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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C57BL/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-1alpha,PGC-1α)和蛋白水解酶剪切Ⅲ型纤连蛋白组件包含蛋白5(fibrone-ctin typeⅢdomain-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-1α/FNDC5通路相关。
Objective To investigate the protective effect of dihydromyricetin (DHM) on cardiac function in leptin mutant ob / ob mice and its related molecular mechanism. Methods Thirty - six male ob / ob mice were randomly divided into ob / ob group, 50 mg / kg DHM group (ob / ob + DHM 50 mg / kg), and 100 mg / kg DHM group ob + DHM 100 mg / kg), 12 in each group for 16 weeks. Ten C57BL / 6J wild-type mice served as normal control group (WT). The cardiac function was measured by echocardiography. The myocardial morphology and collagen deposition were detected by HE and Masson staining. The expressions of peroxisome proliferator-activated receptor-γ coactivator-1α proliferator activator receptor gamma coactivator-1alpha (PGC-1α) and fibronectin type Ⅲ domain-containing protein 5 (FNDC5) were detected by immunohistochemistry. FNDC5 expression. Results Compared with the WT group, the impaired glucose tolerance and insulin resistance were significantly impaired in the ob / ob group (P <0.05). The diastolic left ventricular diameter (LVIDd), systolic left ventricular diameter and left ventricular diameter (LVIDs). There was no significant change in the ratio of E / A between early diastolic peak velocity (E peak) and late diastolic peak flow velocity (A peak) (P> 0.05) Fractional shortening (FS) and ejection fraction (EF) were significantly decreased (P <0.05). No significant hypertrophy and collagen deposition were found in HE staining and Masson staining. The expressions of PGC-1α and FNDC5 The expression was significantly decreased (P <0.05). After 16-week intervention with DHM, impaired glucose tolerance and impaired insulin resistance, decreased FS and EF, and decreased PGC-1α and FNDC5 protein expression (P <0.05). Conclusions DHM improves cardiac function in ob / ob mice and is associated with PGC-1α / FNDC5 pathway.