Mechanism Of Sodium-glucose Cotransporter 1(SGLT-1)in Cardiac Hypertrophy

Objective:To investigate the relationship of sodium-glucose cotransporter 1(SGLT-1)and cardiac hypertrophy under different conditions.And explore the mechanism.Methods:Part 1:From September 2017 to April 2019,patients who underwent modified Morrow operation due to hypertrophic obstructive cardiomyopathy in affiliated cardiovascular hospital of Kunming medical university/Fuwai cardiovascular hospital of Yunnan province were collected as experimental group.Meanwhile,patients undergoing mitral valve replacement due to rheumatic valvular disease were selected as the control group.35 patients in the experimental group and 35 patients in the control group were stained with HE to observe the morphology of cardiomyocytes under microscope,and the expression of SGLT-1 was detected by Western Blot and compared between the two groups.Part 2:Two different mouse models of cardiac hypertrophy were constructed.Model 1:cardiac hypertrophy model induced by increased afterload,hypertension induced by high sodium diet.Model 2:drug cardiac hypertrophy model,pirarubicin was injected into the tail vein to induce cardiac hypertrophy.Control groups were set up for the two models.After the successful establishment of the model,blood pressure,cardiac function and other indicators were measured,then the left ventricular tissues were taken and weighed,and the expression levels of SGLT-1,AKT,p-AKT,mTOR,p-mTOR,P70S6K1 and p-P70S6K1 in the tissues were determined by Western blot.Part 3:Two models of rat cardiomyocytes H9c2 were constructed.Model 1:angiotensin Ⅱ induction.Experimental group 1:culture medium+Ang Ⅱ(1mmol/L)for 72 hours;Experimental group 2:culture medium+Ang Ⅱ(10mmol/L)for 72 hours;Experimental group 3:culture medium +Ang Ⅱ(100mmol/L)for 72 hours;Blank control group:ordinary medium culture for 72 hours.Model 2:pirorubicin induction.Experimental group:piropiacin was treated with 5 mol/L for 24 hours.Control group:ordinary medium culture for 24 hours.Cell activity was measured by MTT assay.Cell morphology and diameter were measured under microscope.SGLT-1,AKT,p-AKT,mTOR,p-mTOR,P70S6K1 and p-P70S6K1 were determined by Western Blot.The expression of apoptotic factors Bax,Bcl-2,caspase-3 and caspase-9 in model 2 was detected by q-PCR.Results:1.SGLT-1 in the ventricular septal tissues of patients with hypertrophic cardiomyopathy were higher than control group(mitral papillary muscle tissues of patients with rheumatic mitral valve disease)(P<0.05).2.The protein content of SGLT-1 in the myocardial tissue of hypertensive mice induced by high-sodium diet was higher than the control group and the ratios of p-AKT/AKT,p-mTOR/mTOR and p-P70S6K1/P70S6K1 were higher.(P<0.05).3.After pirubicin treatment,the left ventricular tissue quality increased,the expression of SGLT-1 in myocardial tissue decreased,and the ratios of p-AKT/AKT,p-mTOR/mTOR,and p-P70S6K1/P70S6K1 were decreased.(P<0.05).4.Angiotensin Ⅱ can induce hypertrophy of H9c2 cells,increase the expression of SGLT-1 in cells,and increase the ratios of p-AKT/AKT,p-mTOR/mTOR,and p-P70S6K1/P70S6K1.(P<0.05).5.After the treatment of H9c2 cells with irirubicin,cell diameter decreased,Bcl-2 gene was down-regulated,and Bax,caspase-3 and caspase-9 genes were up-regulated(P<0.05).Conclusion(s):1.In patients with hypertrophic cardiomyopathy,SGLT-1 expression was increased in hypertrophic myocardial tissue.2.SGLT-1 may be involved in the process of cardiac hypertrophy in hypertensive heart disease by activating the PI3K/AKT/mTOR signaling pathway.3.SGLT-1 may participate in angiotensin-Ⅱ-induced H9c2 cell hypertrophy by activating the PI3K/AKT/mTOR signaling pathway.4.Pirubicin can increase the weight of the heart in the body,but it does not cause hypertrophy of cardiomyocytes,and can induce apoptosis of cardiomyocytes.SGLT-1 expression and PI3K/AKT/mTOR signaling pathway are inhibited.5.The SGLT-1 and PI3K/AKT/mTOR pathways are involved in cardiac hypertrophy caused by various pathological conditions.In the future,inhibition of SGLT-1 expression by drugs or other means or blocking of PI3K/AKT/mTOR pathways may effectively control pathological cardiac hypertrophy,which is expected to be a new target for the treatment of cardiac hypertrophy.