摘要
目的 探讨益气温阳逐水方通过调控水通道蛋白和心肌能量代谢改善心力衰竭的作用及机制。方法 将50只SD大鼠随机分为5组:假手术组,模型组,益气温阳逐水方低、中、高剂量组分别给予0.12、0.27、0.56 g/kg益气温阳逐水方灌胃;假手术组给予等量蒸馏水灌胃。连续灌胃4周后进行心功能检测,小动物超声观察大鼠心脏左室射血分数(left ventricular ejection fraction, LVEF)、左室收缩分数(left ventricular systolic fraction, LVFS)、舒张末期左室内径(left ventricular end diastolic diameter, LVIDd)、收缩末期左室内径(left ventricular end systolic diameter, LVIDs)水平变化。取材后进行各组大鼠心脏组织形态学变化检测,HE染色法检测各组大鼠心脏大小及病理学变化;采用Masson染色法观察各组大鼠心脏组织纤维蛋白沉积情况;酶联免疫吸附试验(enzyme-linked immunosorbent assays, ELISA)法检测能量代谢三磷酸腺苷(adenosine triphosphate, ATP)、二磷酸腺苷(adenosine-diphosphate, ADP)、单磷酸腺苷(adenosine monophosphate, AMP)相关指标变化;实时荧光定量聚合酶链反应(quantitative real-time PCR,RT-qPCR)法检测水通道蛋白及能量代谢相关基因水平变化,主要包括水通道蛋白1(aquaporin 1,AQP1)、水通道蛋白4(aquaporin 4,AQP4)、水通道蛋白7(aquaporin 7,AQP7)、心房肽(atrial natriuretic peptide, ANP)、脑型利钠肽(brain-type natriuretic peptide, BNP)、腺苷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)、过氧化物酶体增殖剂激活α(peroxisome proliferator-activated receptor α,PPARα)、过氧化物酶体增殖物激活受体γ共激活因子-1α(peroxisome proliferator-activated receptor-γ coactivator-1α,PGC-1α)。结果 与假手术组比较,模型组大鼠的LVEF、LVFS水平显著降低(P<0.01),心肌纤维化面积显著增加(P<0.01),血管周围及间质的胶原纤维沉积显著增加(P<0.01),ATP含量显著降低(P<0.01),ADP和AMP含量上升(P<0.05),AQP1、AQP4、AQP7、ANP、 BNP mRNA表达水平显著升高(P<0.01),AMPK、PPARα、PGC-1α mRNA表达水平显著降低(P<0.01)。与模型组比较,益气温阳逐水方高剂量组的上述各项检测指标均得到明显改善(P<0.01)。结论 益气温阳逐水方能够改善大鼠心力衰竭状态,其机制可能与调控水通道蛋白和心肌能量代谢相关。
Objective To investigate the effect and mechanism of Yiqi Wenyang Zhushui Decoction(益气温阳逐水方)on im-proving heart failure by regulating aquaporin(AQP)and myocardial energy metabolism.s Methods Fifty SD rats were randomly di-vided into 5 groups:sham operation group,model group,Yiqi Wenyang Zhushui Decoction low-dose,medium-dose and high-dose groups(0.12,0.27 and 0.56 g/kg,intragastric administration).The sham operation group was given the same amount of distilled water by intragastric administration.After 4 weeks of continuous intragastric administration,the cardiac function was test-ed.The changes of left ventricular ejection fraction(LVEF),left ventricular systolic fraction(LVFS),left ventricular end diastolic diameter(LVIDd)and left ventricular end systolic diameter(LVIDs)were observed by ultrasound in small animals.The heart histomorphological changes of rats in each group were detected,and the heart size and pathological changes of rats in each group were detected by HE staining.Masson staining was used to observe the fibrin deposition in heart tissues of rats in each group.The changes of related indexes of energy metabolism adenosine triphosphate(ATP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)were detected by ELISA.The changes of AQP and related genes of energy metabolism were detected by RT-QPCR,including AQP1,AQP4,AQP7,atrial natriuretic peptide(ANP),B-type diuretic natriuretic peptide(BNP),AMP-activated protein kinase(AMPK),peroxide proliferation activated receptorα(PPARα)and peroxisome proliferator activated receptorγcoactivator 1α(PGC-1α).s Results Compared with those of the sham operation group,the levels of LVEF and LVFS in the model group were significantly decreased(P<0.01),the area of myocardial fibrosis was significantly increased(P<0.01),the collagen fiber deposition in perivascular and interstitium was significantly increased(P<0.01),the ATP content was signifi-cantly decreased(P<0.01),the contents of ADP and AMP were increased(P<0.05),the mRNA expression levels of AQP1,AQP4,AQP7,ANP and BNP were significantly increased(P<0.01),and the mRNA expression levels of AMPK,PPARαand PGC-1αwere significantly decreased(P<0.01).Compared with those of the model group,the above indexes of Yiqi Wenyang Zhushui Decoction high-dose group were significantly improved(P<0.01).n Conclusion Yiqi Wenyang Zhushui Decoction can improve the state of heart failure in rats,and its mechanism may be related to the regulation of aquaporin and myocardial energy metabolism.
作者
陈翊
林凯旋
李雪山
韩永继
黄国强
李建功
CHEN Yi;LIN Kaixuan;LI Xueshan;HAN Yongji;HUANG Guoqiang;LI Jiangong(Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine,Zhongshan 528400,Guangdong,China)
出处
《中华中医药学刊》
CAS
北大核心
2023年第10期48-52,I0009,I0010,共7页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金项目(81804048)
广东省中医药局科研项目(20221428)。
关键词
心力衰竭
益气温阳逐水法
水通道蛋白
能量代谢
heart failure
Yiqi Wenyang Zhushui Decoction(益气温阳逐水方)
aquaporin
energy metabolism
作者简介
陈翊(1980-),男,广东湛江人,副主任中医师,硕士,研究方向:中医药防治心血管疾病。
