不同饱和度脂肪酸与足细胞损伤关系及损伤机制  

Relationship between different saturated fatty acids and podocyte injury and its mechanism

作　　者：丁晓华[1] 聂晓晶[1] 李莉 马雷[2] 杨勇辉[1] 赵锋[1] 谢婷婷[1] 张勇[3] 

机构地区：[1]南京军区福州总医院儿科(厦门大学附属东方医院儿科、福建医科大学福总临床医学院儿科),福建福州350025 [2]南京军区福州总医院比较医学科 [3]南京军区福州总医院肾内科

出　　处：《中华生物医学工程杂志》2016年第3期177-183,共7页Chinese Journal of Biomedical Engineering

基　　金：国家自然科学基金（81300583）;福建省自然科学基金（2014J05096）;中国博士后科学基金（2014M552705）;2013-2014年福建高层次人才访学研修资助（闽人办201376号）

摘　　要：目的：探讨不同饱和度脂肪酸与足细胞损伤的关系及相应的损伤机制。方法不同饱和度脂肪酸（棕榈酸、油酸、20碳5烯酸）分别干预足细胞，MTT法测足细胞存活率、免疫荧光检测足细胞骨架，从而判断足细胞是否损伤；Western印迹检测p38、细胞外信号调节激酶（ERK）1/2和氨基末端激酶（JNK）变化，RT-PCR检测COX-2和TNF-α，探讨相应损伤机制。结果经脂肪酸处理10 h，饱和脂肪酸棕榈酸组和对照组的细胞存活率分别为（66.96±2.41）%和（90.95±5.37）%（P〈0.05）；棕榈酸组丝状肌动蛋白（F-actin）较其他实验组减少；棕榈酸组p38、ERK1/2和JNK磷酸化水平升高，棕榈酸组与对照组的p-p38/p38、p-ERK/ERK和p-JNK/JNK差异均存在统计学意义（P〈0.05）；棕榈酸组COX-2和TNF-α表达升高，与对照组比较差异有统计学意义（P〈0.05）。4-8 h期间，单不饱和脂肪酸油酸可提高足细胞存活率。结论饱和脂肪酸棕榈酸可损伤足细胞，MAPK信号通路介导该损伤过程， MAPK信号通路中的p38、ERK1/2和JNK出现活化，并介导炎症因子COX-2和TNF-α产生；不饱和脂肪酸油酸可短期提高足细胞活力。Objective To investigate the relationship between different saturated fatty acids and podocyte injury and the corresponding injury mechanism. Methods The podocytes were intervened by different saturated fatty acids（palmitate,oleate and eicosapentaenoic acid）,respectively. The viability and cytoskeleton of podocytes were determined by MTT method and immunofluorescence to determine whether the podocytes were injured. The changes of MAPK signaling pathways（p38,ERK1/2 and JNK）were determined by Western blot. RT-PCR was used to determine COX-2 and TNF-α,and the corresponding injury mechanism was investigated. Results After 10h of fatty acid treatment,the cell viability in the palmitate （saturated fatty acid）group and the control group were（66.96 ± 2.41）%and（90.95 ± 5.37）%,respectively （P〈0.05）. The filamentous actin（F-actin）in the palmitate group was decreased compared with other study groups. The phosphorylation levels of p38,ERK1/2 and JNK in the palmitate group were increased. There were significant differences in p-p38/p38,p-ERK/ERK and p-JNK/JNK between the palmitate group and the control group（P〈0.05）. The expression levels of COX-2 and TNF-αwere increased in the palmitate group, and there were statistically significant differences compared with those in the control group（P〈0.05）. During 4-8 h,monounsaturated fatty acid can increase the viability of podocytes. Conclusions Palmitate（saturated fatty acid）may induce podocyte injury,which is mediated by MAPK signal pathway. The p38,ERK1/2 and JNK in the MAPK signal pathway are activated,which mediate the production of inflammatory cytokines COX-2 and TNF-α. Oleate（unsaturated fatty acid）can improve the viability of podocytes in a short time.

关 键 词：肾疾病 足细胞 高脂血症 游离脂肪酸 棕榈酸 

分 类 号：R692[医药卫生—泌尿科学]