Preventive Effects Of Betaine On Isoproterenol-induced Acute Myocardial Ischemic Rats Via Regulation Of Nitric Oxide Synthase And GSK-3Signaling Pathway

Objectives Our study was designed to investigate the protective effect of betaine onisoproterenol-induced acute myocardial ischemic rats via nitric oxide synthase (eNOS, iNOS)and glycogen synthase kinase-3α/β(GSK-3α/β) signaling pathway in cadiocyte.Methods Male Sprague-Dawley rats(40in total) were pretreated with oraladministration of betaine(100,200and400mg/kg per day) for40days. And acute myocardialischemic injury was established in rats by two days subcutaneous injection withisoproterenol(85mg/kg). Hemodynamic and biochemical parameters, histopathologicalvariables, and the protein expression of eNOS/p-eNOS(Ser1177), iNOS, PI3K(p110γ)Akt/p-Akt(Ser473), GSK-3α/p-GSK-3α(Ser21) and GSK-3β/p-GSK-3β(Ser9) in myocardialtissue were analysed.Results Oral administration of betaine groups (100,200and400mg/kg per day for40days of each group) reduced the injury of the isoproterenol-induced acute myocardialischemia, decreased the cardiac troponin I(cTnI) in plasma, improved the dysfunction of leftventricular (LV) including increased left ventricular systolic pressure (LVSP) and maximumrate of developed left ventricular pressure (LV dP/dtmax), and decreased the minimum rate ofdeveloped left ventricular pressure (LV dP/dtmin). Histopathological study showed that thepretreated use of betaine (100,200and400mg/kg) attenuated myonecrosis and leukocyticcells infiltration, and prevented isoproterenol-induced myocardiolysis. There were nosignificant changes in heart rate and mean arterial pressure(MAP) in each experimental group (all P>0.05). In isoproterenol-treated group, the expression of eNOS/phospho-eNOSAkt/phospho-Akt, phospho-GSK3α and phospho-GSK3β were lower than those in normalrats (P<0·05), and GSK3β increased(P<0·05) in modal group. Betaine （100、200and400mg/kg）treatment has increased the protein content of Akt、p-Akt(Ser473), eNOS,p-eNOS(Ser1177), p-GSK-3α(Ser21) and p-GSK-3β(Ser9), meanwhile reduced theexpression of GSK-3β. However, no apparent changes were observed in expression of PI3Kand GSK3α among all the groups (all P﹥0.05). The protein iNOS was not appear in controlgroup, but all expressed in modal group, and had a two over eight expression in betaine100mg/kg group.Conclusions Our results show that betaine protects against isoproterenol-inducedmyocardial ischemia via NOS and GSK-3α/β signal pathway.