藏红花酸预处理对大鼠心肌缺血再灌注损伤中炎症反应和细胞凋亡的影响及其机制

Effect of Crocetin Pretreatment on Inflammatory Reaction and Apoptosis of Myocardial Ischemiareperfusion Injury in Experimental Rats

目的:探讨藏红花酸预处理对大鼠心肌缺血再灌注损伤中炎症反应和细胞凋亡的影响及其机制。方法:将30只Wistar雄性大鼠随机分为假手术组,缺血再灌注组,藏红花酸组,每组10只,术前7天分别给予相应处理。采用结扎冠状动脉左前降支的方法建立心肌缺血再灌注模型,缺血45 min后再灌注3 h。实验结束后用酶联免疫吸附法(ELISA)检测大鼠血清肌酸激酶MB同工酶(CK-MB)、肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)的含量,脱氧核苷酸末端转移酶介导的d UTP缺口末端标记法(TUNEL)检测心肌细胞的凋亡指数。结果:与假手术组相比,缺血再灌注组及藏红花酸组血清CK-MB和TNF-α含量明显上升(P<0.01),藏红花酸组IL-10含量明显上升(P<0.01),差异均有统计学意义。与缺血再灌注组相比,藏红花酸组的血清CK-MB、TNF-α含量及心肌细胞凋亡指数明显降低(P<0.01),差异有统计学意义;而血清IL-10含量明显升高(P<0.01),差异有统计学意义。结论:藏红花酸预处理在心肌缺血再灌注损伤中可以通过负性调节TNF-α,正性调节IL-10来减轻炎症反应并抑制心肌细胞的凋亡,发挥心肌保护作用。

Objective： To explore the effect and mechanism of crocetin （CRO） pretreatment on inflammatory reaction and apoptosis of myocardial ischemia-reperfusion （I/R） injury in experimental rats. Methods： A total of 30 male Wistar rats were randomly divided into 3 groups： Sham group, the rats received intragastric sodium carboxymethyl cellulose （CMC-Na） for 7 days followed by the operation without occlusion. I/R group, the rats received intragastric CMC-Na for 7 days followed by left anterior descending （LAD） coronary artery occlusion for 45 min with subsequent reperfusion for 3 hours. CRO group, the rats received intragastric crocetin 50 mg/（kg.day） for 7 days followed by I/R procedure. n=7 in each group. The levels of creatine kinase-MB （CK-MB）, tumor necrosis factor-α （TNF-α） and inlfammation cytokine interleukin-10 （IL-10） were examined by ELISA, the myocardial apoptosis index was determined by TUNEL staining. Result： Compared with Sham group, I/R group and CRO group had increased levels of CK-MB, TNF-α, and CRO group had increased IL-10 level, all P〈0.01. Compared to I/R group, CRO group showed decreased levels of CK-MB, TNF-αand myocardial apoptosis index, while increased IL-10 level, all P〈0.01. Conclusion： Crocetin pretreatment could down-regulate TNF-α expression, up-regulate IL-10 expression and therefore reducing the inlfammatory reaction in experimental rats to protect myocardial apoptosis.