丁苯酞对糖尿病大鼠局灶性脑缺血再灌注后B细胞淋巴瘤/白血病-2基因及其相关X蛋白表达的影响

Effect of Butylphthalide on the Expressions of Bcl-2 and Bax in Diabetes Rats with Focal Cerebral Ischemia-reperfusion Injury

目的:观察丁苯酞(Butylphthalide)对糖尿病大鼠局灶性脑缺血再灌注损伤后B细胞淋巴瘤/白血病-2(Bcl-2)和Bcl-2相关X蛋白(Bax)表达的影响,研究在糖尿病合并急性脑卒中患者的治疗中,丁苯酞所发挥的作用机制。方法:选取70只雄性SD大鼠,以简单随机数字法分为治疗组(n=30)、对照组(n=30)及假手术组(n=10)。三组以无菌链脲佐菌素腹腔内注射使实验动物达到糖尿病标准。假手术组切开右侧颈部皮肤,分离右侧颈动脉后,重新缝合皮肤;治疗组及对照组以栓线从右侧颈内动脉入口栓塞右侧大脑中动脉实现大脑中动脉闭塞及再灌注。再灌注30 min后,治疗组以80 mg/(kg·d)丁苯酞剂量灌胃,对照组及假手术组给予等量食用麻油灌胃,连续给药3 d。再灌注后72 h进行神经功能评分,最后以TUNEL法计算细胞凋亡数目,免疫组化检测Bcl-2及Bax表达。结果:治疗组神经功能评分低于对照组(P<0.05);治疗组的凋亡细胞数少于对照组(P<0.05);治疗组的Bcl-2表达高于对照组,而Bax表达低于对照组(P<0.05)。结论:丁苯酞对糖尿病合并急性脑梗死患者脑缺血半暗带中神经细胞凋亡的抑制作用可能是通过上调Bcl-2及下调Bax表达而实现。

Objective:To observe the effect of Butylphthalide on the expressions of Bcl-2 and Bax with focal cerebral ischemia-reperfusion injury in diabetes rats and to study the mechanism of Butylphthalide in the treatment of diabetic patients with acute stroke.Method:A total of 70 male SD rats were selected and divided into treatment group(n=30),control group(n=30)and sham operation group(n=10)by simple random number method.The three groups were injected intraperitoneally with sterile Streptozotocin to make the experimental animals reach the diabetic standard.In the sham operation group,the skin of the right neck was cut open and the right carotid artery was separated,then the skin was re-sutured.In the treatment group and the control group,the right middle cerebral artery occlusion and reperfusion were achieved by embolizing the right middle cerebral artery from the right internal carotid artery entrance.30 min after reperfusion,the treatment group was given 80 mg/(kg·d)Butylphthalide by gavage,and the control group and sham operation group were given the same amount of edible sesame oil by gavage for 3 consecutive days.Neurological function score was performed 72 h after reperfusion.Finally,TUNEL method was used to calculate the number of apoptosis cells.Immunohistochemistry was used to detect the expression of Bcl-2 and Bax.Result:The neurological deficit score of the treatment group was lower than that of the control group(P<0.05);the number of apoptotic neurons in the treatment group was less than that in the control group(P<0.05);the expression of Bcl-2 in the treatment group was higher than that in the control group,while the expression of Bax in the treatment group was lower than that in the control group(P<0.05).Conclusion:Butylphthalide may protect diabetes rats from neurons apoptosis after focal cerebral ischemia-reperfusion by promoting the expressions of Bcl-2 and inhibiting the expressions of Bax.