5α-还原酶抑制剂减轻肥胖雄性大鼠心脏氧化应激损伤的机制研究OA

Objective To investigate the mechanism by which the 5α-reductase inhibitor finas-teride alleviates cardiac oxidative stress injury in obese male rats,and to provide evidence for its ap-plication in the prevention and treatment of obesity-related heart diseases.Methods Forty-eight clean-grade healthy male Sprague-Dawley rats were randomly divided into normal group,model group,normal+inhibitor group,and model+inhibitor group,with 12 rats in each group.Obesity was induced in the model group and the model+inhibitor group,while the other groups were fed a normal diet.After modeling,rats in the normal group and the model group were intragastrically adminis-tered an equal volume of 0.9％sodium chloride injection,and rats in the normal+inhibitor group and the model+inhibitor group were intragastrically administered finasteride 5 mg/kg once daily for 6 consecutive weeks.Body weight and visceral fat mass were recorded.Blood glucose,insulin,ho-meostatic model assessment of insulin resistance(HOMA-IR),cholesterol,triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),non-high-density lipoprotein cholesterol(non-HDL-C),dihydrotestosterone(DHT),malondialdehyde(MDA),and reactive oxygen species(ROS)levels were measured.Left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were assessed by echocardiography.The protein expression levels of peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α),4-hydroxynonenal(4-HNE),glutathione peroxidase 4(GPX4),interleukin-6(IL-6),and andro-gen receptor(AR)in cardiac tissue were detected.Results Compared with the normal group and the normal+inhibitor group,body weight and visceral fat mass were significantly increased in the model group and the model+inhibitor group(P＜0.05).Compared with the normal group,serum TG levels were significantly increased in the normal+inhibitor group,and insulin,HOMA-IR,and total cholesterol levels were significantly increased in the normal+inhibitor group,the model group,and the model+inhibitor group(P＜0.05).Compared with the normal+inhibitor group,TG levels were significantly decreased,and cholesterol,LDL-C,and non-HDL-C levels were significantly in-creased in the model group and the model+inhibitor group(P＜0.05).Compared with the normal group,LVEF and LVFS were significantly decreased in the model group(P＜0.05);compared with the model group,LVEF and LVFS were significantly increased in the model+inhibitor group(P＜0.05).Compared with the normal group,serum DHT levels were significantly decreased,and MDA and ROS levels were significantly increased in the normal+inhibitor group(P＜0.05).Com-pared with the normal+inhibitor group,DHT,MDA,and ROS levels were significantly increased in the model group(P＜0.05).Serum DHT and MDA levels were significantly lower in the model+inhibitor group than those in the model group(P＜0.05).There were no statistically significant differences in PGC-1α,IL-6,and AR protein expression levels among the groups(P＞0.05).Compared with the normal group,4-HNE protein expression was significantly increased in the model group,and GPX4 protein expression was significantly increased in the normal+inhibitor group and the model+inhibitor group(P＜0.05).Compared with the model group,4-HNE protein expression was significantly decreased,and GPX4 protein expression was significantly increased in the model+inhibitor group(P＜0.05).Conclusion 5α-reductase inhibitor finasteride alleviates myocardial lipid peroxidation injury and improves left ventricular systolic function in high-fat diet-induced obese rats by inhibiting DHT synthesis,upregulating GPX4,and downregulating 4-HNE,providing a no-vel interventional target for obesity-related cardiovascular diseases.