CAJ | 학술논문

目的：评价外源性脂肪因子-13对大鼠脑缺血再灌注损伤的影响。方法 SPF级SD雄性大鼠58只，6～8周龄，体重250～320 g ，采用随机数字表法，将其分为7组：假手术组（S组，n＝10）、脑缺血再灌注组（I/R组，n＝10）、二甲基亚砜组（D组，n＝6）、1 nmol脂肪因子-13组（A1组，n＝6）、5 nmol脂肪因子-13组（A5组，n＝10）、5 nmol脂肪因子-13＋PI3K抑制剂LY294002组（A5＋LY组，n＝10）和10 nmol脂肪因子-13组（A10组，n＝6）。采用线栓法制备局灶性脑缺血再灌注损伤模型，A1组、A5组、A5＋LY组、A10组和D组于脑缺血前30 min侧脑室注射相应剂量的脂肪因子-13、脂肪因子-13＋LY29400210 nmol ，或等容量二甲基亚砜。于再灌注24、72 h时进行神经行为学评分（NBS评分），于再灌注24 h时处死大鼠，取脑组织，进行细胞凋亡计数，并测定磷酸化糖原合酶激酶-3β（pGSK-3β）表达。再灌注72 h时处死大鼠，确定脑梗死体积。结果与S组比较，I/R组各时点NBS评分降低，脑梗死体积增大，脑组织神经细胞凋亡计数升高，脑组织pGSK-3β表达上调（ P＜0.05或0.01）；与I/R组比较，A5组和A10组NBS评分升高，脑梗死体积减少，A5组脑组织神经细胞凋亡计数减少，脑组织pGSK-3β表达上调（ P＜0.05）；与A5组比较，A5＋LY组NBS评分降低，脑梗死体积增大，脑组织pGSK-3β表达下调（ P＜0.05）。结论外源性脂肪因子-13可减轻大鼠脑缺血再灌注损伤，其机制与激活PI3K信号通路从而促进GSK-3β失活有关。
목적：평개외원성지방인자-13대대서뇌결혈재관주손상적영향。방법 SPF급SD웅성대서58지，6～8주령，체중250～320 g ，채용수궤수자표법，장기분위7조：가수술조（S조，n＝10）、뇌결혈재관주조（I/R조，n＝10）、이갑기아풍조（D조，n＝6）、1 nmol지방인자-13조（A1조，n＝6）、5 nmol지방인자-13조（A5조，n＝10）、5 nmol지방인자-13＋PI3K억제제LY294002조（A5＋LY조，n＝10）화10 nmol지방인자-13조（A10조，n＝6）。채용선전법제비국조성뇌결혈재관주손상모형，A1조、A5조、A5＋LY조、A10조화D조우뇌결혈전30 min측뇌실주사상응제량적지방인자-13、지방인자-13＋LY29400210 nmol ，혹등용량이갑기아풍。우재관주24、72 h시진행신경행위학평분（NBS평분），우재관주24 h시처사대서，취뇌조직，진행세포조망계수，병측정린산화당원합매격매-3β（pGSK-3β）표체。재관주72 h시처사대서，학정뇌경사체적。결과여S조비교，I/R조각시점NBS평분강저，뇌경사체적증대，뇌조직신경세포조망계수승고，뇌조직pGSK-3β표체상조（ P＜0.05혹0.01）；여I/R조비교，A5조화A10조NBS평분승고，뇌경사체적감소，A5조뇌조직신경세포조망계수감소，뇌조직pGSK-3β표체상조（ P＜0.05）；여A5조비교，A5＋LY조NBS평분강저，뇌경사체적증대，뇌조직pGSK-3β표체하조（ P＜0.05）。결론외원성지방인자-13가감경대서뇌결혈재관주손상，기궤제여격활PI3K신호통로종이촉진GSK-3β실활유관。
Objective To evaluate the effect of exogenous apelin-13 on cerebral ischemia-reperfusion (I/R) injury in rats .Methods Fifty-eight male Sprague-Dawley rats ,aged 6-8 weeks ,weighing 250-320 g ,were randomly divided into 7 groups using a random number table :sham operation group (group S , n=10 ) ,I/R group (n=10) ,dimethyl sulfoxide group (group D , n=6) ,apelin-13 (1 nmol) + I/R group (group A1 , n=6) , apelin-13 (5 nmol ) + I/R group (group A5 , n=10 ) ,apelin-13 (5 nmol ) + LY294002 (PI3K inhibitor ) group (group A5 +LY , n=10) ,and apelin-13 (10 nmol) + I/R group (group A10 , n=6) .Focal cerebral ischemia was produced by introducing a nylon intraluminal suture into the cervical internal carotid artery and advancing it intracranially to block blood flow into the middle cerebral artery according to the method described by Longa et al . The corresponding dose of apelin-13 ,apelin-13+ LY294002 10 nmol ,or the equal volume of dimethyl sulfoxide was injected into the lateral cerebral ventricle in each group at 30 min before cerebral ischemia .Neurological function was assessed and scored using neurologic behavior scores (NBSs) at 24 and 72 h of reperfusion .The rats were sacrificed at 24 h of reperfusion and brains removed for detection of cell apoptosis and expression of phosphorylated-glycogen synthase kinase 3 beta (pGSK-3β) .The rats were sacrificed at 72 h of reperfusion to measure the cerebral infarct size .Results Compared with S group ,NBSs at each time point were significantly decreased ,the cerebral infarct size was enlarged ,the number of apoptotic neurons was increased ,and pGSK-3βexpression was up-regulated in group I/R ( P<0.05 or 0.01) .Compared with I/R group ,NBSs were significantly increased ,and the cerebral infarct size was decreased in A 5 and A10 groups ,and the number of apoptotic neurons was reduced ,and pGSK-3βexpression was up-regulated in group A5 ( P<0.05) .NBSs were significantly lower , the cerebral infarct size was larger ,and pGSK-3βexpression was lower in A5+LY group than in A5 group ( P<0.05) .Conclusion Exogenous Apelin-13 can attenuate cerebral I/R injury in rats and activation of the PI3K signaling pathway and enhanced inactivation of GSK-3βare involved in the mechanism .