 [2]中国医科大学医学分子生物学研究所,卫生部细胞生物学重点实验室

出　　处：《心血管康复医学杂志》2012年第2期117-122,F0002,共7页Chinese Journal of Cardiovascular Rehabilitation Medicine

基　　金：Scientific and technological project in Liaoning Province(2011225052-2011020216-428)~~

摘　　要：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-α） and nuclear factor-κB（NF-κB） in diabetic rats and intervention of rapamycin.Methods：A total of 20 rats（Goto-Kakizaki 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 and expressions of NF-κB p65 and TNF-α in DM group（P0.01 all）.Correlation analysis indicated that there were positive correlations between renal NF-κB p65 and TNF-α,among RCA and TNF-α,NF-κB p65（r=0.956,0.953,0.886,P0.01 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.

关 键 词：糖尿病 2型 细胞凋亡 西罗莫司 大鼠 

分 类 号：R587.109[医药卫生—内分泌]