丹参酮ⅡA对脑缺血再灌注损伤大鼠脑组织及血清中NO含量及NOS、iNOS活性的影响

Effect of Tanshinone ⅡA on Content of NO and Activities of NOS and iNOS in Cerebral Ischemic Reperfusion Injury Rats

目的观察丹参酮ⅡA(TanⅡA)对脑缺血再灌注损伤大鼠脑组织及血清中一氧化氮(NO)含量、一氧化氮合酶(NOS)及诱导型一氧化氮合酶(iNOS)活性的影响,探讨其对脑缺血再灌注损伤保护作用的可能机制。方法将大鼠随机分为假手术组、缺血再灌注组、TanⅡA低、高剂量组,线栓法建立局灶性脑缺血再灌注模型。TanⅡA高、低剂量组于术前连续灌胃给予高、低剂量TanⅡA3d,每日1次。各组于脑缺血90min再灌注24h后进行HE染色,观察病理形态学变化,检测脑组织和血清中NO含量和NOS、iNOS活性的变化。结果TanⅡA高、低剂量组脑组织缺血损伤病理学改变明显轻于缺血再灌注组,TanⅡA高剂量组缺血改变亦轻于低剂量组。与假手术组比较,缺血再灌注组脑组织和血清中NO含量和NOS、iNOS活性明显升高;与缺血再灌注组比较,TanⅡA高、低剂量组脑组织和血清中NO含量和NOS、iNOS活性均明显降低,高、低剂量组之间差异具有统计学意义(P<0.05)。结论TanⅡA可减轻神经元损伤程度,对缺血再灌注脑损伤具有保护作用,其机制可能与降低NOS、iNOS活性,减少NO含量有关。

Objective To study effect of Tanshinone ⅡA （Tan ⅡA） on the content of NO and the activities of NOS and iNOS in cerebral ischemia reperfusion {I/R） injury rats, and explore its protective mechanism. Methods Rats were randomly divided into 4 groups, which were sham operated group, I/R group, low dose Tan Ⅱ A treated group and high dose Tan Ⅱ A treated group. The focal middle cerebral arterymocclusion （MCAO） model was made by suture-occluded method. Rats were pretreated with Tan Ⅱ A, ig for 3 d before MCAO. After 90 min MCAO following 9.4 h of reperfusion, pathomorphologic changes was investigated with HE staining. The content of NO and the activities of NOS and iNOS was also determined. Result The change of ischemic impairment in low or high dose Tan ⅡA treated group was lighter than that of I/R group, and high dose Tan ⅡA treated group was lighter than that of low dose Tan ⅡA treated group. Compared with sham operated group, the content of NO and the activities of NOS and iNOS increased at 24 h of reperfusion in the ischemic territory （P〈0.05）. Compared with I/R group, low and high dose Tan ⅡA treated group reduced the content of NO and the activities of NOS and iNOS dose-dependently （P〈0.05）. Conclusion Tan ⅡA has protective effect on cerebral I/R injury by reducing the content of NO and the activities of NOS and iNOS dose-dependently.