青藤碱对大鼠局灶性脑缺血再灌注损伤保护作用及机制

Mechanism of neuroprotective effect of sinomenine after focal cerebral ischemia reperfusion injury in rats

目的探讨青藤碱(Sin)对脑缺血再灌注损伤保护作用及机制。方法将80只Wistar大鼠随机分为假手术组、脑缺血再灌注组、Sin低剂量治疗组和Sin高剂量治疗组。用线栓法建立大脑中动脉局灶性缺血再灌注模型。于术前30min分别给予治疗组动物Sin30、60mg/kg腹腔注射。各组动物于脑缺血90min再灌注24h,取脑标本采用TUNEL法检测神经细胞凋亡,干湿质量法检测脑含水量,HE染色观察脑组织病理改变,分光光度法检测髓过氧化物酶(MPO)活性,羟胺法和硫巴比妥酸盐反应法检测超氧化物歧化酶(SOD)和丙二醛(MDA)变化。结果 (1)与假手术组比较,脑缺血再灌注组凋亡细胞和脑含水量明显增加(P<0.05);与脑缺血再灌注组比较,Sin高、低剂量治疗组凋亡细胞均明显减少,脑含水量降低,Sin高剂量治疗组凋亡细胞减少,脑含水量降低较Sin低剂量治疗组更明显(P<0.05)。(2)与假手术组比较,脑缺血再灌注组MPO活性和MDA含量明显增加,SOD活性下降;与脑缺血再灌注组比较,Sin高、低剂量治疗组MPO及MDA含量均明显减少,SOD活性提高;Sin高剂量治疗组MPO及MDA含量减少、SOD活性提高较Sin低剂量治疗组更明显(P<0.05)。(3)Sin高、低剂量治疗组脑组织缺血损伤病理学改变明显轻于脑缺血再灌注组,Sin高剂量治疗组缺血改变亦轻于Sin低剂量治疗组。结论 Sin对脑缺血再灌注损伤有保护作用,其机制可能与抗凋亡、抑制炎症反应和自由基生成有关。

Objective To explore the mechanism of neuroprotective effects of sinomenine after 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 sinomenine treated group and high sinomenine treated group.The focal middle cerebral artery occlusion（MCAO）model was made by suture-occluded method.Sinomenine were given intraperitoneally to rats 30 min before focal cerebral ischemia operation respectively.After 90 min MCAO following 24 h of reperfusion,we investigated the neural cell apoptosis with TUNEL.Brain water content of the ischemic areal and HE staining were also investigated.The MPO activity and the content of SOD and MDA were also investigated.Results（1）Compared with sham operated group,neural cell apoptosis rate and brain water content increased at 24 h of reperfusion in the ischemic territory（P0.05）.Compared with I/R group,low and high dose sinomenine treated group reduced neural cell apoptosis rate and brain water content dose-dependently（P0.05）.（2）Compared with sham operated group,MPO activity and the content of MDA were higher,SOD activity was lower in I/R group.Compared with I/R group,sinomenine treament group may reduced MPO activity and the content of MDA,increased the content of SOD dose-dependently（P0.05）（3）The change of ischemic impairment in low or high dose sinomenine treated group was lighter than that of IR group,and high dose sinomenine treated group was lighter than that of low dose sinomenine treated group.Conclusion Sinomenine may reduced cerebral ischemia-reperfusion injure by decreasing neural cell apoptosis.and inflammation reaction and free radicals.