LOX-1在2型糖尿病大鼠肾小管间质中的表达及其意义

 目的：探讨血凝素样氧化低密度脂蛋白受体1（LOX-1）在糖尿病肾病（DN）中的作用及其机制。方法：SD大鼠随机分为正常对照组和糖尿病模型组。以高脂高糖饮食加低剂量注射链脲佐菌素复制2型糖尿病大鼠模型。动态观察：生化指标和24 h尿白蛋白排泄率（UAER）;苏木素伊红（HE）和过碘酸-雪夫反应（PAS）染色观察肾脏病理,免疫组化检测LOX-1和转化生长因子β1（TGF-β1）蛋白表达,荧光定量聚合酶链反应检测LOX-1和TGF-β1 mRNA表达,ELISA检测血清单核细胞趋化因子-1（MCP-1）、细胞间黏附分子（ICAM）和肿瘤坏死因子α（TNF-α）的浓度。结果：随着造模时间的延长,血清中总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）含量和UAER逐渐升高,高密度脂蛋白（HDL）在成模时升高,但随着病变进展含量减少;LOX-1和TGF-β1在肾小管中蛋白表达增加;与正常组比较,模型各组LOX-1和TGF-β1蛋白和mRNA表达逐渐增加;与正常组比较,模型各组血清MCP-1、ICAM和TNF-α水平均增高;LOX-1 mRNA表达与UAER、TNF-α和TGF-β1 mRNA表达量之间呈正相关（r值分别为0.509、0.649和0.800）（P<0.05）。结论：LOX-1在2型糖尿病肾小管中表达增加,使肾小管损伤,其作用可能通过炎症因子释放和炎症细胞浸润而实现,提示其在DN发生和发展过程中起重要作用。

Expression of LOX-1 in type 2 diabetic rat tubular interstitial tissues

AIM： To explore the effect of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) on type 2 diabetic nephropathy in rats. METHODS：The Sprague-Dawley (SD) rats were randomly divided into control group and model group. The animal model was established by intraperitoneal injection of low-dose streptozotocin (STZ, 30 mg/kg) plus feeding with high-fat/high-glucose diets for one month. Biochemical parameters and 24 h urine album excretion rate (UAER) were monitored. The morphological changes of the renal tissue were examined under microscope with hematoxylin-eosin (HE) and periodic acid-Schiff reaction (PAS) staining. The protein levels of LOX-1 and transforming growth factor β1 (TGF-β1) in the renal tissues were determined by the method of immunohistochemistry. The mRNA expression of LOX-1 and TGF-β1 was detected by real-time polymerase chain reaction. The serum levels of monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule (ICAM) and tumor necrosis factor α(TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The correlation between LOX-1 and UAER, inflammatory factors and TGF-β1 was analyzed. RESULTS：Compared with normal group, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and UAER in model groups markedly increased, high-density lipoprotein (HDL) only increased at 0 week, then decreased at 4 and 8 weeks. The expression of LOX-1 and TGF-β1 at mRNA and protein levels was increased, as well as the concentration of serum inflammatory factors such as MCP-1, ICAM and TNF-α. The obvious relations between LOX-l mRNA with UAER, TNF-α and TGF-β1 were observed (r=0.509, 0.649 and 0.800, respectively, P<0.05). CONCLUSION：LOX-1 is significantly increased in type 2 diabetic rat tubular interstitial tissues and aggravates the dysfunction of renal tubules by releasing inflammatory factors and promoting inflammatory cell infiltration.