中国比较医学杂志2025，Vol.35Issue(8)：29-38,10.DOI:10.3969/j.issn.1671-7856.2025.08.003
新型磷酸二酯酶5抑制剂CPD1促进自噬激活对病理性心肌肥大大鼠心脏的保护作用
Protective effect of novel phosphodiesterase 5 inhibitor CPD1 on promoting autophagy activation in hearts of rats with pathological myocardial hypertrophy
摘要
Abstract
Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180～200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P＜0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P＜0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.关键词
CPD1/病理性心肌肥大/自噬/腹主动脉缩窄/左心功能/西地那非Key words
CPD1/pathological cardiac hypertrophy/autophagy/abdominal aorta constriction/left heart function/sildenafil分类
医药卫生引用本文复制引用
张雪娣,崔华穗,宋业鼎,陈昊妍,崔锡平,李芳红,穆云萍,赵子建..新型磷酸二酯酶5抑制剂CPD1促进自噬激活对病理性心肌肥大大鼠心脏的保护作用[J].中国比较医学杂志,2025,35(8):29-38,10.基金项目
国家自然科学基金青年项目(82100064) （82100064）
广州市科技计划项目(2023B03J1291) （2023B03J1291）
"癌症、心脑血管、呼吸和代谢性疾病防治研究"国家科技重大专项(2023ZD0506900). （2023ZD0506900）
