阿巴西普对2型糖尿病大鼠肾脏的保护作用

Protective effect of abatacept in on kidney function in rats with type 2 diabetes melitus

目的探讨阿巴西普对2型糖尿病(T2DM)大鼠肾脏的保护作用。方法将45只雄性SD大鼠分为对照组、阿巴西普组和无干预组,每组15只。阿巴西普组和无干预组经高糖、高脂喂养联合小剂量链脲佐菌素构建T2DM大鼠模型,阿巴西普组大鼠尾静脉注射阿巴西普0.5mg/kg,1次/周,共干预8~10周,直至无干预组发展成糖尿病肾病(DN),对照组不采取任何干预措施。最后以彩色多普勒超声检测肾动脉主干血流参数,超声弹性成像检测肾实质弹性,收集血液检测生化指标,肾组织作病理检查,透射电镜观察足细胞超微结构改变,Western blot检测肾组织B7-1的表达情况。结果各组间的肾动脉主干血流收缩期峰值流速(PSV)、舒张末期流速(EDV)和平均流速(MV)均有统计学差异(均P<0.05),且无干预组<阿巴西普组<对照组;各组间的肾动脉主干血流收缩期加速度(SAC)、搏动指数(PI)和阻力指数(RI)均有统计学差异(均P<0.05),且无干预组>阿巴西普组>对照组。各组间的肾弹性评分有统计学差异(P<0.05),且无干预组>阿巴西普组>对照组。无干预组和阿巴西普组的空腹血糖(FBG)、内生肌酐清除率(Ccr)、24h尿白蛋白排泄率(UAER)均高于对照组(均P<0.05);阿巴西普组的Ccr、UAER均低于无干预组(P<0.05)。肾组织HE染色和透射电镜观察足细胞超微结构显示无干预组和阿巴西普组都存在肾实质结构改变,无干预组较阿巴西普组严重。各组间肾组织B7-1表达水平有统计学差异,对照组<阿巴西普组<无干预组。结论阿巴西普能够明显抑制T2DM大鼠肾动脉主干血流阻力增加和流速降低、肾实质硬度增加、肾小球和足细胞病理改变,对T2DM大鼠肾脏具有保护作用。

Objective To investigate male the effect Dawley of abatacept（SD）on were kidney function in rats with type 2 diabetes melittus（T2DM）.nonMethods Forty five Sprague each rats divided was into control group,highabatacept group fat and intervention group small with 15 rats in group.Type 2 diabetic model established and with sugar group.main and The artery the high-feeding combined group with dose 0.5mg of kgthe streptozotocin 1（STZ）in 8-rats of abatacept group non-intervention rats in abatacept were given w-1 abatacept for 10 weeks.The blood flow parameters with of renal determined blood with color Doppler ultrasound;elasticity histology of of renal renal the parenchymal parenchymal expression was was B7-determined examined ultrasonic elastography;biochemical indexes were measured,electron the with HE was staining;detected（EDV）the ultrastructure of podocytes Results was There three examined were with microscopy and of 1 end in renal tissues with Western blot.significant differences in peak systolic ranked velocity（PSV）,diastolic velocity and mean velocity（MV）among groups,and these indicators were as nonintervention（SAC）,groupabatacept groupcontrol group index（P〈0.05）.There were significant ranked differences in systolic acceleration pulsatility（PI）and resistance index（RI）among three groups,which as nonintervention groupabatacept groupcontrol group（P〈0.05）.There were significant differences in the stiffness of kidney control nonamong group,three groups,which ranked as nonintervention creatinine groupabatacept groupcontrol group（P〈0.05）.Compared to the excretion fasting blood glucose（FBG）,clearance increased group rate（Ccr）and urine albumin rate（UAER）in the intervention and abatacept groups were significantly（P〈0.05）;while Ccr and UAER in the abatacept group were significantly lower than those in the nonintervention（P〈0.05）.HE staining and transmission electron microscopeobservation showed that there were significant changes in the renal parenchyma of rats in the nonintervention group and the abatacept group,and the changes of kidney in the nointervention group were worse than those in the abatacept group.There were significant differences in the B7-1 expression in renal tissues among these three groups,which ranked as control groupabatacept groupnonintervention group（P〈0.05）.Conclusion Abatacept can significantly inhibit the damage of renal function,the increase of resistance and decrease of velocity of renal blood flow,increase of renal parenchyma stiffness,thickening of glomerular basement membrane,reduction of podocytes in diabetic rats,indicating that abatacept can attenuate the renal injury and protect the renal function in type 2 diabetic rats to some extent.