外源性GDF11通过调控LOX-1介导的内质网应激途径改善高血压大鼠血管重构  

Exogenous GDF11 improves vascular remodeling in hypertensive rats by regulating LOX-1-mediated endoplasmic reticulum stress pathway

作　　者：戴正东[1] 胡良坤 万伟[1] 徐丽新 DAI Zhengdong;HU Liangkun;WAN Wei;XU Lixin(Macheng People s Hospital,Huanggang,Hubei 438300,China)

机构地区：[1]麻城市人民医院,湖北省黄冈市438300

出　　处：《中国动脉硬化杂志》2024年第10期850-856,共7页Chinese Journal of Arteriosclerosis

基　　金：湖北省卫生健康委员会基金项目(WJ2019F067)。

摘　　要：[目的]探讨外源性生长分化因子11(GDF11)通过调控凝集素样氧化型低密度脂蛋白受体1(LOX-1)介导的内质网应激途径对高血压大鼠血管重构的影响。[方法]将大鼠随机分为对照组、模型组(AngⅡ诱导的高血压大鼠模型组)、r-GDF11组、Ab-LOX-1组和r-GDF11+r-LOX-1组,每组10只。采用动物无创血压仪检测大鼠尾动脉血压变化;HE染色评估主动脉血管形态;Masson染色评估主动脉组织胶原沉积情况;Western blot检测主动脉组织中GDF11、LOX-1及内质网应激相关蛋白表达。[结果]与对照组比较,模型组大鼠血压升高,主动脉组织中膜厚度(MT)、MT/管腔内径(LD)比值增大,LD减小(均P<0.05);主动脉组织胶原纤维容积分数(CVF)值、葡萄糖调节蛋白78(GRP78)和转录激活因子6(ATF6)蛋白表达、磷酸化PKR样内质网调节激酶(p-PERK)/PERK和磷酸化肌醇需求酶1α(p-IRE1α)/IRE1α比值均升高(均P<0.05)。与模型组比较,r-GDF11组和Ab-LOX-1组大鼠血压降低,主动脉组织MT、MT/LD均减小,LD增大(均P<0.05);主动脉组织CVF值、GRP78和ATF6蛋白表达、p-PERK/PERK和p-IRE1α/IRE1α比值均显著降低(均P<0.05)。与r-GDF11组比较,r-GDF11+r-LOX-1组大鼠血压升高,主动脉组织MT、MT/LD增大,LD减小(均P<0.05);主动脉组织CVF值、GRP78和ATF6蛋白表达、p-PERK/PERK和p-IRE1α/IRE1α比值显著升高(均P<0.05)。[结论]外源性GDF11通过抑制LOX-1介导的内质网应激途径改善高血压大鼠血管重构。Aim To investigate the effect of exogenous growth differentiation factor 11(GDF11)on vascular remodeling in hypertensive rats through regulating the endoplasmic reticulum stress pathway mediated by lectin-like oxidized low density lipoprotein receptor-1(LOX-1).Methods Rats were randomly divided into control group,model group(AngⅡ-induced hypertension rat model group),r-GDF11 group,Ab-LOX-1 group,r-GDF11+r-LOX-1 group,with 10 rats in each group.The changes of caudal arterial blood pressure in rats were detected by animal non-invasive blood pressure meter;the morphology of aortic vessels was evaluated by hematoxylin-eosin(HE)staining;the collagen deposition in aortic tissue was evaluated by Masson staining;the expression of GDF11,LOX-1 and endoplasmic reticulum(ER)stress related proteins in aortic tissues were detected by Western blot.Results Compared with the control group,the blood pressure of rats in the model group was increased,the media thickness(MT)and MT/lumen diameter(LD)of aortic tissue were increased,and the LD of aortic tissue was decreased(all P<0.05);Collagen volume fraction(CVF)value,the expression of glucose regulated protein 78(GRP78)and activating transcription factor 6(ATF6)protein,the ratio of phosphorylated PKR-like endoplasmic reticulum regulating kinase(p-PERK)/PERK and phosphorylated inositol requiring enzyme 1α(p-IRE1α)/IRE1αin aortic tissue were increased(all P<0.05).Compared with the model group,the blood pressure of rats in the r-GDF11 group and Ab-LOX-1 group was decreased,the MT and MT/LD of aortic tissue were decreased,and the LD of aortic tissue was increased(all P<0.05);CVF value,the expression of GRP78 and ATF6 protein,p-PERK/PERK and p-IRE1α/IRE1αin aortic tissue were decreased(all P<0.05).Compared with the r-GDF11 group,the blood pressure of rats in the r-GDF11+r-LOX-1 group was increased,the MT and MT/LD of aortic tissue were increased,and the LD of aortic tissue was decreased(all P<0.05);CVF value,the expression of GRP78 and ATF6 protein,the p-PERK/PERK and p-IRE1α/IRE1

关 键 词：外源性生长分化因子11 高血压 血管重构 凝集素样氧化型低密度脂蛋白受体1 内质网应激 

分 类 号：R5[医药卫生—内科学] R363[医药卫生—临床医学]