中文摘要：

目的探讨血凝素样氧化低密度脂蛋白受体1（LOX-1）在氧化低密度脂蛋白（OX—LDL．）诱导肾小管上皮细胞转分化中的作用及其可能机制．方法体外培养NRK-52E细胞，加入不同浓度（0、25、50、100mg／L）的OX—LDL刺激24h.LOX-1阻滞剂多聚肌苷酸（poly I，250mg／L）和爱兰苔胶（carrageenan，250mg／L）及抗氧化剂N-乙慌-L-半胱氨酸（NAC，5mmol／L）预处理后50mg／LOX—LDL共同孵育。用实时定量PCR测定LOX-1mRNA的表达水平，Western印迹测定IDX—1、E钙黏蛋白（Cadherin）及仪平滑肌肌动蛋白（SMA）蛋白表达；油红O检测细胞内脂质；激光共聚焦榆洲ROS。结果（1）α～100mg／L范围ox—LDL以浓度依赖方式增加LOX-1mRNA和蛋h的表达。随着LOX-1表达增加，细胞内脂质增多，活性氧产生增α—SMA表达增加，E—cadherin降低。（2）polyl或爱兰苔胶预处理组LOX-1mRNA和蛋白表达被显著抑制，同时细胞内脂质和ROS减少，α-SMA表达减少，E—cadherin增加，与对照组差异均有统计学意义（均P〈0．05）。（3）NAC预处理2h后，细胞内ROS减少，α-SMA减少，E-cadherin增加，LOX—1表达下调（均P〈0．05）。（4）α-SMA表达与ROS水平呈正相关（r=0．87，P〈0．05），E—cadherin表达与ROS水平呈负相关（r=-0．82，P〈0．05）。结论OX—LDL可能结合LOX-1促进ROS产生而诱导肾小管上皮细胞转分化。

英文摘要：

Objective To investigate the effec.t of leetin-like oxidized low-density lipoprotein receptor 1（ LOX-1 ） on tubular epithelial-myofibroblast transdifferentiation（TEMT） induced by nxidized-low density lipoprotein （ox-LDL） and to elucidate its possible mechanism. Methods NRK-52E cells were incubated with ox-LDL, （0, 25, 50 and 100 mg/L） lot 24 hours or pre-treated with the chemical blocker of LOX-1 receptor, polyI （250 mg/L）or carrageenan （250 mg/L ） or antioxidant- NAC,and then exposed to 50 mg/L ox-LDL. LOX-1 mRNA was examined by real-time PCR. LOX-1 and E-eadherin and α-SMA protein were assessed by Western blotting. Lipid deposit was examined by oil red O and ROS prodnetinn was evaluated by confncal laser scanning mieroseopy. Results （1）ox-LDL increased the expression of LOX-1 mRNA and protein in dnsc-dependent manner from 0 mg/L to 100 mg/L. Following the increase of LOX-1, lipid intake,ROS generation and α-SMA expression were all increased, but E-eadherin was decreased. （2）Pretreatment with Poly 1 or carrageenan significantly inhibited ox-LDL-induced LOX-1 expression （P〈0.05）, lipid intake （P〈0.05） and ROS generation （all P〈0.05）, which were associated with the deerease of α-SMA expression anti the inerease of E-cadherin expression. （3）Pre-treatment with NAC also inhibited ROS generation （P〈0.05）, the expression of α-SMA and LOX-1 （all P〈 0.05）, but inereased the E-eadherin expression （P〈0.05）. （4）α-SMA expression was positively correlated with ROS generation （r=0.87, P〈0.05）, and E-eadherin expression was negatively correlated with ROS generation （r =-0.82, P〈0.05）. Conclusion ox-LDL can induce tubular epithelial-myofibrofiblast transdiffe.rentiation through hinding to LOX-1 and promoting ROS genet;ation.