血管内皮细胞MEKK3在小鼠肾脏缺血再灌注损伤中的作用

Role of vascular endothelial cell MEKK3 in renal ischemia-reperfusion injury of mice

目的探讨血管内皮细胞MEKK3对肾缺血再灌注损伤的保护作用,进一步明确MEKK3在肾缺血再灌注损伤中的作用机制。方法Cdh5-CreERT2 Mekk3 fl/-小鼠通过喂食他莫昔芬后特异性敲除血管内皮细胞中的MEKK3。基因敲除小鼠及对照组构建缺血再灌注损伤模型48h后检测小鼠血肌酐、尿白蛋白和肾脏病理学改变,评价MEKK3对小鼠肾缺血再灌注损伤的保护作用。结果MEKK3在血管内皮细胞的表达能改善再灌注损伤后小鼠肾功能,减轻肾组织损伤和炎症反应,敲除血管内皮细胞的MEKK3能加重缺血再灌注损伤,凋亡及炎症细胞浸润明显,磷酸化的Smad2表达升高,血肌酐和尿蛋白水平明显升高。结论血管内皮细胞中MEKK3的表达对肾缺血再灌注损伤产生保护作用,其机制可能和抑制Smad2的磷酸化有关。

Objective To investigate the protective effect of MEKK3 on renal ischemia-reperfusion injury and its effect on apoptosis, and further clarify the mechanism of MEKK3 in renal ischemia-reperfusion injury. Methods Cdh5-CreERT2 Mekk3 fl/- mice was fed with tamoxifen to specifically knockout MEKK3 in vascular endothelial cells. The protective effects of MEKK3 on renal ischemia-reperfusion injury in mice were evaluated by measuring serum creatinine, urine protein and pathological scores 48 hours after ischemia-reperfusion injury in two groups of mice. Results The expression of MEKK3 in vascular endothelial cells could improve the renal function of mice after reperfusion injury, and alleviate renal tissue damage and inflammation. MEKK3 knocking out vascular endothelial cells could aggravate ischemia-reperfusion injury, and serum creatinine and urinary protein levels were significantly increased. Apoptotic and inflammatory cell infiltration was evident. Conclusions The expression of MEKK3 in vascular endothelial cells has protective effects on renal ischemia-reperfusion injury, and this may be related to the phosphorylation of Smad2.