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.