mmLDL通过p38 MAPK通路上调小鼠肠系膜动脉ET受体

目的:探讨弱氧化修饰低密度脂蛋白(mm LDL)是否通过激活p38 MAPK炎症通路上调小鼠肠系膜动脉内皮素(ET)A型(ET_A)和B型(ET_B)受体。方法:将昆明小鼠分为正常对照组(尾静脉注射生理盐水)、mm LDL组(尾静脉注射mm LDL)、LDL组(尾静脉注射LDL)、mm LDL+SB 203580组(尾静脉注射mm LDL及腹腔注射p38 MAPK抑制剂SB 203580)和mm LDL+DMSO组(尾静脉注射mm LDL及腹腔注射DMSO)。微血管张力描记仪记录ET_B受体激动剂角蝰毒素6c和ET-1引起肠系膜动脉收缩的量效曲线;RT-q PCR检测ET_B受体、ET_A受体和白细胞介素(IL-6)的m RNA表达;ELISA检测血清IL-6的水平;Western blot检测ET_B受体、ET_A受体、IL-6、p38 MAPK、p-p38MAPK、NF-κB和p-NF-κB的蛋白水平。结果:mm LDL引起ET_B

Minimally modified low-density lipoprotein up-regulates endothelin receptors in mouse mesenteric artery through p38 MAPK pathway

AIM:To investigate whether minimally modified low-density lipoprotein(mm LDL)affects the quantity and activity of endothelin(ET)type A(ETA)and type B(ETB)receptors in mouse mesenteric artery by activating p38 mitogen-activated protein kinase(MAPK)inflammatory pathway.METHODS:The KM mice were divided into normal saline(NS)group(injection of NS via caudal vein),mm LDL group(injection of mm LDL via caudal vein),LDL group(injection of LDL via caudal vein),mm LDL+SB 203580 group(injection of mm LDL via caudal vein and intraperitoneal injection of p38 MAPK pathway specific inhibitor SB 203580)and mm LDL+DMSO group(injection of mm LDL via caudal vein and intraperitoneal injection of DMSO).Mesenteric artery ring segment vasoconstriction dose-response curves affected by sarafotoxin 6c(S6c)and ET-1 were recorded by the myography system.The m RNA levels of ETBreceptor,ETAreceptor and interleukin-6(IL-6)were detected by RT-q PCR.The protein levels of ETBreceptor,ETAreceptor,IL-6,p38 MAPK,p-p38 MAPK,NF-κB and p-NF-κB were determined by Western blot.The serum concentration of IL-6was measured by ELISA.RESULTS:The contractile responses of the blood vessel segments to S6c and ET-1 were significantly increased by mm LDL(P<0.01).The m RNA and protein expression levels of ETAreceptor,ETBreceptor,and IL-6significantly increased(P<0.01).The protein levels of p-p38 MAPK and p-NF-κB were significantly increased(P<0.01).The serum level of IL-6 was significantly increased(P<0.01).These effects of mm LDL were inhibited by p38MAPK inhibitor SB 203580.CONCLUSION:mm LDL increses the serum concentration of IL-6,up-regulates the expression of IL-6,ETAreceptor and ETBreceptor in mouse mesenteric artery,and enhances the vasoconstriction function mediated by ETAand ETBreceptors,which is related to the activation of p38 MAPK inflammatory pathway and downstream NF-κB pathway.