转化生长因子β1通过上调海马脑源性神经营养因子改善小鼠围术期神经认知障碍  

Activation of transforming growth factor β1 improves hippocampal perioperative neurocognitive disorders in mice by up-regulating brain-derived neurotrophic factor signaling pathway

作　　者：李晓[1] 何龙[1] 柳少轩 艾艳秋[1] Li Xiao;He Long;Liu Shaoxuan;Ai Yanqiu(Department of Anesthesiology,Pain and Perioperative Medicine,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院麻醉与围术期医学部,郑州450052

出　　处：《中华实验外科杂志》2023年第1期63-65,共3页Chinese Journal of Experimental Surgery

摘　　要：目的探讨转化生长因子(TGF)-β1通过上调海马脑源性神经营养因子(BDNF)来改善小鼠围术期神经认知障碍。方法老年小鼠共45只,20~22月龄,体重28~34 g,将其分为3组(n=15):假手术对照组(S组)、外科手术组(O组)、外科手术+小鼠重组TGF-β1(O+T组)。S组仅行戊巴比妥麻醉,不行外科手术操作;O组和O+T组小鼠在戊巴比妥麻醉下行剖腹探查术,术后即刻、24、48、72 h分别腹腔注射重组TGF-β110 mg/kg。术后第7天行Y迷宫测试;蛋白质印迹法(Western blot)检测海马TGF-β1、TGF-β2、离子钙结合衔接分子1(Iba-1)、肿瘤坏死因子-α(TNF-α)、磷酸化酪氨酸激酶受体B(p-TrkB)、酪氨酸激酶受体B(TrkB)、BDNF的蛋白表达水平。采用单因素方差分析(ANOVA)以评估组间差异。结果O组术后第7天,进入新异臂次数和新异臂停留时间低于S组[(5.500±2.302)次比(18.900±3.912)次、(30.700±10.402)s比(103.500±28.745)s,P<0.01],海马TGF-β1表达量低于S组(0.376±0.058比0.720±0.187,P<0.01),Iba-1和TNF-α蛋白表达量水平高于S组(0.233±0.065比0.089±0.012、0.741±0.149比0.264±0.203,P<0.01);O+T组术后第7天进入进入新臂的次数和停留新臂时间高于O组[(12.900±2.302)次比(5.500±2.302)次、(74.000±7.021)s比(30.700±10.402)s,P<0.01],海马p-TrkB和BDNF表达量高于O组(0.761±0.183比0.323±0.090、0.843±0.174比0.551±0.076,P<0.01),Iba-1和TNF-α表达量低于O组(0.087±0.014比0.233±0.065、0.176±0.149比0.741±0.149,P<0.01)。结论TGF-β1治疗可减轻小鼠术后认知功能障碍及海马神经炎性反应,其作用机制和上调BDNF信号通路相关。Objective To investigate the effects of hippocampal transforming growth factor(TGF)-β1 on perioperative neurocognitive disorders in mice.Methods A total of 45 aged mice,20-22 months old,weighing 28-34 g,were divided into 3 groups(n=15):Sham operation control group(group S),surgical operation group(group O),recombinant mouse TGF-β1(group O+T).Group S only received pentobarbital anesthesia.The mice in group O received surgical operation,and those in group O+T received surgery,followed by intraperitoneal injection(immediately,24 h,48 h,and 72 h after surgery)of TGF-β110 mg/kg,respectively.Y maze tests were performed on the 7th day after the operation.At 7th day after the surgical operation,the hippocampal protein levels of TGF-β1,TGF-β2,ionized calcium-binding adapter molecule 1(Iba-1),tumor necrosis factor-α(TNF-α),phosphorylated tropomyosin receptor kinase B(p-TrkB),tropomyosin receptor kinase B(TrkB)and brain-derived neurotrophic factor(BDNF)were analyzed by Western blotting.The data were analyzed using the one-way analysis of variance(ANOVA).Results Compared with group S,the escape latency was extended in group O on the 7th day after surgery,platform crossing times(5.500±2.302 vs.18.900±3.912,P<0.01)and time spent in the target quadrant(30.700±10.402 s vs.103.500±28.745 s,P<0.01)were decreased,and the hippocampal protein expression of TGF-β1(0.376±0.058 vs.0.720±0.187,P<0.01)was diminished,whereas the levels of Iba-1(0.233±0.065 vs.0.089±0.012,P<0.05)and TNF-α(0.741±0.149 vs.0.264±0.203,P<0.01)were extensively increased.Compared with group O,the escape latency was shortened in group O+T from the 7th day after surgery,platform crossing times(12.900±2.302 vs.5.500±2.302,P<0.01)and time spent in the target quadrant[(74.000±7.021)s vs.(30.700±10.402)s,P<0.01]were improved,and the hippocampal protein expression of p-TrkB(0.761±0.183 vs.0.323±0.090,P<0.05)and BDNF(0.843±0.174 vs.0.551±0.076,P<0.05)was raised,whereas the expression of Iba-1(0.087±0.014 vs.0.233±0.065,P<0.01)and TNF-α(0.176

关 键 词：转化生长因子Β1 围术期神经认知障碍 脑源性神经营养因子 肌钙蛋白受体激酶B 神经炎性反应 

分 类 号：R619[医药卫生—外科学]