D半乳糖诱导结合双血管结扎建立脑缺血大鼠模型及其评价

Establish and evaluation of rat cerebral ischemia model induced by D-galactose combined with ligation of bilateral common carotid arteries

目的通过D半乳糖(D-gal)诱导结合双血管结扎的方法建立一种能较好地模拟人类脑缺血的动物模型,并对该模型进行评价。方法以3月龄青年SD大鼠为实验对象,采用D-gal连续皮下注射6周结合双血管结扎的方法制备脑缺血动物模型。以Garcia量表评价大鼠的神经功能损伤的严重程度;血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)水平评价机体氧自由基代谢情况;TTC染色评价大鼠脑梗死体积;HE染色评价缺血区脑组织损伤的严重程度。结果模型组(10.375±1.188)和半乳糖模型组Garcia评分(7.167±4.714)均低于空白组(20±0;均P<0.01),半乳糖模型组Garcia评分低于模型组(P<0.05)。与模型组比较,半乳糖模型组大鼠SOD〔(393.60±19.02)U/mL vs.(469.37±22.63)U/mL〕和GSHPx(1116.38±76.88 vs.1413.22±102.74)活性降低(均P<0.05),MDA〔(17.58±0.84)mmol/mL vs.(10.89±1.08)mmol/mL〕水平升高(P<0.05)。与模型组比较,半乳糖模型组梗死体积分数(35.75±2.38 vs.24.23±1.92)明显增大(P<0.01)。模型组大鼠缺血区表现为神经元细胞肿胀变性溶解,白质疏松等异常病理变化,半乳糖模型组较模型组更为严重。结论该模型能够较好地模拟人类脑缺血。

Objective To established animal model by D-galactose（gal）-inducing and double vascular ligation,and simulate the human brain ischemia and evaluate the model.Methods Cerebral ischemia models were established by the method of D-gal injected subcutaneously for 6weeks and then the operation of bilateral carotid artery ligation was taken in 3 month young Sprague-Dawley（SD）rats.The criteria of a successful model was evaluated by Bederson scale and the neurological dysfunction severity caused by cerebral ischemia was evaluated by Garcia scale.The serum superoxide dismutase（SOD）,glutathione peroxidase（GSH-Px）activity and Malondialdehyde（MDA）content were detected by chemical colorimetric method.The infarct size was evaluated by TTC staining.The injury severity of brain ischemic tissue was evaluated by HE staining.Results Compared to the blank group（20±0）,Garcia score of the model group（10.375±1.188）and the D-gal model group（7.167±4.714）showed significant differences（P0.01）.Compared to the model group,Garcia score of the D-gal model group（7.167±4.714 vs.10.375±1.188）decreased（P0.05）.Compared with the model group,serum SOD [（393.60±19.02）U/mL vs.（469.37±22.63）U/mL],GSH-Px（1116.38±76.88 vs.1413.22±102.74）activity of the D-gal model group were decreased（P0.05respectively）,MDA [（17.58±0.84）mmol/mL vs.（10.89±1.08）mmol/mL]content increased（P0.05）.Compared with the model group,infarct volume percentage（35.75±2.38 vs.24.23±1.92）of the D-gal model group significantly increased（P0.01）.Abnormal pathological changes of swelling,degeneration,dissolution and leukoaraiosis were observed in ischemic area neurons of the model group.The pathological changes of the D-gal model group was more serious than the model group.Conclusions The model can simulate the human brain ischemia and it was an ideal animal model for the pathogenesis of brain ischemia.