丹参酮ⅡA对大鼠脑缺血-再灌注损伤细胞间黏附分子-1表达及髓过氧化物酶活性的影响

Effects of tanshinone ⅡA on the expression of ICAM-1 and MPO activity of cerebral ischemia-reperfusion injury in rats

目的探讨丹参酮ⅡA对脑缺血-再灌注损伤大鼠的保护作用及其对细胞间黏附分子-1表达及髓过氧化物酶活性的影响。方法80只Wistar大鼠随机分为假手术组、缺血-再灌注组(缺血组)、丹参酮ⅡA小剂量治疗组[小剂量组,15mg/(kg·d)]和丹参酮ⅡA大剂量治疗组[大剂量组,30mg/(kg·d)];线拴法建立局灶性脑缺血-再灌注大鼠模型,治疗组大鼠于手术前连续生理盐水灌胃后给予不同剂量的丹参酮ⅡA。免疫组织化学方法观察脑缺血-再灌注大鼠额顶叶皮质细胞间黏附分子-1表达水平、髓过氧化物酶活性、脑组织含水量及梗死灶体积。结果脑缺血-再灌注后24h,缺血组细胞间黏附分子-1表达阳性的血管数为(63.00±4.74)根/5个高倍视野,髓过氧化物酶活性为(0.42±0.04)U/g,与假手术组[0和(0.03±0.01)U/g]比较,差异有统计学意义(均P<0.01);小剂量组细胞间黏附分子-1表达阳性的血管数为(41.20±4.55)根/5个高倍视野,髓过氧化物酶活性为(0.33±0.02)U/g,大剂量组分别为(26.40±3.78)根/5个高倍视野和(0.23±0.03)U/g,均低于缺血组(P<0.01),两剂量组之间比较差异有统计学意义(P<0.01)。缺血组脑组织含水量为(92.13±2.62)%,梗死灶体积为(194.10±10.99)mm3,与假手术组[(81.09±1.47)%和0]比较差异有统计学意义(均P<0.01);小剂量组脑组织含水量为(87.88±1.86)%,梗死灶体积为(140.86±5.25)mm3,大剂量组分别为(83.36±2.90)%和(112.20±10.78)mm3,均低于缺血组(P<0.01),两剂量组之间比较差异有统计学意义(P<0.01)。结论丹参酮ⅡA对脑缺血-再灌注损伤具有保护作用,其机制可能与缺血-再灌注后细胞间黏附分子-1表达水平和中性粒细胞浸润受到抑制有关。

Objective To study the effects of tanshinone Ⅱ A （Tan Ⅱ A） on the expression of intercellular adhesion molecule-1 （ICAM-I） and myeloperoxidase （MPO） activity of cerebral ischemia- reperfusion （IR） injury in rats. Methods Eighty Wistar rats were randomly divided into 4 groups： sham operated group, IR group, Tan Ⅱ A low dose [15 mg/（kg·d）] group and Tan Ⅱ A high dose [30 mg/（kg·d）] group. The model of focal middle cerebral artery occlusion （MCAO） was developed by suture-occluded method. Rats in Tan ⅡA groups were pretreated before MCAO with saline and assigned dose of Tan ⅡA through gastric peffusion, every day, for 3 d. Rats in sham operated group and IR group were all pretreated with the same volume of saline through gastric perfusion before MCAO. The expression of ICAM-1 in the frontal and parietal cortex of cerebral ischemia-reperfusion rats was detected by immunohistochemistry, and MPO activity was also assessed. Brain water content and cerebral infarction volume were also investigated. Results After 24 h-cerebral ischemia-reperfusion, the number of ICAM-t positive expression vessels was （63.00± 4.74） / 5 high power fields and MPO activity was （0.42± 0.04） U/g in IR group, and there were significant differences in comparison with those in sham operated group [0 and （0.03 ± 0.01 ） U/g] （P〈0.01, for all）. In Tan Ⅱ A low and high dose groups, the numbers of ICAM-1 positive expression vessels were （41.20±4.55）/5 high power fields and （26.40± 3.78）/5 high power fields, and the MPO activity were （0.33 ± 0.02） U/g and （0.23 ±0.03） U/g respectively, they were all lower than those in IR group （P〈0.01）, and there were significant differences between Tan ⅡA low and high dose group （P〈0.01）. The blain water content was （92.13 ±2.62）% and cerebral infarction volume was （194.10±10.99） mm3 in IR group,and there were significant differences in comparison with those in sham operated group [（81.09± 1.47）% and 0] （P〈 0.01, for all）. In Tan Ⅱ A low and high dose groups, the brain water content were （87.88 ± 1.86）% and （83.36±2.90）%, and cerebral infarction volume were （140.86 ± 5.25） mm3 and （112.20 ± 10.78） mm3 respectively, they were all lower than those in IR group （P〈0.01）, and there were significant differences between Tan Ⅱ A low and high dose group （P 〈 0.01）. Conclusion Tanshinone Ⅱ A has protective effect on brain after cerebral ischemia-reperfusion injury. It may be correlated with the inhibiting of inflammatory reaction in cerebral ischemia-reperfusion by decreasing the expression of ICAM-1 and neutrophil infiltration.