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任凌燕,朱鸣,霍丽霞,王霄一.Kindlin-2介导足细胞损伤在局灶节段肾小球硬化症小鼠中的作用研究[J].浙江中西医结合杂志,2018,28(9):
Kindlin-2介导足细胞损伤在局灶节段肾小球硬化症小鼠中的作用研究
The role of Kindlin-2 in mediating podocyte injury in focal segmental glomerulosclerosis mice
投稿时间:2018-03-14  修订日期:2018-07-15
DOI:
中文关键词:  Kindlin-2  足细胞损伤  局灶节段肾小球硬化症
英文关键词:Kindlin-2  podocyte injury  focal segmental glomerulosclerosis
基金项目:浙江省医药卫生科技项目[2017KY639],湖州市科技计划项目[2016GY27]
作者单位E-mail
任凌燕 湖州市第一人民医院 742817307@qq.com 
朱鸣 湖州市第一人民医院  
霍丽霞 湖州市第一人民医院  
王霄一 湖州市第一人民医院 296246634@qq.com 
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中文摘要:
      目的:探讨Kindlin-2介导足细胞损伤在局灶节段肾小球硬化症小鼠中的作用研究。方法:8周龄雄性BALB/C小鼠分为正常对照组(n=18)、模型组(n=18)。模型组注射阿霉素造模,正常对照组给予等量的生理盐水,于第4、8、12周每组各处死6只小鼠,检测24h尿蛋白定量、ALB、TC,光镜观察肾脏组织病理学改变。WT1免疫组织化学技术检测足细胞数量。RT-qPCR技术检测肾脏组织Kindlin-2、nephrin及podocin mRNA水平。结果:与正常对照组比较,第4周开始模型组24h尿蛋白定量(5.66±1.06)mg/24h、(4.63±1.16)mg/24h、(4.78±0.87)mg/24h;TC(6.67±0.96) mmol/L、(4.68±0.70) mmol/L、(2.49±0.60)mmol/L均增加(P均<0.05), 而ALB(11.98±1.33)g/L、(12.78±1.47)g/L、(12.99±1.38)g/L下降(P均<0.05);模型组第4周可见部分肾小球出现局灶、节段硬化,伴有足细胞肿胀;第8周部分肾小球出现球性硬化,伴有明显的足细胞增生和肥大;第12周弥漫性肾小球出现球形硬化。模型组足细胞数量[(77.40±7.56)个/肾小球]、[(63.27±8.51)个/肾小球]、[(53.15±8.23)个/肾小球]随着时间的进展逐渐减少。模型组第4周开始Kindlin-2 mRNA水平(1.114±0.057)、(1.129±0.078)、(1.452±0.104)明显上调(均P<0.05),Podocin mRNA水平(1.793±0.080)、(1.636±0.059)、(1.454±0.067)明显下调(P均<0.05),第8周开始Nephrin mRNA(1.421±0.130)、(1.168±0.113)水平明显下调(均P<0.05)。Kindlin-2 mRNA水平与足细胞数量(r=-0.02, P <0.001) 、Nephrin mRNA水平(r=-0.8, P <0.01) 、Podocin mRNA水平(r=-0.9, P <0.01) 呈显著负相关。结论:Kindlin-2可能通过介导足细胞损伤参与了局灶节段肾小球硬化症小鼠的发病过程。
英文摘要:
      Objective To investigate The role of Kindlin-2 in mediating podocyte injury in focal segmental glomerulosclerosis mice.Methods Male BALB/C mice with 8 weeks of age were divided into two groups: normal control group and model group, each group had 18 mice. The model group were given adriamycin by tail intravenous injection, and the normal control group were given the same amount of normal saline. Six mice were sacrificed at 4th, 8th, 12th week.To compare the levels of 24 hour urinary protein, serum albumin, serum cholesterol at 4th,8th,12th week separately and to observe the pathology of kidney by light microscop. By immunohistochemistry method for detection of Wilms’ tumor(WT1) in the glomerulus and count the number of podocyte. Real-time quantitative PCR was used to detect Kindlin-2, Nephrin and Podocin mRNA. Results After being injected ADR for 4,8,12weeks, the level of 24 hour urinary protein(5.66±1.06)mg/24h、(4.63±1.16)mg/24h、(4.78±0.87)mg/24h,serum cholesterol(6.67±0.96) mmol/L、(4.68±0.70) mmol/L、(2.49±0.60)mmol/L went up significantly(P<0.05), while serum albumin(11.98±1.33)g/L、(12.78±1.47)g/L、(12.99±1.38)g/L decreased significantly(P<0.05). In the model group, some glomeruli showed focal and segmental sclerosis accompanied by podocyte swelling at 4th week. Part of the glomerular showed spherical sclerosis accompanied by significant podocyte proliferation and hypertrophy at 8th week. Diffuse glomerular showed spherical sclerosis at 12th week. The number of podocyte[(77.40±7.56)per glomeruli]、[(63.27±8.51)per glomeruli]、[(53.15±8.23)per glomeruli] gradually decreased over time in the model group .In the model group, the level of Kindlin-2 mRNA(1.114±0.057)、(1.129±0.078)、(1.452±0.104)was significantly up-regulated at 4th week(P<0.05) .The level of Podocin mRNA(1.793±0.080)、(1.636±0.059)、(1.454±0.067)was significantly down-regulated at 4th week(P<0.05).The level of Nephrin mRNA (1.421±0.130)、 (1.168±0.113) was significantly down-regulated at 8th week(P<0.05) .The expression of Kindlin-2 was negatively correlated with the number of podocyte(r=-0.02, P <0.001),and the expression of Nephrin(r=-0.8, P <0.01)and Podocin(r=-0.9, P <0.01). Conclusion Kindlin-2 may participate in the pathogenesis of focal segmental glomerulosclerosis in mice through mediating podocyte injury.
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