色素上皮衍生因子抑制人肾小球系膜细胞基质金属蛋白酶沉积及机制探讨  

Pigment epithelial-derived factors inhibit the deposition of matrix metalloproteinases in human glomeruli mesangial cells and its mechanism

作　　者：盛霞[1] 胡玲[1] 熊国辉 朱艳[1] 熊累累 尹晓玲 SHENG Xia;HU Ling;XIONG Guohui(Department of Endocrinology and Metabolism,Third Affiliated Hospital of Nanchang University,Nanchang 330008,China)

机构地区：[1]南昌大学第三附属医院内分泌代谢科,330008 [2]南昌市洪都中医院骨质疏松科

出　　处：《中国糖尿病杂志》2020年第12期933-937,共5页Chinese Journal of Diabetes

摘　　要：目的观察重组色素上皮衍生因子(PEDF)对基质金属蛋白酶9(MMP-9)、基质金属蛋白酶抑制剂1(TIMP-1)、磷酸化p38丝裂原活化蛋白激酶(P-p38MAPK)表达的影响,探讨PEDF对DKD的保护机制。方法糖化牛血清白蛋白(BSA,AGEs 200 mg/L)体外诱导人肾小球系膜细胞(HRMCs),分为空白对照组(NC)、BSA组、AGEs组、AGEs+PEDF 5组、AGEs+PEDF 20组、AGEs+PEDF 40组、AGEs+SB203580 10组。半定量聚合酶连反应(RT-PCR)检测MMP-9、TIMP-1 mRNA表达,Western blot法检测P-p38MAPK、MMP-9、TIMP-1蛋白表达。结果 AGEs组MMP-9蛋白和mRNA表达水平低于其他组(P<0.05),TIMP-1蛋白和mRNA、P-p38MAPK蛋白表达水平高于其他组(P<0.05)。PEDF呈浓度依赖性升高AGEs介导的MMP-9 mRNA和蛋白低表达(P<0.05),降低TIMP-1 mRNA和蛋白及P-p38MAPK蛋白在HRMCs的高表达(P<0.05)。结论 PEDF可能通过抑制AGEs-p38MAPK信号通路改善MMP-9、TIMP-1在HRMCs的表达,发挥DKD保护作用。Objective To observe the effect of recombinant pigment epithelial-derived factor(PEDF)on the expression of matrix metalloproteinase 9(MMP-9),matrix metalloproteinase-inhibitor 1(TIMP-1)and phosphorylated p38 MAPK(P-p38 MAPK),and to explore the protective mechanism of PEDF on diabetic kidney disease(DKD).Methods Human glomerular mesangial cells(HRMCs)were induced by AGEs 200 mg/L and divided into 7 groups,including NC group,BSA group,AGEs group,AGEs+PEDF5 group,AGEs+PEDF20 group,AGEs+PEDF40 group,AGEs+SB203580 group.The m RNA expressions of MMP-9 and TIMP-1 were detected by semi-quantitative polymerase chain reaction(RT-PCR).The protein expressions of P-p38 MAPK,MMP-9 and TIMP-1 were detected by Western blot.Results The expression levels of MMP-9 protein and m RNA in AGEs group were lower than those in other groups(P<0.05).The expression levels of TIMP-1 protein,m RNA and P-p38 MAPK protein were higher than those in other groups(P<0.05).In a concentration dependent manner,PEDF increased the expression level of MMP-9 m RNA and protein mediated by AGEs(P<0.05),and decreased the expression level of TIMP-1 and P-p38 MAPK protein mediated by AGEs in HRMCs(P<0.05).Conclusion PEDF may partially improve the expression of MMP-9 and TIMP-1 in HMCs by inhibiting the AGEs-p38 MAPK signaling pathway,which may play a protective role in DKD.

关 键 词：色素上皮衍生因子 晚期糖基化终产物 糖尿病肾脏疾病 基质金属蛋白酶9 基质金属蛋白酶抑制剂1 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]