| Objective: Over-excited sympathetic nerve system and elevated plasma catecholamine will harm the circulation system. Lots of clinical trials have proved that β blockade would alleviate the symptoms of patients with heart failure and decrease the mortality of heart failure obviously, but the mechanism remains unclear. In our study, we established ischemic heart model of rats by subcutaneous injection of isoproterenol(ISO), the ventricular weight to body weight ratio and the concentration of collagen in ventricle were detected, myocardiac necrosis(HE stainning) and fibrosis(Masson stainning) were observed , expressions of apoptosis related gene Fas and Bcl-2 were detected by immunohistochemistry. Bisoprolol was used to prevent the heart from injury induced by ISO. Through this study, we want to verify the mechanism of how the β blockade can benefit on the injured heart induced by ISO.Methods: Subcutaneous infusion of ISO established the ischemic model of myocardium in rats. 52 Wistar(WS) rats were randomly divided into 3 groups: (l)placebo group(n=12): each rat was injected normal saline 1 ml/day (10 days) throughsubcutaneous way. (2) ISO group (n=20): ISO was injected through subcutaneous way, the dosage was 1 mg/Kg/day(10 days); (3) bisoprolol group(n=20): bisoprolol (2mg/Kg/day) had been fed for 3 days, then ISO(1 mg/kg/day) was injected daily(for10 days) through subcutaneous way ;at the same time , bisoprolol(2 mg/kg/day) was fed also. On the 15th day, all the rats were killed. The ventricular weight to body weight ratio, and the concentration of collagen in the ventricle were detected; the morphological changes of the heart (necrosis with HE stainning, fibrosis with Masson staining) were observed; the products of apoptosis related gene Fas and Bcl-2 were detected by SP immunohistochemical stainning. The statistical data was analyzed by ANOVA, Chi-square test. Value of P<0.05 was considered to be significant.Results1. The effects of bisoprolol on ventricular weight to body weight ratio and the concentration of collagen in ventricle induced by ISO: in ISO group, the ventricular weight to body weight ratio (mg/g) was 6.28±1.10, the concentration of collagen in ventricle was 8.717 ± 0.795 ng/mg, all of them raised obviously comparing with placebo(p<0.05). The ventricular weight to body weight in bisoprolol group (mg/g) was 5.53 ± 0.87, the concentration of collagen was 7.897 ± 0.107ng/mg, they decreased obviously comparing with ISO group (p<0.05).2. The effects of bisoprolol on necrosis induced by ISO: in ISO group, the necrotic foci of myocardium was obvious under microscope (HE stainning, Rona classification, 1 grade 2 rats, 2 grade 10 rats, 3 grade 5 rats, 4 grade 3 rats); in bisoprolol group, the necrotic foci was alleviated comparing with ISO group (Rona Classification, 1 grade11 rats, 2 grade 7rats, 3 grade 2 rats, 4 grade 0 rat, p<0.05).3. The effects of bisoprolol on expressions of apoptosis related genes: in ISO group, PI of Fas was 21.47 ± 8.10% , PI of Bcl-2 was 19.36 ± 5.76%, they increased obviously comparing with placebo (p<0.01); in bisoprolol group, PI of Fas was 16.31±5.12%, was lower than ISO group (p<0.05), PI of Bcl-2 was 24.05 ± 6.65%, was higher thanISO group (p<0.05).Conclusion: large dose infusion of ISO can cause necrosis of myocardium, myocardiac fibrosis and over-expression of Fas and Bcl-2 in rats ;expression of Fas and Bcl-2 mainly located around the necrotic foci, bisoprolol can effectively decrease the necrotic area, inhibite fibrosis of myocardium and expression of Fas, elevate expression of Bcl-2.
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