肾病综合征氧化低密度脂蛋白脂质肾损伤的实验研究

目的 通过观察氧化低密度脂蛋白（oxidized low-density lipoprotein,ox-LDL）对系膜细胞（Mesangial Cells,MCs）分泌炎症介质功能的影响及MAPK信号通路和核因子-κB（nuclear factor kappa B,NF-κB）活性的改变,进一步阐明脂质在肾损伤中的作用机制.方法 利用ox-LDL诱导大鼠系膜细胞增殖,分别采用ELISA、real-time PCR、western blot技术检测MCs炎症介质、MAPK通路相关蛋白（p38、JNK、ERK）及NF-κB的表达水平.结果 利用ox-LDL诱导大鼠系膜细胞增殖并加入CXCR6受体后,其表面炎症因子CXCL16、CD36、ADAM10、ADAM17、干扰素（IFN）、白细胞介素（IL6）、肿瘤坏死因子（TNF-α）]的表达水平以及MAPK信号通路（p38、JNK、ERK）、NF-κB的磷酸化水平显著升高（P〈0.01）.结论 ox-LDL可促使系膜细胞释放CXCL16、CD36、ADAM10、ADAM17、IFN、IL6、TNF-α等炎症介质,CXCR6可介导这一途径.ox-LDL激活MAPK信号转导通路,使p38、ERK1/2、SAPK/JNK的磷酸化水平升高,激活了NF-κB p65的活性,CXCR6-CXCL16介导MAPK信号途径.

Experimental study of renal injury induced by oxidized low-density lipoprotein in Nephrotic Syndrome

Objective Oxidized low density lipoprotein （ox-LDL） induced MCs secretion of inflammatory cytokines and mitogen-activated protein kinase （MAPK） signaling pathway and NF-κB protein phosphorylation levels to clarify the mechanism of action of lipids on renal injury. Methods Ox-LDL-induced proliferation of rat mesangial cells were detected the levels of the inflammatory cytokines , MAPK signal transduction pathway（p38,JNK,ERK） and NF-κB. by molecular biology techniques such as ELISA. real-time PCR, western blot. Results Ox-LDL-induced proliferation of rat mesangial cells, the levels of inflammatory cytokines （CXCL16, CD36 , ADAM10, ADAM17, IFN, IL6, TNF-α） and phosphorylation levels of NF-κB p65, p38. ERK1 /2. SAPK/JNK were significantly increased（P〈0. 01）, after adding CXCR6 receptor the levels further increased. Conclusions Ox-LDL may promote the release of inflammatory mediators such as CXCL16, CD36 , ADAM 10 , ADAM17 in mesangial cells , CXCR6 may mediated this path. ox-LDL activates the MAPK signal transduction pathway, the p38, ERK1/2, SAPK/JNK phosphorylation levels increased, activated NF-κB p65, CXCR6- CXCL16 mediated MAPK signaling pathways.