LOX-1在2型糖尿病大鼠肾小管间质中的表达及其意义

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

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-β1mRNA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-β1mRNA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 intraperitflneal 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 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-1 mRNA with UAER, TNF-α and TGF-β1 were observed （r =0. 509, 0. 649 and 0. 800, respectively, P 〈0.05）. CON- CLUSION： 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.