PTEN诱导激酶1在高血压小鼠主动脉硬化中的机制研究  

Role of PTEN-induced putative kinase 1 in aortic arteriosclerosis in mouse model of hypertension

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作  者:吉律 刘旭勤 土旦 石宁宁 曲央旺姆 周吴刚[2] JI Lü;LIU Xuqin;TU Dan;SHI Ningning;QU Yangwangmu;ZHOU Wugang(Department of Critical Care Medicine,Shigatse People’s Hospital,Shigatse 857000,Xizang,China;不详)

机构地区:[1]日喀则市人民医院重症医学科,西藏自治区日喀则市857000 [2]上海交通大学医学院附属第九人民医院急诊科

出  处:《上海医学》2023年第11期758-765,共8页Shanghai Medical Journal

基  金:西藏自治区自然科学基金联合项目(XZ202101ZR0011G);西藏自治区自然科学基金组团式医学援藏项目(XZ2020ZR-ZY40(Z))。

摘  要:目的 探讨PTEN诱导激酶1(PINK1)在高血压模型小鼠主动脉硬化中的作用及其对血管重塑的机制。方法取8~10周龄C57BL/6J雄性小鼠12只,随机分为阴性对照组和高血压造模组,每组6只,于皮下埋植微渗透泵缓慢释放血管紧张素(Ang)Ⅱ以诱导高血压小鼠模型。取8~10周龄野生型C57BL/6J雄性小鼠24只,随机分为空白对照组、假手术组、高血压模型组、PINK1处理组4组,每组6只。空白对照组,假手术组小鼠予0.9%氯化钠溶液(灌泵)+pLenti-NC(腹腔内注射),高血压模型组小鼠予AngⅡ(灌泵)+pLenti-NC (腹腔内注射),PINK1处理组小鼠予AngⅡ(灌泵)+pLenti-PINK1(腹腔内注射)。利用BP98A鼠尾套管无创血压仪监测血压变化,采用“点对点”法监测主动脉脉搏波传导速度(PWV),测定血清IL-1β、IL-6和TNF-α水平,H-E染色观察主动脉组织结构,Western印迹法分析PINK1、CollagenⅠ、LC3B-Ⅱ、p62蛋白质相对表达量,免疫荧光染色观察CollagenⅠ表达。结果 构建小鼠模型的收缩压监测结果显示:灌注后第1~8天和第10、12、14天,高血压造模组小鼠的收缩压均显著高于阴性对照组(P值均<0.01);灌注第14天,阴性对照组小鼠PWV显著短于高血压造模组(P<0.05);Western印迹法检测结果显示,阴性对照组PINK1相对表达量显著高于高血压造模组(P<0.05);阴性对照组的CollagenⅠ相对表达量显著低于高血压造模组(P<0.01)。PINK1回补实验结果显示:灌注后第3~8天和灌注后第10、12、14天,PINK1处理组小鼠收缩压显著低于高血压模型组(P值均<0.01);PINK1处理组小鼠的PWV显著短于高血压模型组小鼠(P<0.01)。高血压模型组小鼠血清IL-1β、IL-6和TNF-α水平均显著高于假手术组(P值均<0.001),PINK1处理组IL-1β、IL-6和TNF-α水平均显著低于高血压模型组(P值均<0.01)。Western印迹法检测结果显示,与假手术组及空白对照组比较,高血压模型组中PINK1、LC3B-Ⅱ蛋白质相对表达量均显著降低(PObjective To investigate the role of PTEN-induced putative kinase 1(PINK1)in arteriosclerosis in a mouse model of hypertension and its impact on vascular remodeling.Methods Twelve C57BL/6J male mice aged from 8-10 weeks were randomly divided into negative control group and hypertension model group,with 6 mice in each group.C57BL/6J mice were subcutaneously implanted with osmotic pump to slowly release AngⅡto induce hypertensive mouse model.Twenty-four wild-type C57BL/6J male mice aged 8-10 weeks were randomly divided into 4 groups:control group,sham operation group,hypertension model group and PINK1-treated group with 6 mice in each group.The mice in the control group and sham operation group were treated with 0.9%sodium chloride(pump)+pLenti-NC(intraperitoneal injection).The mice in the hypertension model group were treated with AngⅡ(pump)+pLenti-NC(intraperitoneal injection).The mice in the PINK1-treated group were given AngⅡ(pump)+pLenti-PINK1(intraperitoneal injection).The blood pressure was monitored by BP98A rat tail cannula non-invasive blood pressure monitor.The aortic pulse wave velocity(PWV)was measured by point-to-point method.The serum levels of IL-1β,IL-6 and TNF-αwere measured.The tissue structure of aorta was observed by H-E staining.The relative expression of PINK1,CollagenⅠ,LC3B-Ⅱand p62 protein was analyzed by Western blotting.The expression of CollagenⅠwas observed by immunofluorescence staining.Results The systolic blood pressure of the hypertension model group was significantly higher than that of the control group on day 1-8 and the 10th,12th and 14th days after AngⅡperfusion(all P<0.01).On the 14th day after AngⅡperfusion,PWV in the control group was significantly shorter than that in the hypertension model group(P<0.05).The results of Western blotting showed that the relative expression of PINK1 in the control group was significantly higher than that in the hypertension model group(P<0.05),and the relative expression of CollagenⅠin the control group was significantly lo

关 键 词:高血压 自噬 PTEN诱导激酶1 血管紧张素Ⅱ 动脉 硬化 

分 类 号:R692.5[医药卫生—泌尿科学]

 

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