Mechanism of AKG in regulating cardiac function and remodeling in rats through the FAK/Akt/FOXO3A signaling pathway under simulated microgravity

BUERLIENI Wulijiabieke; JULEDEZI Hailati; LI Yongshou; ZOU Yuan

doi:10.16289/j.cnki.1002-0837.2026.01012

Abstract：Objective To investigate the effects of α-ketoglutarate(AKG)on cardiac function and cardiac remodeling in rats subjected to simulated microgravity and its potential mechanisms.Methods 32 SD rats were randomly divided into the control group,AKG group,simulated microgravity group,and AKG+simulated microgravity group using a random number table,with eight rats in each group.A simulated microgravity model was established in the simulated microgravity group and the AKG+simulated microgravity group using tail suspension,and AKG was administered via drinking water(2%concentration)for 28 days.After 28 days,body weight,heart weight and soleus muscle wet weight of the rats in each group were measured,and the ratio of soleus muscle wet weight to body weight was calculated.Echocardiography was used to measure left ventricular ejection fraction(EF),left ventricular fractional shortening(FS),left ventricular internal dimension at end diastole(LVIDd),left ventricular internal dimension at end-systole(LVIDs),left ventricular anterior wall diastolic thickness(LVAWd),and left ventricular anterior wall systolic thickness(LVAWs).ELISA was used to measure adenosine triphosphate(ATP)and adenylate monophosphate(AMP)levels in myocardial tissue.HE and Masson staining were used to observe myocardial tissue morphology and degree of fibrosis.Real-time PCR was used to detect the mRNA expression of atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP).Western blot was used to detect the expression of proteins related to the focal adhesion kinase/protein kinase B/forkhead box protein O3A(FAK/Akt/FOXO3A)signaling pathway in myocardial tissue.Results Compared with the control group,the body weight,heart weight,soleus muscle wet weight,and ration of soleus muscle wet weight to body weight in the simulated microgravity group were significantly decreased(all P<0.05).EF and FS were significantly decreased,while LVIDd and LVIDs were increased,and LVAWd and LVAWs were decreased(all P<0.05).Myocardial ATP content was significantly decreased,while AMP content was significantly increased(P<0.05).Myocardial structure was disordered and collagen deposition was increased.The mRNA expressions of ANP and BNP in myocardial tissue were significantly upregulated(all P<0.05).The protein ratios of p-FAK/FAK and p-Akt/Akt and FOXO3A protein expression were significantly downregulated(all P<0.05).The protein ratios of p-FAK/FAK,p-Akt/Akt and FOXO3A protein expression in myocardial tissue of the AKG group were significantly increased compared with the control group(P<0.05),the other indicators in the AKG group showed no significant changes compared with the control group(all P>0.05).Compared with the simulated microgravity group,the AKG+simulated microgravity group showed significant improvement on the above changes.Body weight,heart weight,soleus muscle wet weight,and ratio of soleus muscle wet weight to body weight in the AKG+simulated microgravity group increased significantly(all P<0.05).In the AKG+simulated microgravity group,EF and FS increased significantly,while LVIDd and LVIDs decreased significantly,and LVAWd and LVAWs also increased significantly(P<0.05);ATP content increased significantly,while AMP content decreased significantly(P<0.05).Myocardial structure became more regular,and the area of fibrosis was significantly reduced;ANP and BNP mRNA expressions were significantly downregulated(all P<0.05).p-FAK/FAK,p-Akt/Akt protein ratios,and FOXO3A protein expression were significantly upregulated(all P<0.05).Conclusion AKG intervention can improve myocardial energy status,alleviate structural remodeling,and restore cardiac function in simulated microgravity rats,its mechanism may be related to activation of the FAK/Akt/FOXO3A signaling pathway.