摘要
目的 研究川陈皮素是否可通过核苷酸结合寡聚化结构样受体家族pyrin结构域蛋白3(NLRP3)影响七氟烷麻醉后大鼠认知障碍。方法 将30只雄性SD大鼠随机分为A、B、C三组,其中A、B组分别使用川陈皮素(100 mg/kg)及生理盐水(0.1 mL/10 g)灌胃6周,后行七氟烷麻醉与腹腔探查手术操作,C组为对照组,生理盐水(0.1 mL/10 g)灌胃6周,不做麻醉与腹腔探查手术处理,3组大鼠饲养条件一致。采用Morris水迷宫实验检测大鼠学习记忆能力,酶联免疫吸附法(ELISA)检测大鼠外周血神经功能损伤标志神经组织蛋白(S100β)水平,比色法检测大鼠脑海马组织氧化应激反应指标水平,包括超氧化物歧化酶(SOD)活性、过氧化氢(H2O2)以及丙二醛(MDA)。免疫印迹法(Western blot)检测大鼠脑海马组织NLRP3炎症小体相关蛋白,包括NLRP3、凋亡相关斑点样蛋白(ASC)、效应分子半胱氨酸蛋白酶-1(caspase-1)水平。结果 与C组相比,术后7 d,A组和B组大鼠Morris水迷宫实验中逃避潜伏期及路径显著延长,穿越平台次数显著减少(P<0.05),外周血S100β水平显著升高(P<0.05),海马组织内氧化应激指标GSH、SOD活性显著降低(P<0.05),H2O2及MDA水平显著升高(P<0.05),NLRP3炎症小体相关蛋白NLRP3、ASC以及Caspase蛋白表达水平显著升高(P<0.05)。与B组相比,A组大鼠Morris水迷宫实验中逃避潜伏期及路径显著减少、穿越平台次数显著增加(P<0.05),外周血S100β水平、海马组织氧化应激指标H2O2、MDA水平及NLRP3炎症小体相关蛋白水平均较显著降低(P<0.05);海马组织内氧化应激指标GSH、SOD活性显著升高(P<0.05)。结论 川陈皮素可能通过抑制NLRP3活性,降低麻醉后大鼠海马组织内氧化应激水平,发挥脑保护功效,降低七氟烷麻醉后的认知障碍。
Objective To study the effects of nobiletin on sevoflurane anesthesia-induced cognitive impairment in rats through regulating the activation of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3(NLRP3). Methods Thirty male SD rats were randomly divided into three groups:A,B,and C. Groups A and B were given chuanmenetin(100 mg/kg)and normal saline(0.1 mL/10 g)by gavage for 6 weeks,respectively. Sevoflurane anesthesia and abdominal exploration operation were performed. Group C was the control group,and normal saline(0.1 mL/10 g)was administered by gavage for 6 weeks. No anesthesia and abdominal exploration operation were performed. The three groups of rats were kept in the same conditions. Morris water maze test was used to detect the learning and memory ability of rats,enzyme-linked immunosorbent assay(ELISA)to detect the level of neuronal tissue protein(S100β),a marker of peripheral nerve function damage in rats,and colorimetric method to detect the oxidative stress response of rat hippocampus tissue Indicator levels,including superoxide dismutase(SOD)activity,hydrogen peroxide(H2O2),and malondialdehyde(MDA).Western blot was used to detect the levels of NLRP3 inflammasome-related proteins in rat hippocampus,including NLRP3,apoptosis-associated speck-like protein(ASC),and effector molecule cysteine protease-1(caspase-1). Results Compared with group C,the escape latency and path of rats in group A and group B in Morris water maze test were significantly prolonged,the number of crossing platforms was significantly reduced(P<0.05),and the level of S100β in peripheral blood was significantly increased(P<0.05). The activities of oxidative stress indicators GSH and SOD in the hippocampus were significantly decreased(P<0.05),the levels of H2O2and MDA were significantly increased(P<0.05),and the expression levels of NLRP3 inflammasome-related proteins NLRP3,ASC and Caspase proteins were significantly increased(P<0.05). Significantly increased(P<0.05). Compared with group B,in the Morris water maze test,the escape latency and path of rats in group A were significantly reduced,and the number of crossing platforms was significantly increased(P<0.05),the levels of S100β in peripheral blood,oxidative stress indexes H2O2and MDA in hippocampus,and NLRP3 inflammasome-related protein were significantly decreased(P<0.05);The levels of inflammasome-related proteins were significantly decreased(P<0.05);the activities of oxidative stress indexes GSH and SOD in hippocampus were significantly increased(P<0.05). Conclusion Nobiletin can exert cerebral protective effects and attenuate sevoflurane anesthesia-induced cognitive impairment by inhibiting NLRP3 activity and reducing oxidative stress levels in rat hippocampal tissue.
作者
陈林
杜宁
史宇平
王雨广
裴晓霞
贺钊
CHEN Lin;DU Ning;SHI Yu-ping;WANG Yu-guang;PEI Xiao-xia;HE Zhao(Department of Anesthesiology,Tangshan Second Hospital,Tangshan,Hebei Province 063016,China)
出处
《解剖学研究》
CAS
2022年第4期320-324,共5页
Anatomy Research
