SOCS3在糖尿病小鼠肾小管间质病变中的作用

Role of SOCS3 in tubulointerstitial injury of mice with diabetes

目的探讨细胞因子信号传导抑制蛋白3(suppressors of cytokine sigmaling,SOCS3)在糖尿病小鼠肾损伤中的作用。方法雄性CD-1小鼠腹腔注射链脲佐菌素(streptozotocin,STZ)诱发糖尿病小鼠模型,成模后8周给予尾静脉快速注射p EFFLAG-I/m SOCS3质粒(1 mg/kg),每隔7天注射1次。成模后12周收集肾皮质,应用透射电镜观察肾小管上皮细胞形态学改变;分别应用RT-PCR和免疫组化法检测CK18和α-SMA mRNA和蛋白的表达;Western blot法检测SOCS3、p-STAT3、CK18和α-SMA的表达。结果与正常对照鼠相比,糖尿病小鼠肾组织中p-STAT3、SOCS3和α-SMA的表达增高,CK18表达降低。SOCS3质粒注射后能下调p-STAT3和α-SMA的表达水平同时上调CK18的表达。结论 SOCS3可能通过抑制信号转导和转录活化因子3(signal transducers and activators of transcription 3,STAT3)的磷酸化从而缓解糖尿病鼠肾小管上皮细胞转分化。

Purpose To investigate the role of SOCS3 on diabetic renal injury. Methods Male CD-1 mice were randomly divided into four groups： control group, diabetic group, empty plasmid vector transfection group and SOCS3 plasmid transfection group. The diabet- ic mice were induced by intraperitoneal injection of STZ at a dose of 150 mg/kg body weight. The mice of transfeetion group were re- ceived an injection of SOCS3 plasmid or empty vector at every 7 clays thereafter. Specimens were collected at 12 week after STZ injec- tion. The morphological changes of tubular epithelial cells were observed by transmission electron microscope. RT-PCR and imnmno- histochemistry were used to determine the mRNA and protein expression of CK18 and α-SMA. Western blotting analysis was used to determine the protein expression of SOCS3, p-STAT3, CK18 and α-SMA. Results SOCS3 overexpression in kidney down-regulated the levels of p-STAT3 and α-SMA but up-regulated the expression of CK18. Conclusion Overexpression of SOCS3 can ameliorate the tubular epithelial-mesenchymal transdifferentiation of diabetic mice via inhibiting the phosphorylation of STAT3.