首页|小檗碱抵抗压力超负荷大鼠心肌肥厚的作用及其机制

小檗碱抵抗压力超负荷大鼠心肌肥厚的作用及其机制

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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.
Effects and mechanism of Berberine in resisting myocardial hypertrophy in pressure overloaded rats
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(37.14±0.34)%and beclin1/GAPDH ratio was(1.32±0.08)in the AAC+berberine+3-MA group,which were lower than that in AAC+berberine group and the differences were all statistically significant(P<0.05).Conclusion Berberine resists cardiac hypertrophy and reduces cardiomyocyte apoptosis in AAC rats through autophagy enhancement,and its mechanism is related to the inhibition of mTOR.

BerberineCardiac hypertrophyAutophagyApoptosis

王家璞、张晓娟、介希、许慧玉、王科、朱宗凤

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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

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

小檗碱 心肌肥厚 自噬 凋亡

山西省应用基础研究计划面上自然科学基金山西省心血管病医院科研激励计划山西省心血管病医院科研激励计划

201901D111444XYS20180101XYS20190104

2024

中国药物与临床
中国医院协会

中国药物与临床

影响因子:0.846
ISSN:1671-2560
年,卷(期):2024.24(6)