青藤碱对糖尿病大鼠脑缺血再灌注损伤P-选择素和细胞间黏附分子-1表达的影响

Effect of Sinomenine on Expression of P-selectin and ICAM-1 Following Cerebral Ischemic Reperfusion Injury in Diabetic Rats

目的探讨青藤碱(sinomenine,Sin)对糖尿病大鼠脑缺血再灌注损伤P-选择素和细胞间黏附分子-1(ICAM-1)表达的影响。方法采用高脂高糖饮食加腹腔注射小剂量链脲霉素建立糖尿病大鼠模型,造模成功后将大鼠随机分为假手术组、缺血再灌注组、Sin低剂量治疗组和Sin高剂量治疗组。线栓法建立局灶性脑缺血再灌注模型。Sin低(30mg/kg),高剂量(60mg/kg)治疗组于术前30min分别给予大鼠腹腔注射。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2,3,5-三苯基氯化四氮唑(TTC)染色和HE染色观察脑梗死体积及病理形态学变化。结果①糖尿病大鼠脑缺血再灌注24h,P-选择素和ICAM-1表达均明显增加,与假手术组比较,差异具有显著性(均P<0.05);与缺血再灌注组比较,Sin高、低剂量治疗组均显著减少P-选择素和ICAM-1表达(均P<0.05),高、低剂量组之间差异亦具有显著性(P<0.05)。②Sin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具有显著性(P<0.05)。③Sin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,Sin高剂量治疗组缺血改变亦轻于低剂量治疗组。结论Sin对糖尿病大鼠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所介导的炎症反应有关。

Objective To study the effect of sinomenine（Sin） on expression of P - selectin and ICAM - 1 following cerebral ischemia reperfusion（I/R） injury in diabetic rats. Methods In this experiment, rat model of diabetes mellitus was made by high sucrose, fat diet and streptozotion injection. Diabetic rats were randomly divided into 4 groups： sham operated group, I/R group, low dose Sin treated group and high dose Sin treated group. The focal middle cerebral artery occlusion（MCAO） model was made by suture - occluded method. Sin were given intraperitoneally to rats 30rain before focal cerebral ischemia operation respectively . After 90rain MCAO following 24 h of reperfusion, we investigated the expression of P - selectin and ICAM - 1 with immunohistochemistry in ischemic frontal and parietal cortex . HE staining and TTC staining were also investigated. Results ①Compared with sham operated group ,expression of P- selectin and ICAM -1 was increased at 24h of reperfusion in the ischemic territory（P 〈 0.05 ）. Compared with I/R group, low and high dose Sin treated group dose - dependently reduced the expression of P - selectin and ICAM - 1 （ all P 〈 0.05 ）. ②Compared with L/R group, cerebral infarction volume in low dose Sin treated group and high dose Sin treated group was decreased dose - dependently （ all P 〈 0.05 ）. ③The change of ischemic impairment in low or high dose Sin treated group was lighter than that of IR group, and high dose Sin treated group was lighter than that of low dose Sin treated group. Conclusion Sin may reduce cerebral ischemia - reperfusion injury by decreasing the expression of P - selectin and ICAM - lin diabetic rats.