Ox-LDL受体CD36与糖尿病大鼠肾小管损伤的关系

The correlation between oxidized low density lipoprotein receptor CD36 and renal tubular injury in diabetic rats

目的：本研究通过观察糖尿病大鼠肾组织氧化型低密度脂蛋白（ Ox-LDL）受体CD36的表达及Ox-LDL处理大鼠肾小管NRK-52E细胞后的CD36表达变化,探讨糖尿病肾病进展过程中CD36与肾小管损伤、肾纤维化的关系。方法高糖高脂联合小剂量链脲佐菌素诱导建立糖尿病合并高脂血症大鼠模型,切取肾脏用于CD36表达的免疫组化分析,同时对肾组织硬化及纤维化指标进行半定量评定。50 mg/L OxLDL分别处理NRK-52E细胞5、10、24和48 h或100和150 mg/L的OxLDL处理NRK-52E细胞2、3 d后后收集细胞,Western印迹法检测CD36蛋白水平。结果与对照组比较,糖尿病组大鼠肾组织中CD36表达明显升高,CD36主要表达在肾小管。糖尿病组肾小管损伤分数（STI）明显高于对照组（5.54±1.5 对0.65±0.15,P＆lt;0.05）。 OxLDL呈剂量时间依赖性地刺激肾小管NRK-52E细胞CD36的表达。结论 CD36在糖尿病大鼠肾小管的表达明显增高,并与STI一致,OxLDL增加肾小管NRK-52E细胞CD36的表达,提示Ox-LDL受体CD36表达可能与实验性糖尿病大鼠的肾小管损伤存在关联。

Objective To observe the expressions of oxidized low density lipoprotein （ OxLDL ） receptor CD36 in kidney tissue of diabetic rats and in tubular cells incubated with OxLDL, and to explore the association of CD36 with the tubular injury and renal fibrosis in the process of diabetic nephropathy. Methods Diabetic rat model with hyperlipidemia was established by feeding with high sugar and fat diet and injection of low dose streptozotocin intraperitoneally. The expression of CD36 in kidney tissues was analyzed immunohistochemically. Meanwhile, the tubular sclerosis and fibrosis injury index were estimated and calculated. NRK-52E cells were stimulated with 50 mg/L OxLDL for 5, 10, 24, and 48 h, or 100 and 150 mg/L OxLDLs for 2 and 3 days. The protein expression of CD36 was detected by Western blot. Results The expression of CD36 in the renal tubulointerstitium of diabetic rats was increased comparing to that in control rats, and was localized mainly at tubular region. The renal tubular damage index（STI）ofdiabetesgroupwashigherthanthatincontrolgroup（5.54±1.5vs0.65±0.15,P＆lt;0.05）. OxLDL stimulated CD36 expression in NRK-52E cells in a dose-and time-dependent manner. Conclusion The expression of CD36 was increased in renal tubular of diabetic rats, in consistent with STI. OxLDL increased CD36 expression in NRK-52E cells. These results suggest that the expression of CD36 is associated with renal tubular damages in experimental rat diabetes.