毛冬青皂苷A改善高脂血症发挥心脏保护作用的研究  

Study on mechanism of cardioprotective effect of Ilexin A in improving hyperlipidemia

作　　者：张颖[1] 孙理华 时司宴 王维浩 彭海军[2] ZHANG Ying;SUN Li-hua;SHI Si-yan;WANG Wei-hao;PENG Hai-jun(Department of Hypertension,Heart Center,FifthAffliated Hospital of Xinjiang Medical University,Urumqi 83001l,Xinjiang UygurAutonomous Region,China;Departmentof Cardiovascular Medicine,Zhongshan Boai Hospital,Southern Medical University,Zhongshan 528403,Guangdong Province,China)

机构地区：[1]新疆医科大学第五附属医院心脏中心高血压科,新疆维吾尔自治区乌鲁木齐830011 [2]南方医科大学附属中山市博爱医院心血管内科,广东中山528403

出　　处：《中国临床药理学杂志》2025年第5期686-690,共5页The Chinese Journal of Clinical Pharmacology

基　　金：新疆维吾尔自治区自然科技基金资助项目(2018D01C300);中山市社会公益科技研究基金资助项目(2023B1059)。

摘　　要：目的探讨毛冬青皂苷A通过调节微小RNA-133a-3p(miR-133a-3p)及解偶联蛋白2(UCP2)改善高脂血症发挥心脏保护作用的机制。方法将大鼠随机分为对照组(灌胃与实验组等量蒸馏水)、模型组(灌胃与实验组等量蒸馏水)、实验组(灌胃40 mg·kg^(-1)毛冬青皂苷A)、miR-133a-3p inhibitor组(灌胃40 mg·kg^(-1)毛冬青皂苷A+尾静脉注射1.95×1012 vg·mL^(-1)含有miR-133a-3p抑制剂的腺病毒)、OE-UCP2组(灌胃40 mg·kg^(-1)毛冬青皂苷A+尾静脉注射1.95×10^(12)vg·mL^(-1)含有miR-133a-3p抑制剂和含有OE-UCP2的腺病毒)。用酶联免疫吸附试验检测血脂水平指标[低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)等],用心脏彩超测定心功能指标[舒张期早期血流速度E与晚期A的比值(E/A)、左心室射血分数(LVEF)等],用实时荧光定量聚合酶链反应检测mRNA相对表达水平,用蛋白质印迹法检测蛋白相对表达水平。结果模型组和实验组的LDL-C水平分别为(0.92±0.12)和(0.76±0.09)mmol·L^(-1),HDL-C水平分别为(0.82±0.10)和(1.14±0.13)mmol·L^(-1),E/A分别为0.89±0.11和1.17±0.14,LVEF分别为(41.31±5.07)%和(59.92±7.86)%,miR-133a-3p相对表达水平分别为0.33±0.06和1.22±0.18,解偶联蛋白2(UCP2)mRNA相对水平分别为0.57±0.08和0.79±0.09,裂解的胱天蛋白酶3(Cleaved caspase-3)蛋白相对表达水平分别为1.00±0.15和0.71±0.09,B淋巴细胞瘤-2基因(Bcl-2)蛋白相对表达水平分别为1.00±0.17和1.94±0.27,模型组的上述指标与实验组比较,在统计学上差异有统计学意义(均P<0.05)。结论毛冬青皂苷A可通过调节miR-133a-3p及UCP2改善高脂血症,其机制可能与下调Bcl-2,激活Cleaved caspase-3诱导细胞凋亡相关,可发挥心脏保护作用,改善心功能。Objective To investigate the cardioprotective mechanism of Ilexin A in ameliorating hyperlipidemia through the regulation of microRNA-133a-3p(miR-133a-3p)and uncoupling protein 2(UCP2).Methods Rats were randomly divided into control group(gavage with an equal volume of distilled water as the experimental group),model group(gavage with an equal volume of distilled water as the experimental group),experimental group(gavage with 40 mg·kg^(-1)Ilexin A),miR-133a-3p inhibitor group(gavage with 40 mg·kg^(-1)Ilexin A+tail vein injection of 1.95×10^(12)vg·mL^(-1)adenovirus containing miR-133a-3p inhibitor),and OE-UCP2 group(gavage with 40 mg·kg^(-1)Ilexin A+tail vein injection of 1.95×10^(12)vg·mL^(-1)adenovirus containing both miR-133a-3p inhibitor and OE-UCP2).Blood lipid levels,including low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C),were measured by enzymelinked immunosorbent assay.Cardiac function parameters,such as the mitral inflow peak early diastolic velocity to late diastolic velocities(E/A)and left ventricular ejection fraction(LVEF),were assessed via echocardiography.The relative expression levels of mRNA were analyzed by real-time quantitative polymerase chain reaction(RT-qPCR),while protein levels were detected by Western blot.Results In the model and experimental groups,LDL-C levels were(0.92±0.12)and(0.76±0.09)mmol·L^(-1);HDL-C levels were(0.82±0.10)and(1.14±0.13)mmol·L^(-1);E/A ratios were 0.89±0.11 and 1.17±0.14;LVEF values were(41.31±5.07)%and(59.92±7.86)%;the relative expression levels ofmiR-133a-3pwere 0.33±0.06 and 1.22±0.18;uncoupling protein 2(UCP2)mRNA levels were 0.57±0.08 and 0.79±0.09;cleaved caspase-3 protein levels were 1.00±0.15 and 0.71±0.09;B-cell lymphoma-2(Bcl-2)protein levels were 1.00±0.17 and 1.94±0.27,respectively.The differences between the model and experimental groups for these parameters were statistically significant(allP<0.05).Conclusion Ilexin A ameliorates hyperlipidemia by regulatingmiR-133a-3pand UCP2.Its m

关 键 词：毛冬青皂苷A 解偶联蛋白2 高脂血症 心脏保护作用 凋亡蛋白 

分 类 号：R285.5[医药卫生—中药学]