| Objectives The present study was designed to investigate the cardioprotective effectsand mechanism of betaine on isoproterenol-induced acute myocardial ischemia in rats.Methods Sprague-Dawley rats (120in total) were divided into six groups: Controlgroup, ISO group, betaine (100,200and400mg·kg-1)+ISO groups and only betaine (400mg·kg-1). Rats were pretreated with betaine (100,200and400mg·kg-1) orally for40days.Acute myocardial ischemic injury was induced in rats by subcutaneous injection ofisoproterenol (85mg·kg-1), for two consecutive days.The serum levels of cardiac troponin I(cTn I), interleukin-6(IL-6), vascuolar cell adhesion molecule1(VCAM-1) were measured.Pathological changes in the morphological structure of myocardial tissue were evaluated byhematoxylin-eosin staining. Western-blot was used to analyze STAT3, phospho-STAT3(Tyr705), JAK2, phospho-JAK2(Y1007+Y1008), Bcl-2and Bax protein levels. In addition,biochemical enzymes and lipid profile were measured.Key findings Oral administration of betaine (200and400mg·kg-1) significantlyreduced the level of cardiac marker enzyme in the serum and ameliorated the histologicaldamage of the hearts induced by isoproterenol. Western blot analysis showed that betaine(400mg·kg-1) treatment maintained or further enhanced phosphorylation of STAT3(Tyr705)and JAK2in isoproterenol-induced myocardium, but had no effect on the expression ofSTAT3and phospho-JAK2(Y1007+Y1008) protein among all groups. And oraladministration of betaine (400mg·kg-1) could significantly increase the expression of Bcl-2protein, betaine (200and400mg·kg-1) decrease the expression of Bax protein in impairedventricular which resulted elevating the decrease of Bcl-2/Bax ratio caused by isoproterenol treatment (P<0.05). Meanwile, betaine treatment could significantly reduce the increase ofIL-6and VCAM-1in isoproterenol-induced acute myocardial ischemia (P<0.05). Comparedwith the control group, the content of AST, ALT and LDL were significantly increased andTG was decreased in ISO group, but betaine treatment groups had no effect on biochemicalenzymes and lipid profile (P>0.05). And betaine (400mg·kg-1) alone had no effect on nomalmyocardial tissues.Conclusions Our results suggested that betaine pretreatment can attenuateisoproterenol-induced acute myocardial ischemia via the regulation of STAT3and Bcl-2/Baxexpression and reduction of the content of IL-6and VCAM-1. |
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