SOCS1在糖尿病小鼠肾小管间质病变中的作用

The Role of SOCS1 in Tubulointerstitium Injury of Mice with Diabetes

该文探讨了细胞因子信号传导抑制蛋白1(suppressors of cytokine sigmaling 1,SOCS1)在糖尿病小鼠肾小管间质病变中的作用。通过腹腔注射链脲佐菌素(streptozotocin,STZ)诱发糖尿病小鼠模型,于成模后8周给予尾静脉快速注射p EF-FLAG-I/m SOCS1质粒(1 mg/kg),每隔7 d注射一次。于成模后12周收集标本,检测各组动物的血糖、24 h尿蛋白;应用RT-PCR检测肾组织中SOCS1、角蛋白18(cytokeratin,CK18)和α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)m RNA的表达;应用免疫组化或Western blot检测SOCS1、CK18、α-SMA和纤维黏连蛋白(fibronectin,FN)的表达;酶联免疫吸附实验检测肾组织中白细胞介素-1β(interleutin-1β,IL-1β)和转化生长因子-β1(transforming growth factor-β1,TGF-β1)的表达;流式细胞术检测肾皮质中巨噬细胞标志蛋白CD68的表达。结果发现,与对照组相比,糖尿病小鼠肾组织中IL-1β、TGF-β1及FN的表达增强,巨噬细胞的数量增多;此外,肾小管上皮细胞自身标志蛋白CK18的表达减少而肌成纤维细胞标志蛋白α-SMA的表达增强。SOCS1质粒转染能降低24 h尿蛋白、抑制肾组织中CD68、IL-1β、TGF-β1和α-SMA的表达,同时部分恢复CK18的表达。结果表明,SOCS1可能通过抑制肾组织炎症反应和肾小管上皮细胞转分化从而缓解糖尿病小鼠肾小管间质病变。

The aim of this study is to investigate the role of SOCS1 on diabetic renal injury. The diabetic mice were induced by intraperitoneal injection of STZ at a dose of 150 mg/kg body weight. The mice of transfection group were received an injection of SOCS1 plasmid or empty vector every 7 days. At 12 weeks after STZ injection, specimens were collected to detect the blood glucose and 24 hours urine protein. RT-PCR analysis was used to detecte the expression of SOCS1, CK18 and α-SMA m RNA. Immunohistochemistry or Western blot analysis was used to determine the expression of SOCS1, CK18, α-SMA and FN. The expression of CD68 was detected by flow cytometry. The secretion level of IL-1β and TGF-β1 was detected by ELISA. The results suggested that overexpression of SOCS1 in kidney ameliorated excretion of urine protein and inhibited the expression of CD68, IL-1β, TGF-β1 and FN. In addition, SOCS1 overexpression increased the expression of CK18 and decreased the expression of α-SMA in tubular epithelial cells. All of the results indicated that overexpression of SOCS1 could reduce the inflammatory response and inhibit the tubular epithelial-mesenchymal transdifferentiation in renal tissue of diabetic mice and relieve renal tubular interstitial damage.