左卡尼汀对糖尿病肾病大鼠的肾脏保护机制研究

Renoprotective effect of L-carnitine on streptozotocin-induced diabetic nephropathy in rats

目的:探讨左卡尼汀(L-carnitine,LC)对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病肾病(diabetic nephropathy,DN)大鼠肾脏保护的分子机制。方法:对雄性Sprague-Dawley大鼠腹腔注射STZ(65 mg/kg)建立糖尿病模型,造模成功大鼠给予LC(50 mg·kg^(-1)·d^(-1)或200 mg·kg^(-1)·d^(-1))12周治疗,检测各组大鼠的肾功能、24 h尿蛋白排泄率和肾小球硬化程度;免疫组化和Western blot法分别检测炎性因子、致纤因子、核因子κB和细胞凋亡调控基因的表达。结果:LC治疗可明显减轻糖尿病大鼠肾小球硬化,保持足细胞数量,这些改变伴随着尿蛋白排泄率的减少和肾功能的改善。在分子水平上,LC可下调炎性介质和致纤因子的表达,调节细胞凋亡调控基因的表达,此作用可能与干预核因子κB信号通路有关。结论:LC对STZ诱导的DN大鼠具有抗炎、抗肾小球硬化的肾脏保护作用。

AIM:To investigate whether L-carnitine(LC)treatment confers renoprotection in a rat model of streptozotocin(STZ)-induced diabetic nephropathy(DN).METHODS:Diabetic animal model was established by intraperitoneal injection of STZ(65 mg/kg)in Sprague-Dawley rats.Diabetic rats were treated with LC(50 mg·kg-1·d-1 or 200 mg·kg-1·d-1 intravenously)daily for 12 weeks.The effects of LC on STZ-induced DN were evaluated by assessing renal function,urinary protein excretion,histopathological changes,macrophage infiltration,the expression of proinflammatory and prosclerotic cytokines,and the expression of nuclear factor-κB(NF-κB)and apoptosis-related gene.RESULTS:LC administration significantly decreased glomerulosclerosis,preserved the number of podocytes,and reduced macrophage infiltration.These changes were accompanied by improvements in urinary protein excretion and renal dysfunction.LC treatment suppressed the expression of proinflammatory and prosclerotic cytokines,and these changes were paralleled by significant attenuation of NF-κB and apoptosis-related gene expression.CONCLUSION:LC has a renoprotective effect against STZ-induced DN in rats.