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.%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 hema-toxylin-eosin (HE) and periodic acid-Schiff reaction (PAS) staining. The protein levels of LOX-1 and transforming growthrnfactor 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-1 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.
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