二氢杨梅素改善ob/ob小鼠心脏功能及其相关作用机制研究

目的 探讨二氢杨梅素(dihydromyricetin,DHM)对瘦素(leptin)突变型ob/ob肥胖小鼠心脏功能的保护作用及其相关分子机制.方法 36只雄性ob/ob小鼠采用随机数字表法分为ob/ob组、DHM 50 mg/kg干预组(ob/ob+ DHM 50 mg/kg)、DHM 100 mg/kg干预组(ob/ob+ DHM 100 mg/kg),每组12只,干预16周;10只C57 BL/6J野生型小鼠作为正常对照组(WT).检测葡萄糖耐量和胰岛素耐量,超声心动图检测心脏功能;HE和Masson染色检测心肌的组织形态和胶原沉积;Western blot检测心肌组织中过氧化物酶体增殖活化受体γ共激活因子-1α (peroxisome proliferator activator receptor gamma coactivator-1 alpha,PGC-1 α)和蛋白水解酶剪切Ⅲ型纤连蛋白组件包含蛋白5(fibrone-ctin type Ⅲ domain-containing protein 5,FNDC5)表达;免疫组织化学法检测心肌组织中FNDC5的表达.结果 与WT组相比,ob/ob组葡萄糖耐量、胰岛素耐量明显受损(P＜0.05);ob/ob组舒张期左室内径(diastolic left ventricular diameter,LVIDd)、收缩期左室内径(systolic left ventricular diameter,LVIDs)、舒张早期峰值血流速度(E峰)与舒张晚期峰值血流速度(A峰)的比值(E/A)等指标无明显变化(P＞0.05),但短轴缩短分数(fraction of shortening,FS)和射血分数(ejection fraction,EF)明显降低(P＜0.05),HE染色和Masson染色未发现明显的心肌细胞肥大及胶原沉积;心肌组织PGC-1α和FNDC5蛋白表达显著降低(P＜0.05).DHM干预16周后,显著改善葡萄糖耐量和胰岛素耐量受损、FS和EF的降低、PGC-1α和FNDC5蛋白表达的降低(P＜0.05).结论 DHM改善ob/ob小鼠心脏功能与PGC-1 α/FNDC5通路相关.

Dihydromyricetin improves cardiac function in ob/ob mice and its underlying mechanism

Objective To determine the protective effect of dihydromyricetin (DHM) on cardiac function in ob/ob mice (with leptin mutation) and investigate the underlying mechanism.Methods Thirtysix male ob/ob mice were randomly divided into 3 groups:ob/ob group,ob/ob + DHM 50 mg/kg group,ob/ob + DHM 100 mg/kg group (n =12).Ten C57BL/6J wild type mice are used as normal control (WT).Glucose tolerance and insulin tolerance were measured after 16 weeks' treatment.Cardiac function was detected by echocardiography.Myocardial histopathology and collagen deposition were detected by HE and Masson staining.The protein expression levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and fibronectin type Ⅲ domain-containing protein 5 (FNDC5) in the myocardium were detected by Western blotting.The expression of FNDC5 in the myocardium was observed by immunohistochemical assay.Results Glucose tolerance and insulin tolerance were obviously injured in the ob/ob mice than the WT group (P ＜ 0.05).In the ob/ob mice,no changes were found in diastolic left ventricular diameter (LVIDd),systolic left ventricular diameter (LVIDs),or ratio of velocity of early filling wave (E) to velocity of late filling wave due to atrial contraction (A) (P ＞ 0.05),or myocardial hypertrophy or collagen deposition,but notable decreases were found in short axis fractional shortening (FS) and ejection fraction (EF) (P ＜0.05),as well as the protein expression levels of PGC-1α and FNDC5 (P ＜0.05).DHM treatment for 16 weeks could significandy reverse the above changes in the ob/ob mice (P ＜0.05).Conclusion DHM ameliorates cardiac function in the ob/ob mice,which might be related to PGC-1 α/FNDC5 signalling pathway.