Betaine Protects Against Acute Myocardial Ischemic Injury Through Regulation Of RhoA/ROCK Pathway In Rats

Objective The present study was designed to investigate the cardioprotective effect of betaine on regulation of ODC/SSAT protein expression and Rho A/ROCK pathway.Methods Male Sprague-Dawley rats were divided into six groups: Control group, ISO group, betaine(100, 200 and 400 mg·kg-1) +ISO groups and betaine(400 mg·kg-1) alone group. Betaine(100 mg·kg-1, 200 mg·kg-1 and 400 mg·kg-1) were administered orally once a day for 40 days, and acute myocardial injury was induced by subcutaneous injection of isoproterenol(85 mg·kg-1·d-1) in rats on the 38 th and 40 th day. Myocardial injury was examined by histopathological evaluation, myocardial tissue levels of collagen typeⅠ(COLⅠ), collagen type Ⅲ(COLⅢ), COLⅠ/ COL Ⅲ, angiotension converting enzyme(ACE), AngiotensinⅡ(ANGⅡ), insulin-like growth factor 1(IGF-1), and serum levels of transforming growth factor β1(TGF-β1), endothelin 1(ET-1) were detected. The protein expression of ODC, SSAT, Rho A, ROCK1, ROCK2, e-NOS were measured by Western blot.Key findings Oral administration of betaine significantly attenuated myocardial necrosis, interstitial edema, and inflammatory cell infiltration. Betaine(200, 400mg·kg-1) reduced myocardial tissue levels of COLⅠ, COLⅢ, COLⅠ/COLⅢ, ACE, ANGⅡ, and myocardial tissue levels of IGF-1 was further increased by betaine(400mg·kg-1)(P<0.01). Betaine(100,200 and 400 mg·kg-1) treatment decreased serum levels of TGF-β1, ET-1(P<0.01). Western blot analysis showed that protein expression of Rho A, ROCK1 and ROCK2 in isoproterenol induced myocardium were markedly decreased by Betaine(100, 200 and 400 mg·kg-1) pretreatment(P<0.01). e-NOS and ODC expression were normalized and SSAT was further enhanced by Betaine(200,400 mg·kg-1)(P<0.05). And betaine(400 mg·kg-1) alone had no effect on normal myocardial tissues.Conclusions The present study have demonstrated that betaine protects against isoproterenol-induced myocardial ischemia via modulation of ODC/SSAT expression and regulation of Rho A/ROCK pathway.