柚皮素对缺血再灌注损伤细胞间黏附分子-1和核因子-κB的影响

Effects of Naringenin on ICAM-1 and NF-κB Activities Following Myocardial Ischemia/Reperfusion Injury

目的探讨柚皮素(NAR)对心肌缺血再灌注(MI/R)损伤大鼠细胞间黏附分子-1(ICAM-1)和核因子-κB(NF-κB)的影响。方法采用结扎左冠脉前降支30 min再灌注2 h的方法复制MI/R损伤大鼠模型,随机分为5组(n=10):假手术组,模型组,NAR高、中、低剂量组(100、50、25 mg·kg-1),于术前1周开始腹腔注射给药,每日1次。再灌注后取心脏,染色法测定心肌梗死面积;免疫组化法测定心肌组织NF-κB和ICAM-1表达情况;取心肌匀浆,髓过氧化物酶(MPO)法测定中性粒细胞浸润情况。结果 NAR高剂量可缩小心肌梗死面积至32.91%,与模型组(39.78%)比较差异有统计学意义(P<0.05);NAR各剂量组心肌MPO活力分别降低至330.54、322.74、280.64 U·g-1,与模型组(423.9 U·g-1)比较差异均有统计学意义(P<0.05或P<0.01);与模型组(65.22%)比较,NAR各剂量组心肌组织ICAM-1阳性表达分别降低到50.12%、44.75%、42.05%(P<0.01);与模型组(38.41%)比较,NAR各剂量可使心肌组织NF-κB的阳性表达分别降低至32.05%、30.22%、29.16%(P<0.05或P<0.01)。结论 NAR预处理通过抑制中性粒细胞浸润,下调NF-κB和ICAM-1的表达,抑制炎症反应,进而实现对MI/R所致心肌损伤的保护作用。

Objective To investigate the effects of naringenin （NAR） on ICAM-1 and NF-κB activities in rats following myocardial ischemia/reperfusion （MI/R） injury. Methods Rat model of MI/R injury was established by coronary artery ligation for 30 min followed by 2-hour reperfusion. Then rats were divided randomly into 5 groups （n=10）, namely sham, model and NAR groups （100, 50 and 25 mg·kg-1）. NAR was administered by intraperitoneal injection once a day for 7 days pre-operation. The size of myocardial infarction was measured by NBT staining after the reperfusion. The myocardial ICAM-1 and NF-κB activities were detected by immunohistochemistry. The MPO activity in heart homogenate was detected by chromatometry to evaluate the neutrophil infiltration. Results NAR （100 mg·kg-1） reduced the size of myocardial infarction to 32.91%, showing a significant difference compared to 39.78%of model group（P〈0.05）. The MPO activities in NAR groups were 330.54, 322.74 and 280.64 U·g-1, respectively, which were significantly lower than 423.9 U·g-1 of model group （P〈0.05 or P〈0.01）. NAR evidently reduced the ICAM-1 positive rates in heart to 50.12%, 44.75% and 42.05%, respectively, comparing to 65.22% of model group （P〈0.01）. Similarly, NAR significantly reduced the NF-κB positive rates to 32.05%, 30.22% and 29.16%, respectively, comparing to 38.41% of model group （P〈0.05 or P〈0.01）. Conclusion The myocardial protection of NAR pretreatment in MI/R injury appears to be associated with the inhibition of neutrophil infiltration, expression of ICAM-1 and NF-κB and inflammatory response.