小檗碱抵抗压力超负荷大鼠心肌肥厚的作用及其机制  

Effects and mechanism of Berberine in resisting myocardial hypertrophy in pressure overloaded rats

作　　者：王家璞 张晓娟 介希 许慧玉 王科 朱宗凤 Wang Jiapu;Zhang Xiaojuan;Jie Xi;Xu Huiyu;Wang Ke;Zhu Zongfeng(Laboratory,Shanxi Province Cardiovascular Hospital,Shanxi Province Cardiovascular Institute,Affiliated Cardiovascular Hospital of Shanxi Medical University,Taiyuan,Shanxi 030024,China;Department of Cardiology,Shanxi Province Cardiovascular Hospital,Shanxi Province Cardiovascular Institute,Affiliated Cardiovascular Hospital of Shanxi Medical University,Taiyuan,Shanxi 030024,China)

机构地区：[1]山西省心血管病医院,山西省心血管病研究所,山西医科大学附属心血管病医院实验室,山西太原030024 [2]山西省心血管病医院,山西省心血管病研究所,山西医科大学附属心血管病医院心内科,山西太原030024

出　　处：《中国药物与临床》2024年第6期348-352,共5页Chinese Remedies & Clinics

基　　金：山西省应用基础研究计划面上自然科学基金项目(201901D111444);山西省心血管病医院科研激励计划项目(XYS20180101、XYS20190104)。

摘　　要：目的观察小檗碱抵抗压力超负荷大鼠心肌肥厚的作用及其可能机制。方法40只SD大鼠通过腹主动脉缩窄术建立压力超负荷心肌肥厚模型,术后分为4组:假手术组(sham组)、压力超负荷手术组(AAC组)、AAC+小檗碱组、AAC+小檗碱+自噬抑制剂3-甲基嘌呤(3-MA)组。术后观察4周采用小动物超声测心功能,蛋白质印迹实验测凋亡相关因子B细胞淋巴瘤因子2蛋白(bcl-2)和凋亡蛋白(bax)表达、自噬相关蛋白beclin1表达、信号通路相关哺乳动物雷帕霉素靶蛋白(mTOR)和磷酸化mTOR(p-mTOR)表达。结果与sham组相比,AAC组的左心室收缩末期内径(LVESD)为(4.80±0.32)mm、左心室舒张末期内径(LVEDD)为(5.97±0.18)mm、bax/bcl-2比值为(1.31±0.06)、p-mTOR/mTOR比值为(1.20±0.07),均高于sham组,左心室射血分数(LVEF)为(50.90±1.71)%、左心室缩短分数(LVFS)为(34.87±0.45)%,均低于sham组,差异均有统计学意义(P<0.05),但是beclin1/GAPDH减少差异无统计学意义。与AAC组相比,AAC+小檗碱组的LVESD为(4.33±0.10)mm、LVEDD为(4.91±0.55)mm、bax/bcl-2比值为0.81±0.07、p-mTOR/mTOR比值为1.07±0.03,均低于AAC组,LVEF为(56.32±1.44)%、LVFS为(40.71±0.94)%、beclin1/GAPDH比值为1.59±0.04,均高于AAC组,差异均有统计学意义(P<0.05)。与AAC+小檗碱组相比,AAC+小檗碱+3MA组的LVEDD为(5.82±0.19)mm、bax/bcl-2比值为(1.28±0.04),均高于AAC+小檗碱组,而LVEF为(52.44±0.57)%、LVFS为(37.14±0.34)%、beclin1/GAPDH比值为(1.32±0.08),均低于AAC+小檗碱组,差异均有统计学意义(P<0.05)。结论小檗碱通过自噬增强来抵抗AAC大鼠心肌肥厚,降低心肌细胞凋亡水平,其机制与抑制mTOR有关。Objective To observe the effects and possible mechanisms of Berberine in resisting cardiac hypertrophy in pressure-overloaded rats.Methods Forty SD rats were established as pressure overload cardiac hypertrophy model by abdominal aortic constriction(AAC),and were randomly divided into 4 groups after surgery:sham group,pressure overload surgery group(AAC group),AAC+berberine group,and AAC+berberine+3-MA group.After 4 weeks,Cardiac index was calculated by postoperative observation;cardiac function was measured by small animal ultrasound;apoptosis-related factors bcl-2 and bax expression,autophagy-related protein beclin1 expression and signaling pathway-related mTOR and p-mTOR expression were measured by Western blot.Results Compared with the sham group,the left ventricular end-systolic internal diameter(LVESD)of the AAC group was(4.80±0.32)mm,the left ventricular end-diastolic internal diameter(LVEDD)of the AAC group was(5.97±0.18)mm,the bax/bcl-2 ratio of the AAC group was(1.31±0.06),the p-mTOR/mTOR ratio of the AAC group was(1.20±0.07),which were higher than that of the sham group;the left ventricular ejection fraction(LVEF)was(50.90±1.71)%and left ventricular shortening fraction(LVFS)was(34.87±0.45)%,which were lower than sham group,and the differences were statistically significant(P<0.05),but the difference in beclin1/GAPDH reduction was not statistically significant.Compared with the AAC group,the LVESD was(4.33±0.10)mm,LVEDD was(4.91±0.55)mm,bax/bcl-2 ratio was(0.81±0.07),p-mTOR/mTOR ratio was(1.07±0.03),which were lower than that of the AAC group;and the LVEF was(56.32±1.44)%,LVFS was(40.71±0.94)%and beclin1/GAPDH ratio was(1.59±0.04)in the AAC+berberine group,which were higher than that of the AAC group and the differences were all statistically significant(P<0.05).Compared with the AAC+berberine group,the LVEDD was(5.82±0.19)mm and bax/bcl-2 ratio was(1.28±0.04),which were higher in the AAC+berberine+3-MA group than that in the AAC+berberine group;whereas the LVEF was(52.44±0.57)%,LVFS was

关 键 词：小檗碱 心肌肥厚 自噬 凋亡 

分 类 号：R285.5[医药卫生—中药学]