SphK1-S1P信号通路的激活参与糖尿病大鼠肾损伤的研究  

Activation of SphK1-S1P signaling pathway is involved in diabetic rat renal injury

作　　者：兰天[1] 常秀亭[2] 勾红菊[1] 吴腾[1] 王丽京[1] 黄河清[2] 

机构地区：[1]广东药学院血管生物学研究所,广州510006 [2]中山大学药学院,广州510006

出　　处：《重庆医学》2013年第22期2571-2573,共3页Chongqing medicine

基　　金：国家自然科学基金资助项目(81170676;81200308;31271455)

摘　　要：目的观察鞘氨醇激酶1-1-磷酸鞘氨醇(SphK1-S1P)信号通路在链脲佐菌素(STZ)诱导的糖尿病大鼠肾脏中的激活情况。方法观察STZ诱导的糖尿病大鼠肾脏中SphK1-S1P信号通路的激活情况。分别检测大鼠肾脏功能及病理指标。采用液质联用分析SphK1活性及S1P含量。并采用免疫组织化学、Real-time PCR和Western blot法检测了SphK1的表达。结果 STZ诱导的糖尿病大鼠血糖、肾重体质量比、24h尿蛋白显著升高,糖尿病大鼠肾脏系膜区肥大,细胞外基质扩展。同时,糖尿病大鼠肾脏中SphK1-S1P信号通路被激活,表现为SphK1表达和活性增加,以及S1P生成增加。结论糖尿病大鼠肾脏中存在SphK1-S1P信号通路的激活,可能参与了糖尿病大鼠肾损伤过程。Objective We aimed to investigate whether SphK1-S1P signaling pathway is activated in diabetic nephropathy.Methods SphK1 activity and S1P levels were measured by LC-MS/MS analysis.The expression of SphK1 were examined by immunohistochemistry,real-time PCR and Western blot.Results Fasting blood glucose,kidney/body weight ratio and 24-h albuminuria were significantly increased in diabetic mice.Furthermore,mesangial hypertrophy was found in diabetic kidney.Strikingly,the staining,activity and levels of mRNA and protein of SphK1,and S1P production in diabetic kidney were also markedly increased in diabetic mouse kidney.Conclusion These results demonstrate that the SphK1-S1P signaling pathway is activated in diabetic kidney,suggesting that SphK1-S1P signaling pathway is implicated in the pathogenesis of diabetic nephropathy.

关 键 词：SphK1-S1P信号通路 纤维连接蛋白 糖尿病肾病 STZ 

分 类 号：R587.1[医药卫生—内分泌]