大蒜素对丙泊酚麻醉所致老年大鼠认知功能障碍的影响

Effect of allicin on cognitive dysfunction induced by propofol anesthesia in aged rats

关键词:  大蒜素  丙泊酚  认知功能  海马  氧化应激  炎症

Key words:  alicin  propofol  cognitive function  hippocampus  oxidative stress  inflammation

摘要:

[目的] 研究大蒜素对丙泊酚麻醉所致老年大鼠认知功能障碍的影响及其机制。[方法] 将120只20月龄老年SD大鼠随机平均分为正常对照组、模型组、吡拉西坦组(500 mg/kg)和大蒜素低、中、高剂量组(5、10、20 mg/kg)；除正常对照组外，其余各组均100 mg/kg腹腔注射丙泊酚麻醉，造模后各组分别连续1次/d腹腔注射给药7 d(正常对照组和模型组给予生理盐水)。通过Morris水迷宫实验评测各组大鼠认知功能；苏木精-尹红(HE)、原位末端标记(TUNEL)染色法行海马CA1区神经元病理性损伤和神经元凋亡检查；生化分析法检测海马区超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性和丙二醛(MDA)含量，ELISA法检测炎症细胞因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)]含量；蛋白质印迹法(Western blot)检测海马区核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)、核因子-κB(NF-κB)蛋白表达。[结果] 与模型组比较，吡拉西坦组和大蒜素中、高剂量组大鼠逃逸潜伏期缩短、穿越平台次数增加(P<0.05或P<0.01)，海马CA1区神经元病变明显好转，神经元凋亡数量明显减少、凋亡指数(AI)显著降低(P<0.05或P<0.01)，SOD、CAT活性显著升高且MDA、TNF-α、IL-1β、IL-6含量显著降低(P<0.01)；Nrf2、HO-1表达显著上调且NF-κB表达显著下调(P<0.01)。与吡拉西坦组比较，大蒜素高剂量组大鼠逃逸潜伏期缩短、穿越平台次数增加(P<0.05)，AI显著降低(P<0.01)，SOD活性显著升高且MDA、TNF-α含量显著降低(P<0.05或P<0.01)；Nrf2、HO-1表达显著上调且NF-κB表达显著下调(P<0.05或P<0.01)。[结论] 大蒜素对丙泊酚麻醉所致老年大鼠认知功能障碍具有改善作用，其机制可能与激活Nrf2/HO-1通路、抑制NF-κB蛋白表达进而抑制海马CA1区神经元凋亡、氧化应激和炎症反应有关。

Abstract:

[Objective] To investigate the effect of allicin on the cognitive dysfunction induced by propofol anesthesia in aged rats and its mechanism.[Methods] The 120 twenty-months old SD rats were randomly divided into normal control group,model group,piracetam group (500 mg/kg) and allicin low,medium,high dose groups (5,10,20 mg/kg). Except for normal control group,all the other groups were given propofol at 100 mg/kg for anesthesia by intraperitoneal injection,and the drugs were given for 7 days in each group after modeling (the rats in normal control group and model group were given normal saline). The cognitive function of the rats in each group were evaluated by Morris water maze experiment,the pathological damage of hippocampal CA1 area neurons was detected by HE staining and the neuronal apoptosis was observed by TUNEL staining. The activity of superoxide dismutase (SOD),catalase (CAT) and the content of malondialdehyde (MDA) in lung tissue were detected by biochemical analysis method. The content of inflammatory cytokines including tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),interleukin-6 (IL-6) were detected by ELISA method. The expression of nuclear factor E2 correlation factor 2 (Nrf2),Heme oxygenase-1 (HO-1),nuclear factor-κB (NF-κB) were determined by Western blot.[Results] Compared with model group,the escape latency of the rats in piracetam group and allicin medium,high dose groups were shorter and the number of crossing platforms was increased (P<0.05 or P<0.01). The neuronal pathology in hippocampal CA1 area improved significantly,the number of neuronal apoptosis was significantly reduced,and the apoptosis index (AI) was significantly reduced (P<0.05 or P<0.01). The activity of SOD,CAT were increased and the content of MDA,TNF-α,IL-1β,IL-6 were decreased(P<0.01). The expression of Nrf2,HO-1 were up-regulated and the NF-κB was down-regulated (P<0.01). Compared with piracetam group,the escape latency of the rats in allicin high dose groups was shorter and the number of crossing platforms was increased (P<0.05). The AI was significantly reduced (P<0.01). The activity of SOD was increased and the content of MDA,TNF-α were decreased(P<0.05 or P<0.01). The expression of Nrf2, HO-1 were up-regulated and the NF-κB was down-regulated (P<0.05 or P<0.01).[Conclusion] Allicin can improve the cognitive dysfunction induced by propofol anesthesia in aged rats,which mechanism may be related to activating the Nrf2/HO-1 pathway and inhibiting the expression of NF-κB protein,and then inhibiting neuronal apoptosis,oxidation,inflammatory in hippocampal CA1 area.