棉子酚通过干扰氧化应激反应、抑制JNK/p38 MAPK信号通路的激活减轻大鼠离体心脏缺血再灌注损伤

Gossypol alleviates isolated heart ischemia/reperfusion injury in rats by interfering with the oxidative stress response and suppressing the JNK/p38 MAPK signal pathway

目的研究棉子酚(Gossypol)对大鼠离体心脏缺血再灌注损伤的保护作用,并对其可能的机制进行初步探讨。方法 SD雄性大鼠40只,随机分成4组:空白组、心肌缺血再灌注组(MI/R组)、Gossypol高、低剂量组(40、20 mg/L)。采用Langendorff法造模,检测Gossypol对血流动力学指标的影响及不同时间点各组动物心脏冠脉流出液中心肌酶谷草转氨酶(AST)、乳酸脱氢酶(LDH)的含量,检测炎性细胞因子核转录因子(NF)-κB、细胞间黏附分子(ICAM)-1、肿瘤坏死因子(TNF)-α和白介素(IL)-6生成量,从氧化应激反应、JNK/p38 MAPK信号通路方面探讨Gossypol对早期MI/R的保护机制。结果各组Gossypol均可显著改善MI/R大鼠的心功能,减少AST、LDH释放,增加超氧化物歧化酶的活性,减少丙二醛的产生,减少再灌注的心肌组织中炎性细胞因子生成量。机制研究表明其可能通过清除自由基、抗脂质过氧化、阻断JNK/p38 MAPK信号通路途径的激活缓解心脏缺血再灌注所造成的氧化应激损伤和凋亡损伤。结论Gossypol对MI/R具有保护作用,其机制可能与干扰氧化应激反应及阻断JNK/p38 MAPK信号通路途径的激活有关。

Objective To investigate the protective effect and possible mechanism of Gossypol on isolated myocar- dial ischemia/reperfusion injury in rats. Methods 40 male Sprague-Dawley rats were randomly divided into 4 groups： Blank group, heart ischemia reperfusion group （MI/R group） high and low-dose Gossypol group （40,20 mg/L）. The model of the myocardial ischemiafreperfusion injury were established using the Langendorff mem- od. The hemodynamicsindexes, cardiac enzymes AST and LDH, inflammatory cytokines （ NF-KB, ICAM-1, TNF-ot and IL-6） were measured. The effect and mechanism of Gossypol on early-stage MIfR of the oxidative stress re- sponse and the JNK/p38 MAPK signal pathway were investigated. Results Experimental results showed that Gos- sypol could significantly improve the functional capacity of the heart, reduce the contents of AST, LDH and inflam- matory cytokines in reperfused heart tissue, and increase superoxide dismutase levels to protect the heart. The mechanism of this substance may involve anti-lipid peroxidation and inhibition of p38 kinase phosphorylation and JNK, and reduction of oxidative stress injury and apoptosis damage induced by MI/R. Conclusion This study con- firm that Gossypol exerts extensive anti-MI/R effects. Its mechanism may be related to the interfering with the oxida- tive stress response and suppressing the JNK/p38 MAPK signal pathway.