The Effects Of Berberine On Ventricular Remodeling And Myocardial Autophagy In Spontaneously Hypertensive Rats And Its Possible Mechanism

Objective:To investigate the effects of different doses of berberine on ventricular remodeling and myocardial autophagy and to clarify the possible mechanism of them in spontaneously hypertensive rats(SHR).Methods:Forty 11-week-old healthy male SHR were randomly divided into 5groups:lower-dosage berberine group(BL,30mg/kg/d),medium-dosage berberine group( BM,90mg/kg/d,n=8),high-dosage berberine group( BH,270mg/kg/d),general-dosage telmisartan group(T,8mg/kg/d) and blank group(S),11-week-old healthy male Wistar-Kyoto rats as the control group(W).Each group had 8 rats.After1 week feeding,all rats were given different dosage of berberine or telmisartan(dissolved in 2ml distilled water)and isodose distilled water,1 time a day,for 24 weeks.At the end of experiment,the cardiac function and cardiac remodeling parameters were examined by Echocardiography;the myocardial interstitial collagen volume fraction was calculated by Masson staining;procollagen Ⅰ and procollagenⅢ relative m RNA expression were examind by Real time polymerase chain reaction;LC3 protein expression were examind by immunohistochemical staining; Beclin1 protein,transforming growth factor-β1 protein,phosphorylated m TOR protein,phosphorylated p38 protein, phosphorylated ERK1/2 protein expressions were analysed by Western blot.Results:Compared to S group,BL group obviously reduced in ventricular muscle fibrosis deposition(p<0.05),procollagen Ⅰ and procollagen Ⅲ relative m RNA expression levels were significantly reduced(p<0.01),the expression levels of LC3 protein and beclin1 protein and LC3 Ⅱ / LC3 Ⅰ ratio were significantly increased,and the expression levels of phosphorylated m TOR protein,phosphorylated p38 protein and phosphorylated ERK1/2 protein had different degrees of reduction,and with the increasing of berberine dosages,these changes becomed more and more obviously in BM group and BH group.Simultaneously,compared to S group,BH group left ventricular ejection fraction had significantly increased( p <0.01),and intraventricular septum in diastole had obviously reduced(p<0.05),and transforming growth factor-β1 protein expression levels had significantly reduced(p<0.01).There were not obviously differences between of above index BH group and T group,but T group had significantly reduced on systolic blood pressure.Conclusions:Autophagy is enhanced in SHR when ventricular remodeling;Berberine can promote the autophagy of SHR may be by inhibiting phosphorylated m TOR protein,phosphorylated p38 protein,phosphorylated ERK1/2 protein,and it can improve ventricular remodeling; Berberine improve myocardial fibrosis,may be related to inhibiting the expression of transforming growth factor-β1 protein.