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彭丽琪, 欧长莹, 王贤颖, 陈梦婷, 魏子涵, 陈新宇, 唐燕萍.基于Wnt/β-catenin信号通路探讨温阳振衰颗粒对慢性心力衰竭大鼠心室重构的影响[J].湖南中医药大学学报,2026,46(1):7-13[点击复制] |
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| 基于Wnt/β-catenin信号通路探讨温阳振衰颗粒对慢性心力衰竭大鼠心室重构的影响 |
| 彭丽琪,欧长莹,王贤颖,陈梦婷,魏子涵,陈新宇,唐燕萍 |
| (湖南中医药大学, 湖南 长沙 410208;湖南中医药大学中西医结合学院, 湖南 长沙 410208;湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 基于调控无翅型MMTV整合位点家族(Wnt)/β-catenin信号通路探讨温阳振衰颗粒(WZG)对慢性心力衰竭(CHF)大鼠心室重构的影响。方法 采用腹腔注射阿霉素(DOX)建立CHF大鼠模型。造模成功后,将大鼠随机分为模型组(CHF组)、WZG低剂量组(WZG-L组,0.72 g/kg)、WZG中剂量组(WZG-M组,1.44 g/kg)、WZG高剂量组(WZG-H组,2.88 g/kg)、依那普利组(ENP组,1.8 mg/kg),每组10只;另取10只为正常对照组(NC组)。NC组与CHF组给予等体积蒸馏水,其余各组按剂量灌胃相应药物,均连续干预4周。超声心动图检测心功能;ELISA测定血清N末端脑利钠肽前体(NT-proBNP)水平;测算左心室重量指数(LVMI)评估心室重构;Masson染色观察心肌组织病理及胶原容积分数(CVF);Western blot检测心肌组织中蓬乱蛋白1(DVL1)及β-catenin蛋白的表达。结果 与NC组比较,CHF组大鼠左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)及LVMI升高(P<0.05,P<0.01),射血分数(EF)及左心室缩短分数(FS)降低(P<0.01),心肌纤维排列紊乱,CVF增加(P<0.01),血清NT-proBNP水平升高(P<0.01),心肌组织中DVL1、β-catenin表达上调(P<0.01)。与CHF组比较,WZG-L组、WZG-M组、WZG-H组LVIDd、LVIDs、LVMI降低(P<0.01),EF、FS提高(P<0.01),心肌病理损伤改善,CVF降低(P<0.05,P<0.01),血清NT-proBNP水平下调(P<0.01),心肌组织中DVL1、β-catenin的表达下调(P<0.05)。结论 WZG可有效改善DOX诱导的CHF大鼠心肌损伤,减轻心肌纤维化,抑制心室重构,其作用机制可能与抑制Wnt/β-catenin信号通路中关键蛋白的异常表达有关。 |
| 关键词: 慢性心力衰竭 温阳振衰颗粒 心肌纤维化 心室重构 Wnt/β-catenin信号通路 |
| DOI:10.3969/j.issn.1674-070X.2026.01.002 |
| 投稿时间:2025-08-15 |
| 基金项目:湖南省自然科学基金高校联合基金项目(2025JJ90051);湖南省中医药科研课题(B2023026);湖南省卫生健康委员会科研计划项目(202203015711);国家级大学生创新训练计划项目(S202410541043);湖南省大学生创新创业训练计划项目(2024-2864);湖南中医药大学本科生科研创新基金项目(2023BKS036,2024BKS139);湖南省研究生科研创新项目(CX20230806)。 |
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| Effects of Wenyang Zhenshuai Granules on ventricular remodeling in rats with chronic heart failure via the Wnt/β-catenin signaling pathway |
| PENG Liqi, OU Changying, WANG Xianying, CHEN Mengting, WEI Zihan, CHEN Xinyu, TANG Yanping |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To explore the effects of Wenyang Zhenshuai Granules (WZG) on ventricular remodeling in rats with chronic heart failure (CHF) based on the regulation of Wnt/β-catenin signaling pathway. Methods A CHF rat model was established via intraperitoneal injection of doxorubicin (DOX). After successful modeling, rats were randomly assigned to model group (CHF group), WZG low-dose group (WZG-L group, 0.72 g/kg), WZG medium-dose group (WZG-M group, 1.44 g/kg), WZG high-dose group (WZG-H group, 2.88 g/kg), and enalapril group (ENP group, 1.8 mg/kg), with ten rats per group. An additional ten rats served as normal control group (NC group). The NC and CHF groups received equal volumes of distilled water, while the remaining groups received corresponding drugs by gastric gavage at their respective doses for four consecutive weeks. Echocardiography was used to evaluate cardiac function. Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured by ELISA. Left ventricular mass index (LVMI) was calculated to evaluate ventricular remodeling. Myocardial tissue pathology and collagen volume fraction (CVF) were examined using Masson's trichrome staining. Western blot was performed to determine the Dishevelled-1 (DVL1) and β-catenin protein expressions in myocardial tissues. Results Compared with the NC group, rats in the CHF group exhibited increased left ventricular internal diameter at end-diastole (LVIDd), left ventricular internal diameter at end-systole (LVIDs), and LVMI (P<0.05, P<0.01), decreased ejection fraction (EF), and left ventricular shortening fraction (FS) (P<0.01), disorganized myocardial fiber arrangement, increased CVF (P<0.01), higher serum NT-proBNP levels (P<0.01), and up-regulated expressions of DVL1 and β-catenin in the myocardial tissues (P<0.01). Compared with the CHF group, the WZG-L, WZG-M, and WZG-H groups exhibited reduced LVIDd, LVIDs, and LVMI (P<0.01), increased EF and FS (P<0.01), alleviated myocardial pathological injury with decreased CVF (P<0.05, P<0.01), lower serum NT-proBNP levels (P<0.01), and downregulated DVL1 and β-catenin expressions in the myocardial tissues (P<0.05). Conclusion WZG can effectively ameliorate myocardial injury in rats with DOX-induced CHF, mitigate myocardial fibrosis, and inhibit ventricular remodeling. Its mechanism of action may be associated with the suppression of the abnormal expression of key proteins in the Wnt/β-catenin signaling pathway. |
| Key words: chronic heart failure Wenyang Zhenshuai Granules myocardial fibrosis ventricular remodeling Wnt/β-catenin signaling pathway |
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