局部脑低温与烟酰胺磷酸核糖基转移酶协同保护大鼠脑缺血再灌注损伤  

Local brain hypothermia and nicotinamide phosphoribosyltransferase synergistically protect cerebral ischemia-reperfusion injury in rats

作　　者：何小夺 段云霞[1] 师敬飞[1] 吴迪[1] 丁玉川[1] He Xiaoduo;Duan Yunxia;Shi Jingfei;Wu Di;Ding Yuchuan(China-America Institute of Neuroscience,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院中美神经科学研究所,北京100053

出　　处：《国际脑血管病杂志》2019年第4期267-272,共6页International Journal of Cerebrovascular Diseases

基　　金：国家自然科学基金(81500997,81871022);北京市医管局青苗项目(QML20170802).

摘　　要：目的探讨局部低温联合烟酰胺磷酸核糖基转移酶(nicotinamide phosphoribosyltransferase,NAMPT)对大鼠脑缺血再灌注损伤的神经保护作用及其机制。方法Sprague-Dawley大鼠54只随机分为假手术组、模型组、NAMPT组、局部低温组和联合治疗组(NAMPT+局部低温)。采用线栓法制备大鼠局灶性脑缺血再灌注模型。在大鼠脑缺血2 h再灌注24 h后利用2,3,5-氯化三苯基四氮唑染色评估梗死和脑水肿体积,伊文斯蓝染色评估血脑屏障损伤程度,12分量表评估神经功能缺损。结果局部低温组、NAMPT组和联合治疗组梗死体积均显著小于模型组(P均<0.05);联合治疗组梗死体积显著小于NAMPT组(P<0.05);联合治疗组梗死体积小于局部低温组,但未达到统计学意义。局部低温组、NAMPT组和联合治疗组神经功能评分均显著低于模型组(P均<0.05);联合治疗组评分显著低于NAMPT组和局部低温组(P均<0.05)。局部低温组、NAMPT组和联合治疗组伊文斯蓝渗漏均少于模型组(P均<0.05),但各治疗组间差异无统计学意义。结论NAMPT和局部低温联合治疗对脑缺血再灌注损伤显示出更好的神经保护作用,提示联合治疗具有临床转化前景。Objective To investigate the neuroprotective effect and its mechanism of local hypothermia combined with nicotinamide phosphoribosyltransferase (NAMPT) on cerebral ischemia-reperfusion injury in rats. Methods Fifty-four Sprague-Dawley rats were randomly divided into sham operation group, model group, NAMPT group, local hypothermia group, and combined treatment group (NAMPT+ local hypothermia). A rat model of local cerebral ischemia-reperfusion was induced by suture method. Infarct volume and cerebral edema volume were assessed by 2, 3, 5-triphenyltetrazolium chloride staining after 2 h cerebral ischemia and 24 h reperfusion in rats. Evans blue staining was used to assess the extent of blood-brain barrier damage, and a 12-point scale was used to assess neurological deficits. Results The infarct volume in the local hypothermia group, NAMPT group, and combination treatment group was significantly lower than that in the model group (all P<0.05). The infarct volume in the combination treatment group was significantly lower than that in the NAMPT group (P<0.05). The infarct volume in the combination treatment group was lower than that in the local hypothermia group, but it did not reach statistical significance. The neurological function scores of the local hypothermia group, NAMPT group, and combination treatment group were significantly lower than those of the model group (all P<0.05). The score of the combined treatment group was significantly lower than that of the NAMPT group and the local hypothermia group (all P<0.05). Evans blue leakage in the local hypothermia group, NAMPT group, and combination treatment group was lower than that in the model group (all P<0.05), but the differences between each treatment group were not statistically significant. Conclusion NAMPT and local hypothermia combination therapy showed better neuroprotective effects on cerebral ischemia-reperfusion injury, suggesting that the combination therapy had clinical transformation prospects.

关 键 词：脑缺血 再灌注损伤 烟酰胺磷酸核糖基转移酶 低温 人工 神经保护 疾病模型 动物 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]