丹参酮Ⅱ_A对鼠脑缺血再灌注损伤凋亡基因表达的影响

Effect of Tanshinone Ⅱ_A on Expression of Bcl-2 and Bax after Cerebral Ischemic Reperfusion Injury in Rats

目的探讨丹参酮ⅡA(TanⅡA)对脑缺血再灌注损伤大鼠B细胞淋巴瘤/白血病基因-2(Bcl-2)及B细胞淋巴瘤/白血病基因伴随蛋白x(Bax)蛋白表达的影响。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高、低剂量治疗组分别于术前连续灌胃给予相应剂量TanⅡA3 d,1次/d。除假手术组外的各组于脑缺血90 min再灌注24 h,进行HE染色观察病理形态学变化和神经症状评分,免疫组化法观察大鼠额顶部皮质Bcl-2和Bax蛋白表达。结果TanⅡA高、低剂量治疗组脑组织缺血损伤病理学改变明显轻于缺血再灌注组,TanⅡA高剂量治疗组缺血改变亦轻于低剂量治疗组。TanⅡA高、低剂量治疗组神经功能缺失评分较缺血再灌注组降低(P<0.05)。与假手术组比较,缺血再灌注组Bcl-2和Bax表达增加,Bcl-2/Bax比值下降(P<0.05)。与缺血再灌注组比较,TanⅡA高、低剂量治疗组均显著增加Bcl-2表达、减少Bax表达,上调Bcl-2/Bax比值,高、低剂量组之间差异亦具有显著性(P<0.05)。结论TanⅡA对缺血再灌注脑损伤具有保护作用,其机制可能与通过增加Bcl-2表达,减少Bax表达,上调Bcl-2/Bax比值抗凋亡有关。

Objective To study the effect of Tanshinone ⅡA （ Tan ⅡA ） on expression of Bcl - 2 and Bax of cerebral ischemia reperfusion（l/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 Tan ⅡA treated group and high dose Tan ⅡAtreated group. The focal middle cerebral artery occlusion（MCAO） model was made by suture - occluded method. Rats were pretreated with Tan ⅡA ,ig for 3 d, respectively before MCAO. After 90rain MCAO following 24 h of reperfusion, HE staining and the neurological score were investigated . Expression of Bcl - 2 and Bax were also investigated with immunohistoehemistry. Results The changes of isehemie impairment in low and high dose Tan ⅡA treated groups were lighter than in IR group, and was lighter in high dose Tan ⅡA treated group than in low dose Tan ⅡA treated group. Compared with IR group, the neurological score was decreased in low and high dose Tan ⅡA treated group （ all P 〈 0.05 ）. Compared with sham operated group , expression of Bcl - 2 and Bax increased at 24h of reperfusion in the isehemic territory（ P 〈 0.05 ） ; and the ratio of Bel - 2/Bax was decreased . Compared with I/R group, low and high dose Tan ⅡA treated group increased expression of Bcl - 2 and reduced expression of Bax dose - dependently （ P 〈 0.05 ） , the ratio of Bel - 2/Bax was increased . Conclusion Tan ⅡA may reduce cerebral ischemia - reperfusion injury by increasing the expression of Bcl - 2 and decreasing the expression of Bax. It plays protective effect from apoptosis through increasing the ratio of Bcl -2/Bax.