GSK-3β抑制剂对糖尿病肾病大鼠肾组织病理、NF-κB及TGF-β1的影响  

Effects of GSK-3βinhibitor on renal histopathology,NF-κB and TGF-β1 in diabetic nephropathy rats

作　　者：王雪梅[1] 陈海青 WANG Xuemei;CHEN Haiqing(Department of Quality Management Control,No.981 Hospital of the PLA,Chengde,Hebei 067000,China)

机构地区：[1]中国人民解放军联勤保障部队第九八一医院质量管理控制科,河北承德067000

出　　处：《检验医学与临床》2020年第23期3448-3452,共5页Laboratory Medicine and Clinic

摘　　要：目的探讨糖原合成酶激酶-3β(GSK-3β)抑制剂对糖尿病肾病(DN)大鼠肾组织病理、核因子-κB(NF-κB)及转化生长因子-β1(TGF-β1)的影响。方法将36只SD大鼠分为Tz组(DN模型)、Ty组(GSK-3β抑制剂干预)和Wt组(正常大鼠)各12只,观察比较3组大鼠24 h尿蛋白水平。采用苏木精-伊红(HE)染色观察肾组织结构改变情况,实时荧光定量PCR(RT-qPCR)检测NF-κB mRNA表达水平,免疫组织化学(免疫组化)检测TGF-β1阳性表达情况,Western blot法检测NF-κB、TGF-β1蛋白的表达情况。结果Tz组及Ty组大鼠24 h尿蛋白水平均高于Wt组,Ty组大鼠24 h尿蛋白水平低于Tz组,差异均有统计学意义(P<0.05)。Wt组大鼠肾组织内细胞结构、形态较完整,未观察到增生、肥大的细胞;Tz组大鼠肾小球、系膜基质生长异常,毛细血管管腔、肾小管管腔凹陷、阻塞,伴有间质水肿;Ty组大鼠肾小球和肾小管病变程度较Tz组有明显好转。Tz组、Ty组NF-κB、TGF-β1 mRNA水平高于Wt组,Ty组NF-κB、TGF-β1 mRNA水平低于Tz组,差异均有统计学意义(P<0.05)。免疫组化检测结果显示,Tz组TGF-β1阳性表达最高,Wt组TGF-β1阳性表达最低,Ty组TGF-β1阳性表达较Tz组明显降低,但高于Wt组,差异均有统计学意义(P<0.05)。Tz组及Ty组NF-κB、TGF-β1蛋白表达水平高于Wt组,Ty组NF-κB、TGF-β1蛋白表达水平低于Tz组,差异均有统计学意义(P<0.05)。结论GSK-3β抑制剂能减缓糖尿病肾病大鼠肾损伤程度,降低肾组织中NF-κB和TGF-β1的表达。Objective To investigate the effects of glycogen synthase kinase-3 beta(GSK-3β)inhibitor on renal histopathology,nuclear factor Kappa B(NF-κB)and transforming growth factor-β1(TGF-β1)in diabetic nephropathy rats.Methods Thirty-six Sprague-Dawley rats were randomly divided into Tz group(diabetic nephropathy model),Ty group(GSK-3βinhibitor intervention),Wt group(normal rats).The 24 h urinary protein levels of the 3 groups were observed and compared.The structural changes of renal tissues were observed by hematoxylin-eosin(HE)staining.The mRNA expression level of NF-κB was detected by RTqPCR,the positive expression of TGF-β1 was detected by immunohistochemistry,and the protein expression level of NF-κB and TGF-β1 were detected by Western blot.Results The 24 h urinary protein level of rats in Tz group and Ty group was significantly higher than that of Wt group,and the 24 h urinary protein level of Ty group was lower than that of Tz group,with statistically significant differences(P<0.05).The cell structure and morphology of the kidney tissue of the Wt group were relatively intact,and no hyperplastic or hypertrophic cells were observed.In the Tz group,the growth of glomerular and mesangial matrix was abnormal,and the capillary lumen and renal tubule were depressed and obstructed,accompanied by edema interstitium.The degree of glomerular and tubular lesions in the Ty group was significantly better than that in the Tz group.Compared with the Wt group,the levels of NF-κB and TGF-β1 in the Tz group and Ty group were significantly increased,and the expression of NF-κB and TGF-β1 in the Ty group was lower than that in the Tz group,with statistically significant differences(P<0.05).Immunohistochemical test results showed that the positive expression of TGF-β1 in Tz group was the highest,the positive expression of TGF-β1 in Wt group was the lowest,and the positive expression of TGF-β1 in Ty group was significantly lower than that in Tz group,but higher than that in Wt group,and the differences were statistical

关 键 词：糖尿病肾病 糖原合成酶激酶-3β抑制剂 核因子-ΚB 转化生长因子-β1 

分 类 号：R692.9[医药卫生—泌尿科学]