丹参酮ⅡA对脑缺血再灌注损伤大鼠P-选择素和细胞间黏附分子-1表达及髓过氧化物酶活性的影响

Effects of Tanshinone ⅡA on Expression of P-selectin,ICM-1 and MPO Activity following Cerebral Ischemic Reperfusion Injury in Rats

目的探讨丹参酮ⅡA(TanⅡA)对缺血再灌注损伤大鼠P-选择素和细胞间黏附分子-1(ICAM-1)表达及髓过氧化物酶(MPO)活性的影响。方法将大鼠随机分为假手术组、缺血再灌注组、TanⅡA低剂量治疗组和TanⅡA高剂量治疗组,线栓法建立局灶性脑缺血再灌注模型。TanⅡA治疗组于术前连续灌胃给药3d,每日1次。用免疫组化法观察缺血90min再灌注24h大鼠额顶部皮质P-选择素和ICAM-1表达,进行MPO活性检测,进行2,3,5-三苯基氯化四氮唑(TTC)染色观察脑梗死体积。结果脑缺血90min再灌注24h,缺血再灌注组P-选择素和ICAM-1表达明显增加,与假手术组差异显著;与缺血再灌注组比较,TanⅡA高、低剂量治疗组均显著减少P-选择素和ICAM-1表达,高、低剂量组之间差异亦显著。脑缺血90min再灌注24h,缺血再灌注组MPO活性明显增加,与假手术组差异显著;与缺血再灌注组比较,TanⅡA高、低剂量治疗组均显著减少MPO活性,高、低剂量组之间差异亦显著。TanⅡA治疗组脑梗死体积较缺血再灌注组减小,高、低剂量组之间差异亦显著。结论TanⅡA对缺血再灌注脑损伤具有保护作用,其机制可能与减轻脑缺血再灌注损伤阶段P-选择素和ICAM-1所介导的中性粒细胞浸润的炎症级联反应有关。

Objective： To study the effects of Tanshinone ⅡA （Tan ⅡA ）on expression of P - selectin, ICAM - 1 and MPO activity of cerebral ischemia reperfusion （I/R） injury in rats. Methods： In this experiment, rats were randomly divided into 4 groups, which were sham operated group, I/R group, low dose and high dose Tan HA treatment group. The focal middle cerebral artery occlusion （MCAO） model was made by suture - occluded method. The rats were pretreated with Tan ⅡA ig for 3d, respectively before MCAO. The after 90rain MCAO and following 24h of reperfusion, the ex- pression of P - selectin and ICAM - 1 and the MPO activity were investigated by immunohistochemistry. TTC staining was used to determine the volume of cerebral infarction. Results： Compared with sham operated group, the expression of P - selectin and ICAM - 1 increased at 24h of reperfusion in the ischemic territory. Compared with I/R group, low and high dose Tan ⅡA treatment group dose - dependently reduced expression of P - selectin and ICAM - 1. Compared with sham operated group, the MPO activity increased at 24h of reperfusion in the ischemic territory. Compared with I/R group, low and high dose Tan ⅡA treatment group dose - dependently reduced the MPO activity. Compared with that of I/R group, cerebral infarction volume of low dose and high dose TanⅡA treatment group was decreased dose - depen- dently. Conclusion： Tan HA may reduced cerebral I/R inflammation injury by decreasing the expression of P - selectin, ICAM - 1 and MPO activity. It plays protective effect on cerebral ischemia injury.