摘要
目的评价NSC23766对糖尿病大鼠局灶性脑缺血再灌注损伤的影响。方法健康成年雄性SD大鼠,2~3月龄,体重250—300g,采用腹腔注射链脲佐菌素60mg/kg的方法制备糖尿病模型。取糖尿病模型制备成功的大鼠51只,采用随机数字表法,将其随机分为3组(n=17):假手术组(S组)、缺血再灌注组(I/R组)和Racl特异性抑制剂NSC23766组(N组)。I/R组和N组采用线栓法制备局灶性脑缺血再灌注损伤模型,N组于缺血前15min经侧脑室注射NSC2376650μg,S组与I/R组给予等容量生理盐水。于再灌注24h时进行神经功能缺陷评分,然后处死大鼠,取脑组织,测定脑梗死体积,HE及Nissl染色,光镜下观察病理学结果,并测定细胞凋亡指数和p38丝裂原活化蛋白激酶(p38MAPK)磷酸化水平。结果与S组比较,I/R组和N组神经功能缺陷评分和细胞凋亡指数升高,脑梗死体积增大,p38MAPK磷酸化水平上调(P〈0.05);与I/R组比较,N组神经功能缺陷评分和细胞凋亡指数降低,脑梗死体积缩小,p38MAPK磷酸化水平下调(P〈0.05)。结论NSC23766可减轻糖尿病大鼠局灶性脑缺血再灌注损伤。
Objective To investigate the effects of NSC23766 on focal cerebral ischemia-repeffusion (I/ R) injury in diabetic rats.Methods Fifty-one male Sprague-Dawley rats, aged 2-3 months, weighing 250-300 g, in which diabetes mellitus was successfully induced by intraperitoneal streptozotocin 60 mg/kg, were randomly as- signed into 3 groups (n = 17 each): sham operation group (group S), focal cerebral [/R group (group I/R) and specific Rael inhibitor NSC23766 group (group N). Focal cerebral I/R was induced by middle cerebral arterial oc- clusion in groups I/R and N. In group N, NSC23766 (50μg) was injected into the cerebral lateral ventricle at 15 rain before ischemia, while the equal volume of normal saline was injected in groups S and I/R. Neurological defi- cits were scored at 24 h of repeffusion. The rats were then sacrificed and the brains were removed for determination of infarct volume (by TFC staining), apoptosis (by TUNEL) and phosphorylation of p38MAPK (by Western blot) and for microscopic examination (by HE and Nissl staining). Apoptotic index was calculated. Results Compared with group S, the neurological deficit scores and apoptotic index were significantly increased, the infarct volume was enlarged, and the phosphorylation of p38MAPK was significantly increased in groups I/R and N (P 〈 0.05). The neurological deficit scores and apoptotic index were significantly lower, and the infarct volume was significantly smaller, and the phosphorylation of p38MAPK was significantly lower in group N than in group I/R ( P 〈 0.05 ). Conclusion NSC23766 can reduce focal cerebral I/R injury in diabetic rats.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2012年第9期1143-1145,共3页
Chinese Journal of Anesthesiology