| Background: Congestive heart failure（CHF） is the final clinical manifestation of a variety ofheart diseases, including coronary heart disease, cardiomyopathy, hypertension and congenitalcardiopathy. Myocardial infarction (MI) is the most common reason. The pathophysiologicalmechanisms of HF includes hemadynamic dysfunction, neurohormonal activation and cardiacremodeling. β-adrenoceptor (β-AR) is the important member of sympathetic nervous system.It plays an important role on regulating the heart function by mediating the physiological effectof catecholamines. There are three βadrenergic receptors (β1, β2, and β3) in humancardiac myocytes which have positive inotropic response and are related to cell growth. In theearlier period of heart failure, activation of β1-adrenergic receptor can induce myocardial cellhypertrophy, apoptosis and cell necrosis and myocardial remodeling activity, stimulation of β2-adrenergic receptor is antiapoptotic and ardioprotective. β3-adrenergic receptor is seldom inhuman cardiac myocytes，which plays a role only in serious heart failure. In recent years, it hasbeen proposed that combine β1-AR blocker and β2-AR agonist treat chronic heart failure,proof shows that the effect of combined therapy on improving heart function of heart failure rat,ventricular remodeling and myocardial apoptosis is superior to β1-AR blockers alone.Exposure to particulate matter which diameter less than or equal to2.5μm (PM2.5) has beenimplicated as a risk factor on respiratory system and cardiovascular system. Especially,exposure to PM2.5has been linked to ischemic heart disease. Numerous studies confirmedlong-term and short-term PM exposures may play a role in triggering acute ischemic heartdisease events. The possible mechanisms include activation of the sympathetic nervous system,oxidative stress, inflammation, atherosclerosis, destruction of blood coagulation, and thus affectthe cardiovascular system, for example, ischemic stroke, ECG ST-segment depression,increased plasma viscosity, increased circulating markers of inflammation, and changes in heart rate variability.However, the studies about the effect of β adrenergic receptor subtypes on cardiac function inmyocardial infarction rats which were treated by PM2.5have not been reported. In our study,we have recognized the effect of metoprolol (β1-AR blockers) and terbutaline (β2-ARagonist) on cardiac function in myocardial infarction rats which were treated by PM2.5.Objective：To investigate whether the effect of combined β1adrenergic receptor blocker and β2adrenergic receptor agonist on improving heart function of heart failure rat, ventricularremodeling and myocardial apoptosis is superior to β1AR blockers alone, and to observe theeffect of metoprolol and terbutaline on cardiac function in myocardial infarction rats whichwere treated by PM2.5.Methods: Models of congestive heart failure （CHF） were established by left anteriordescending coronary artery（LAD） ligature. Thirty SD rats were randomly divided into fivegroups (n=6in each): sham（control）, MI, metoprolol (20mg/kg,2/d), terbutaline (2mg/kg,2/d),metoprolol (20mg/kg,2/d) plus terbutaline (2mg/kg,2/d). Which were administeredrespectively to three groups by gavage after1week in surgery. Cardiac function was examinedby echocardiographic and hemodynamic measurements after8week; protein levels weremeasured by Western blotting; myocardial GSH measurement using a GSH reductase-coupledenzymatic assay. The other fifty rats were divided into five groups (n=10in each) the same asbefore, All rats were exposure to PM2.5after8week. Survival rates in each group wereanalyzed.Results:(1)Compared with the control group, both LVEDD and LVESD increased inmyocardial infarction rats, with LVEDD from （5.79±0.32）to（8.88±0.41）mm, and LVESDfrom（2.56±0.32）to（7.13±0.26）mm. Moreover, the left ventricular FS and EF of myocardialinfarction rats were significantly decresed in myocardial infarction group.It was showed that EFdecreases from（75.1±4.12）%in control group to (33.4±3.19)%in MI group（P＜0.05）, andFS decreases from （45.3±2.03）%to（17.4±2.70）%（P＜0.05）. Compared with the MI group,LVEDD and LVESD decreased（P＜0.05），and EF、FS in left ventricular increase （P＜0.05）after treatments with metoprolol or terbutaline alone or metoprolol plus terbutaline inadministration groups. Especially, the effect of metoprolol plus terbutaline is better than metoprolol alone or terbutaline alone.(2) MI rats exhibited a marked decrease in LVSP, LVEDP, as well as impairment in±dP/dt.After treatments of metoprolol, terbutaline, or metoprolol plus terbutaline, LVSP, as well as±dP/dt increasedand LVEDP decreased significantly. The results showed that LVSPincreasedfrom（62.19±7.36）to（91.76±6.51）,（92.33±7.16）and（119.52±6.06）mmHg, respectively,+dp/dt increased from（1462±126）to（2376±102）,（2262±105）,（2883±118）mmHg/s,respectively, and-dp/dt increased from（1476±128）to（2720±106）（,2282±112）and（2932±122）(mmHg/s),respectively. Additionally, LEVDP decreased from（4.90±0.81）to（1.83±0.30）,（2.86±0.69）and（1.22±0.28）mmHg/s, respectively（P＜0.05）。It was also showed that thetherapeutic effect of metoprolol plus terbutaline is better than metoprolol alone or terbutalinealone.(3) Bcl-2protein expression was decreased in the CHF animals. This was associated with anincrease in Bax protein. The effect of metoprolol plus terbutaline is significantly stronger thanmetoprolol alone or terbutaline alone.(4) As showed by TUNNEL detection, cardiomyocyte apoptosis in MI group is more evidentthan in control group, which was partly inbibited when treated with metoprolol or terbutalinealone or combined. The effect of metoprolol plus terbutaline is significantly stronger thanmetoprolol or terbutaline alone.(5) Left ventricular GSH/GSSG was decreased in CHF animals. Drug interventions attenuatedthe decrease of tissue GSH/GSSG. The changes were most marked in the metoprolol plusterbutaline-treated CHF animals.(6) Forty-eight hours after exposure to PM2.5. There were significant differences between MIgroup and the other groups, and no significant differences between sham group andadministration groups.Conclusions: The β1adrenergic receptor blocker and β2adrenergic receptor agonist may beimportant clinical therapy approach in the treatment of CHF. Especially, combine β1adrenergic receptor blocker with β2adrenergic receptor agonist has a better efficacy.Short-term exposure to PM2.5contributes to aggravate cardiac function in myocardial infarction rats. The β1adrenergic receptor blocker and β2adrenergic receptor agonist maydecrease the mortality rate after exposure to PM2.5. |
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