山西医科大学学报2025，Vol.56Issue(11)：1219-1226,8.DOI:10.13753/j.issn.1007-6611.2025.11.003
根皮苷通过抑制NHE活性减轻AngⅡ诱导的细胞钙超载
Phlorizin alleviates AngⅡ-induced cellular calcium overload by inhibiting NHE activity
摘要
Abstract
Objective To investigate the mechanism of Phlorizin(Phl)inhibiting calcium overload.Methods Thirty male SD rats were randomly divided into five groups(n=6 per group):blank group(Ctrl group),DMSO group,model group(AngⅡ group),Phlorizin intervention group(AngⅡ+Phl group),and NHE agonist group(AngⅡ+Phl+LiCl group).Except blank group and DMSO group,the rats in the other groups received AngⅡ to induce myocardial hypertrophy and then administrated with corresponding treatments for 28 d by gavage.Cardiac structure was assessed by echocardiography,HW/BW ratio,and HE staining.The mRNA levels of atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)were measured by quantitative real-time polymerase chain reaction(qRT-PCR).The calcium content was determined by colorimetry.The recovery rate of intracellular pH in cardiomyocytes was detected by the semi-synthetic naphthofluorescein-1(SNARF-1)method.The expressions of calmodulin-dependent protein kinaseⅡ(CaMKⅡ)and its phosphorylated form(p-CaMKⅡ)were detected by Western blot.Results Compared with DMSO group,the left ventricular posterior wall thickness at end-diastole(LVWPT)was significantly increased in AngⅡ group(P<0.05),while the left ventricular end-diastolic diameter(LVDd),the left ventricular ejection fraction(LVEF),and the left ventricular fractional shortening(LVFS)were all signifi-cantly decreased(P<0.05);HW/BW was elevated(P<0.01),and myocardial fibers showed fragmentation and disorganized arrange-ment;the mRNA levels of ANP and BNP,intracellular calcium ion content,and the protein expression levels of CaMKⅡand p-CaMKⅡwere all increased(P<0.05),whereas the pH recovery rate was significantly reduced(P<0.01).Compared with AngⅡ group,LVWPT was significantly decreased in AngⅡ+Phl group(P<0.05),while LVDd,LVEF,and LVFS were significantly increased(P<0.05);HW/BW was reduced(P<0.05),and the myocardial fibers showed a relatively neat arrangement;the mRNA expression levels of ANP and BNP,intracellular calcium ion content,and the protein expression levels of CaMKⅡ and p-CaMKⅡ were all significantly de-creased(P<0.05),whereas the pH recovery rate was significantly elevated(P<0.01).Compared with AngⅡ+Phl group,LVWPT was significantly increased in AngⅡ+Phl+LiCl group(P<0.05),while LVDd,LVEF,and LVFS were significantly decreased(P<0.05);HW/BW was significantly increased(P<0.05),and the myocardial fibers showed a disorganized arrangement;the mRNA expression levels of ANP and BNP,intracellular calcium ion content,and the protein expression levels of CaMKⅡ and p-CaMKⅡ were all sig-nificantly increased(P<0.05),whereas the pH recovery rate was significantly decreased(P<0.05).Conclusion Phl could inhibit AngⅡ-induced myocardial hypertrophy in rats by suppressing NHE activity and alleviating calcium overload,and the NHE agonist LiCl can reverse this effect.关键词
根皮苷/AngⅡ/心肌肥厚/钠-氢交换/钙超载/钙调蛋白依赖性蛋白激酶ⅡKey words
Phlorizin/angiotensin Ⅱ/myocardial hypertrophy/sodium-hydrogen exchange/calcium overload/calcium/calmodulin-dependent protein kinaseⅡ分类
医药卫生引用本文复制引用
YANG Mei,LI Junhu,HAN Jianpeng,WANG Suhua,LI Xinyi..根皮苷通过抑制NHE活性减轻AngⅡ诱导的细胞钙超载[J].山西医科大学学报,2025,56(11):1219-1226,8.基金项目
山西省中医药管理局科研项目(2023ZYYC2018) （2023ZYYC2018）
