β-连环蛋白在糖尿病大鼠肾小管中的表达及意义

Expression of β-catenin and its significance in renal tubules of diabetic rats

目的观察β-连环蛋白(β-catenin)在糖尿病大鼠肾小管中的表达,初步探讨其与糖尿病肾病(DN)发生发展的关系。方法雄性SD大鼠72只,随机分为正常对照组(C组)和糖尿病组(D组),分别观察2、4、8、12、16和24周。生化方法检测血糖、血肌酐和尿蛋白水平。PAS染色观察肾小管-间质损伤程度。免疫组织化学法检测β-catenin、α-平滑肌肌动蛋白(α-SMA)和纤连蛋白(FN)表达,RT-PCR法检测β-catenin mRNA水平。结果 D组各时点血糖、血肌酐和尿蛋白明显高于C组。与C组相比,D组肾皮质β-catenin蛋白和mRNA表达量无明显变化,胞核内蛋白表达明显增强(P<0.01)。C组α-SMA仅在血管壁表达,D组从2周开始,随病程进展间质细胞胞浆阳性染色逐渐增多,第16周和24周可见少数肾小管表达。FN在D组大鼠肾小管-间质表达从2周开始逐渐增多,与C组比较差异有显著性(P<0.05)。结论 DM大鼠β-catenin蛋白肾小管上皮细胞胞核内表达增强,肾间质α-SMA、FN蛋白表达增多,提示β-catenin可能由于降解减少后胞浆内增多而转移入核,参与了肾小管上皮细胞的转分化过程,促进了DN的发生发展。

【Objective】 To observe the expression of β-catenin in renal tissues of diabetic rats,and explore its effect in the development of diabetic nephrophy.【Methods】 Eighty-four adult SD male rats were randomly divided into control group and DM group.Both groups were observed and compared at 2,4,8,12,16 and 24 W.Periodic acid-silver（PAS） staining was used to observe the tubule-interstitial injury.Blood glucose,24h urine protein,serum creatinine（Scr） of rats was measured.The protein or mRNA expressions of β-catenin,α-SMA and FN in renal cortex were detected by immunohistochemical staining and reverse transcriptase,PCR（RT-PCR） respectively.【Results】 The levels of blood glucose,24 h urine protein、 Scr were increased remarkably in diabetic rats as compared with those in control groups（P 0.05,P 0.01）.There were no difference in protein and mRNA of β-catenin in DM and control rats,but its expression was remarkably up-regulated in nucleus.In DM rats,interstitial and tubular staining of α-SMA were seen at the 2nd and 16th week respectively.The FN and α-SMA protein were significant increased in DM rats as compared with that of the controls.【Conclusion】 These date suggest that β-catenin might be probably involved in epithelial-mesenchymal transition（EMT） of tubular epithelial cell and promoted the development of diabetic nephropathy.