基于HIF-1α/VEGF轴研究电针对大鼠术后认知功能障碍的影响及作用机制

The Effect and Mechanism of Electroacupuncture on Postoperative Cognitive Dysfunction of Rat Based on HIF-1α/VEGF Axis

目的基于缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)轴研究电针对大鼠术后认知功能障碍(POCD)的影响及作用机制。方法选择18个月龄的雄性SD大鼠30只,随机分为对照组、术后认知功能障碍组(POCD组)、电针组,每组各10只,POCD组和电针组3%七氟醚麻醉下进行剖腹探查,电针组在手术前30 min及手术后1~7 d每日给予电针干预。采用Morris水迷宫检测认知功能指标逃避潜伏期、穿越平台次数,采用western blot检测核因子-κB(NF-κB)、B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)、裂解型含半胱氨酸的天冬氨酸蛋白水解酶-3(Cleaved caspase-3)、HIF-1α、VEGF,采用酶联免疫吸附法检测肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β),采用TUNEL法检测细胞凋亡率。结果与对照组比较,POCD组大鼠的逃避潜伏期延长、穿越平台次数减少,海马组织中NF-κB、Bax、Cleaved caspase-3、HIF-1α、VEGF的表达水平、TNF-α、IL-1β的含量及细胞凋亡率增加,Bcl-2的表达水平降低,差异有统计学意义(P<0.05);与POCD组比较,电针组逃避潜伏期缩短、穿越平台次数增加,海马组织中NF-κB、Bax、Cleaved caspase-3、HIF-1α、VEGF的表达水平、TNF-α、IL-1β的含量及细胞凋亡率降低,Bcl-2的表达水平增加,差异有统计学意义(P<0.05)。结论电针对POCD具有改善作用,抑制HIF-1α/VEGF轴并起到抗炎、抗凋亡作用是与之相关的分子机制。

Objective To study the effect and mechanism of electroacupuncture on postoperative cognitive dysfunction(POCD)of rat based on hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)axis.Methods Thirty 18 month old male SD rats were randomly divided into control group,POCD group,electroacupuncture group,ten rats in each group.Laparotomy was performed in POCD group and electroacupuncture group under 3%sevoflurane anesthesia.The electroacupuncture group was given electroacupuncture intervention 30 minutes before and 1-7 days after operation.Morris water maze was used to detect the cognitive function index escape latency and crossing platform times.The expression of NF-κB,Bcl-2,Bax,cleaved caspase-3,HIF-1αand VEGF were detected by Western blot.The contents of TNF-αand IL-1βwere detected by enzyme-linked immunosorbent assay.Apoptosis rate was detected by TUNEL.Results Compared with the control group,rats in the POCD group had prolonged escape latency and reduced the number of crossing platforms.The expression levels of NF-κB,Bax,Cleaved caspase-3,HIF-1α,VEGF,and the levels of TNF-αand IL-1βin the hippocampus The content and apoptosis rate increased,and the expression level of Bcl-2 decreased,and the difference was statistically significant(P<0.05).Compared with the POCD group,the EA group had shorter escape latency and increased the number of crossing platforms.NF-κB,NF-κB,The expression level of Bax,Cleaved caspase-3,HIF-1α,VEGF,the content of TNF-α,IL-1β,and the rate of apoptosis decreased,and the expression level of Bcl-2 increased,and the difference was statistically significant(P<0.05).Conclusion Electroacupuncture can improve POCD,and inhibiting HIF-1α/VEGF axis and having anti-inflammatory and anti-apoptotic effects are related molecular mechanisms.