The Effect Of Berberine Preconditioning On Norepinephrine-Induced Myocardial Injury In Rats

Objective:Our aim is to explore the effect of Berberine on norepinephrine(NE) induced myocardial injury in rats, the potential mechanism, and the dose effect relationship.Methods:In this study, the rat model of myocardial injury was created with intraperitoneal injection of norepinephrine(3mg/kg). SD rats were randomly divided into five groups, including the normal control group, the model group, the low-dose Berberine group(0.1mg/kg.d), the medium-dose Berberine group (0.2mg/kg.d), and the high-dose Berberine group(0.4mg/kg.d). Four hours after molding, all the rats were anesthetized with10%chloral hydrate(0.3ml/100g i.p.). After that, to detect the cardiac function of rats, to collect blood from the abdominal aorta, and then to take the heart with thoracotomy, all the materials were stored under favorable conditions. The following tests were performed:measurement of the serum level of cTnT with Electrochemiluminescence assay(ECLA), observation of HE stained myocardial tissue under a light microscope, measurement of the serum level of tumor necrosis factor alpha(TNF-α) by ELISA, determination of the activity of superoxide dismutase(SOD) and catalase(CAT) and the content of malondialdehyde(MDA) in the serum, measurement of the rate of cardiomyocyte apoptosis by using In situ cell death detection kit-POD, assay of the expression of Bcl-2and Bax protein in myocardial tissue by western-blotting, analysis of the Caspase-3activity in myocardial tissue by spectrophotometry, investigation of the dose-effect relationship of Berberine with Pearson Correlation Analysis.Results:Compared with the normal control group, the model group showed a series of changes listed as follows:LVSP and absolute value of±dp/dtmax decreased(P<0.01), while LVEDP increased(P<0.01); the degree of myocardial injury under a light microscope was very severe; the serum level of cTnT significantly increased (P<0.01); the activity of SOD and CAT in the serum significantly reduced(P<0.01), while the content of MDA in the serum significantly increased(P<0.01); the serum level of TNF-a significantly increased(P<0.01); the rate of cardiomyocyte apoptosis significantly increased(P<0.01); the expression of Bax protein in myocardial tissue significantly increased(P<0.01), the expression of Bcl-2protein significantly decreased(P<0.01); the activity of Caspase-3in myocardial tissue significantly increased(P<0.01).Compared with the model group, the Berberine-pretreatment groups showed a series of changes listed as follows:LVSP and absolute value of±dp/dtmax increased(P<0.01), while LVEDP decreased(P<0.01); myocardial injury had different degrees of improvement under a light microscope; the content of cTnT in the serum significantly decreased(P<0.01); the activity of SOD and CAT in the serum significantly increased (P<0.01), while the content of MDA significantly decreased(P<0.01); the serum level of TNF-α significantly reduced(P<0.01); the rate of cardiomyocyte apoptosis significantly reduced(P<0.01); the expression of Bax protein in myocardial tissue significantly reduced(P<0.01), the expression of Bcl-2protein significantly increased(P<0.01); the activity of Caspase-3significantly decreased(P<0.01).Among different Berberine-pretreatment groups, the comparison result showed that the effect of these changes produced by the increase of the dose of Berberine was gradually strengthened(P<0.01); And the dose-effect relationship of Berberine was proved by Pearson Correlation Analysis.Conclusions:Berberine pretreatment can protect NE-induced myocardial injury in a dose-dependent manner. The mechanism of this effect produced by Berberine may be related to the inhibition of myocardial apoptosis mediated by anti-oxidation and anti-inflammation.