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目的卡维地洛在实验性心脏损伤模型中具有显著的心脏保护作用。本研究探讨是否卡维地洛能减轻自身免疫性心肌炎,并探讨其可能的主要机制。方法 6周龄Lewis大鼠诱导自身免疫性心肌炎,随机分为正常对照、阳性对照、不同剂量的卡维地洛、美多洛尔、普萘洛尔、以及卡维地洛消旋体治疗组。观察其对急性心肌炎症程度,及对炎症心肌内多种炎性细胞因子mRNA表达及蛋白表达、心肌细胞内蛋白氧化产物和细胞膜脂质过氧化产物TBARS含量的影响。结果尽管两种剂量的卡维地洛、美多洛尔和普萘洛尔显示出同等的β受体阻滞作用,只有卡维地洛治疗使心肌炎症得到减轻,心重/体重、炎症分级严重程度明显减轻;卡维地洛消旋体虽无β受体阻滞作用,但心肌炎严重程度也明显减轻;与阳性对照组比较,卡维地洛治疗显著降低蛋白羧基含量和TBARS产物,而美多洛尔和普萘洛尔治疗组则无明显变化;也只有卡维地洛治疗明显降低心肌炎性细胞因子mRNA表达和IL-1β表达。体外实验证实卡维地洛和卡维地洛消旋体保护离体心肌细胞膜的脂质过氧化、并以剂量依赖方式抑制培养的U937细胞LPS刺激后IL-1β释放。结论卡维地洛治疗减轻自身免疫性心肌炎,其心脏保护作用可能与其抗氧化和抑制炎症细胞因子作用有关。
Objective Carvedilol has a significant cardioprotective effect in a model of experimental heart injury. This study explored whether carvedilol can reduce autoimmune myocarditis and explore its possible main mechanism. Methods Six-week-old Lewis rats were induced with autoimmune myocarditis and randomly divided into normal control, positive control, different doses of carvedilol, metoprolol, propranolol, and carvedilol racemate . To observe the degree of acute myocardial inflammation, and a variety of inflammatory cytokines in inflammatory myocardium mRNA expression and protein expression, myocardial cell protein oxidation products and membrane lipid peroxidation product TBARS content. Results Although carvedilol, metoprolol and propranolol showed equivalent β blockade at both doses, only carvedilol treatment reduced myocardial inflammation, severe heart / body weight, and severe grading of inflammation Although the activity of carvedilol was not blocked by β-receptor but the severity of myocarditis was significantly reduced. Compared with the positive control group, carvedilol treatment significantly reduced the protein carboxyl content and TBARS production, while the beauty Dolorol and propranolol treatment group had no significant change; only carvedilol treatment significantly decreased myocardial inflammatory cytokines mRNA expression and IL-1β expression. In vitro experiments confirmed that carvedilol and carvedilol racemic protection of myocardial cell membrane lipid peroxidation and a dose-dependent inhibition of cultured U937 cells LPS-induced IL-1β release. Conclusion Carvedilol can reduce the autoimmune myocarditis and its cardioprotection may be related to its anti-oxidation and anti-inflammatory cytokines.