肾康灵对氧化低密度脂蛋白诱导系膜细胞增殖后 MAPK 信号通路的影响  

Effect of Shenkangling on MAPK Signaling Pathway After Ox-LDL-Induced MC Proliferation

作　　者：艾斯[1,2] 郑健[1,2] 林青[1] 褚克丹[2] 潘旭东[1] 林雄[1] 

机构地区：[1]福建中医药大学附属人民医院 [2]福建中医药大学

出　　处：《中医杂志》2014年第8期691-694,共4页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81202835);福建省自然科学基金资助项目(2011J01199);福建省卫生厅青年基金资助项目(2012-1-30)

摘　　要：目的探讨肾康灵干预小儿原发性肾病综合征(PPNS)的作用机制。方法将诱导系膜细胞(MCs)随机分为正常对照组、氧化低密度脂蛋白(ox-LDL)组、ox-LDL+CXCR6(CXCL16受体CXCR6)组、肾康灵低浓度组(1.5g/ml)、肾康灵高浓度组(3.0g/ml)、阿托伐他汀低浓度组(50μmol/L)、阿托伐他汀高浓度组(100μmol/L),观察各组MCs的CXCL16、CD36蛋白含量、MAPK信号通路相关蛋白(p38、ERK1/2、SAPK/JNK)及核因子-κB p65(NF-κB p65)的磷酸化水平。结果 ox-LDL+CXCR6组较正常对照组CXCL16、CD36蛋白含量、MAPK信号通路相关蛋白(p38、ERK1/2、SAPK/JNK)及NF-κB p65的磷酸化水平显著升高(P<0.01);与ox-LDL组及ox-LDL+CXCR6组比较,肾康灵低、高浓度组及阿托伐他汀低、高浓度组的CXCL16、CD36蛋白含量、p38、SAPK/JNK、NF-κB p65的磷酸化水平显著降低(P<0.01),肾康灵低、高浓度组及阿托伐他汀高浓度组的ERK1/2的磷酸化水平显著降低(P<0.05或P<0.01);肾康灵高浓度组CXCL16、CD13蛋白含量、SAPK/JNK、NF-κB p65的磷酸化水平明显低于阿托伐他汀低浓度组(P<0.05)。结论肾康灵可能通过抑制MAPK信号通路相关蛋白(p38、ERK1/2、SAPK/JNK)、NF-κB p65及CXCL16、CD36,有效抑制MCs的增殖,从而实现减轻或延缓肾小球纤维化的作用。Objective To observe the effect of Shenkangling on MAPK signaling pathway after oxidized low- density lipoprotein （ox-LDL） -induced mesangial cell （MC） proliferation and study the mechanism. Methods The MCs were randomized into the normal control group, ox-LDL group, ox-LDL ＋ CXC-chemokine receptor 6 （CXCR6） group, Shenkangling low-concentration and high-concentration groups, and atorvastatin low-concentration and high-concentration groups. The protein contains of C-X-C chemokine ligand 16 （CXCL16） and CD36 and the phosphorylation levels of p38, ERK1/2, SAPK/JNK and nuclear factor-κB （NF-κB） p65 of MCs in all groups were observed. Results Comparing with the normal control group, the protein contains of CXCL16 and CD36 and the phosphorylation levels of p38, ERK1/2, SAPK/JNK and NF-KB p65 of MCs in the ox-LDL ＋ CXCR6 group were significantly increased （P 〈0.01 ）. Comparing with the ox-LDL ＋ CXCR6 group, the protein contains of CXCL16 and CD36 and the phosphorylation levels of p38, SAPK/JNK and NF-κB p65 of MCs were significantly decreased in the Shenkangling groups and atorvastatin groups （P 〈0.01 ） , and the phosphorylation level of ERK1/2 was significantly decreased in the Shenkangling groups and atorvastatin high-concentration group （P 〈 0.05 or P 〈 0.01 ）. The protein contain of CXCL16 and the phosphorylation levels of SAPK/JNK and NF-κB p65 in the Shenkangling high-concentration group were significantly lower than those in the atorvastatin low-concentration group （ P 〈 0.05 or P 〈 0.01 ）. Conclusion Shenkangling can effectively inhibit the proliferation of MCs possibly by inhibiting the proteins such as p38, ERK1/2 and SAPK/JNK associated with MAPK singling pathway, NF-κB p65, CXCL16 and CD36.

关 键 词：肾康灵 系膜细胞 氧化低密度脂蛋白 MAPK信号通路 核因子-ΚB 

分 类 号：R285.5[医药卫生—中药学]