CDR132L改善高血压合并高脂血症小鼠血管重构和功能  

CDR132L improves vascular remodeling and function in hypertensive combined with hyperlipidemia mice

作　　者：林俊敏[1] 梁风金 吴莹 许开祖[1] 吴梅芳[1] 林丽明[1] LIN Junmin;LIANG Fengjin;WU Ying;XU Kaizu;WU Meifang;LIN Liming(Department of Cardiology,Affiliated Hospital of Putian University&Clinical Medicine School of Fujian Medical University,Putian,Zhejiang 351100,China)

机构地区：[1]莆田学院附属医院心血管内科,福建医科大学临床医学院,福建省莆田市351100

出　　处：《中国动脉硬化杂志》2024年第4期303-309,共7页Chinese Journal of Arteriosclerosis

基　　金：福建省自然科学基金项目(2022J011433、2022J011431);国家自然科学基金青年项目(81800278)。

摘　　要：[目的]观察CDR132L(miR-132反义核苷酸)对高血压合并高脂血症小鼠血管重构和功能的影响,并探究其可能的作用机制。[方法]随机选择30只8周龄雄性C57BL/6小鼠,分为三组:对照组、模型组和CDR132L组,每组10只。对照组接受标准饲料喂养,模型组和CDR132L组给予N-硝基-L-精氨酸甲酯(L-NAME)和高脂食物联合喂养来诱导高血压和高脂血症。CDR132L组给予20 mg/kg CDR132L腹腔注射,1次/周,连续6周,对照组和模型组腹腔注射相同剂量的生理盐水溶液。尾套法测量小鼠尾动脉收缩压和舒张压,血脂、血糖检测由全自动生化分析仪完成,HE染色观察胸主动脉结构,血管环试验观察小鼠胸主动脉内皮依赖性舒张反应,定量基因扩增检测胸主动脉miR-132表达水平,Western blot检测胸主动脉Gab1和内皮型一氧化氮合酶(eNOS)蛋白表达水平。[结果]与对照组相比,模型组小鼠收缩压、舒张压、血清甘油三酯、血清总胆固醇和体质量均明显升高(P<0.05),胸主动脉内膜凹凸不平,血管壁厚度不均,中膜平滑肌细胞的排列呈现不规则状态,血管壁上存在大量脂肪积聚,胸主动脉内皮依赖性舒张反应减低(P<0.05),胸主动脉miR-132表达水平明显增加(P<0.05),Gab1和eNOS蛋白表达水平明显降低(P<0.05)。与模型组相比,CDR132L组小鼠收缩压、舒张压、血清甘油三酯、血清总胆固醇和体质量均无统计学差异(P>0.05),胸主动脉管腔内膜较完整光滑,血管壁厚度较均一,中膜平滑肌细胞的排列较为有序,血管壁仅存在少量脂肪积聚,胸主动脉内皮依赖性舒张反应增强(P<0.05),胸主动脉miR-132表达水平明显降低(P<0.05),Gab1和eNOS蛋白表达水平明显增加(P<0.05)。[结论]CDR132L能改善高血压合并高脂血症小鼠血管重构及内皮依赖性舒张功能,这一作用可能与其降低胸主动脉miR-132表达水平,进而上调胸主动脉Gab1和eNOS蛋白表达水平有关。Aim To investigate the effect of CDR132L(miR-132 antisense oligonucleotide)on vascular remodeling and function in mice with hypertension and hyperlipidemia,and explore its possible mechanism.Methods A total of 308-week-old male C57BL/6 mice were randomly divided into three groups:control group,model group and CDR132L group,with 10 mice in each group.The control group received with a standard diet while the model group and CDR132L group received N-nitro-L-arginine methyl ester(L-NAME)and high-fat diet to induce hypertension and hyperlipidemia.The CDR132L group was administered with intraperitoneal injection of CDR132L at a dose of 20 mg/kg once weekly for six consecutive weeks,whereas the control group and the model group were given intraperitoneal injection of an equivalent volume of normal saline.The tail-cuff method was utilized for blood pressure measurement,blood lipid and glucose levels were assayed by an automatic biochemical analyzer,the thoracic aorta structure was observed by HE staining,endothelium-dependent relaxation of the thoracic aorta was evaluated by the vascular ring test,the expression level of miR-132 in the thoracic aorta was measured by qPCR,the protein expression levels of Gab1 and endothelial nitric oxide synthase(eNOS)in the thoracic aorta were determined by Western blot.Results Compared with the control group,the model group demonstrated notable rises in systolic and diastolic blood pressure,serum triglyceride,total cholesterol levels,and body weight.Moreover,the intima of thoracic aorta and the thickness of vascular wall was uneven,the smooth muscle cells of the tunica media were arranged irregularly,with a large amount of fat deposition in the vascular wall,and the endothelium-dependent relaxation response of thoracic aorta was decreased(P<0.05).The expression level of miR-132 in the thoracic aorta was significantly increased(P<0.05),while the expression level of Gab1 and eNOS protein was markedly decreased(P<0.05).Compared with the model group,the CDR132L group showed no significant d

关 键 词：CDR132L miR-132 高血压 高脂血症 血管重构 内皮舒张功能 

分 类 号：R363[医药卫生—病理学] R5[医药卫生—基础医学]