SphK1-S1P信号通路的激活参与糖尿病大鼠肾损伤的研究

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、24 h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.Meth-ods SphK1 activity and S1P levels were measured by LC-MS/MS analysis.The expression of SphK1 were examined by immuno-histochemistry,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 stai-ning,activity and levels of mRNA and protein of SphK1,and S1P production in diabetic kidney were also markedly increased in dia-betic 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.