摘要
目的 探讨姜黄素对七氟烷致老年大鼠认知功能障碍及海马神经细胞凋亡的改善作用及可能的作用机制。方法 选取48只SD雄性大鼠建立术后认知功能障碍(postoperative cognitive dysfunction,POCD)模型,将建模成功的大鼠随机分为模型组(12只)、姜黄素低剂量组(12只)和姜黄素高剂量组(12只),另设对照组(12只)。姜黄素低、中、高剂量组分别用50、150、300 mg·kg^(-1)姜黄素混悬液(用生理盐水配制)灌胃,对照组及模型组用等量生理盐水灌胃,连续处理4周。用Morris水迷宫实验评定各组大鼠认知功能损伤程度及改善情况;用ELISA法检测各组大鼠血清肿瘤坏死因子-α(tumour necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-6(interleukin-6,IL-6)的水平;用HE染色观察各组大鼠海马组织CA1区的病理变化;用TUNEL法检测大鼠海马组织CA1区神经细胞凋亡情况;分别用RT-qPCR和Western blot检测海马组织中磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)、蛋白激酶B(protein kinase B,AKT)和糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK3β)mRNA和蛋白的表达情况。结果 与模型组比较,3个给药组大鼠Morris水迷宫逃避潜伏期、TNF-α、IL-1β、IL-6、海马组织细胞凋亡率、GSK3β mRNA和p-GSK3β蛋白的表达水平降低,跨台次数及PI3K、AKT mRNA和p-AKT蛋白的表达水平升高(P<0.05)。与低剂量组比较,姜黄素中、高剂量组上述指标均明显降低,以高剂量组的变化最明显(P<0.05)。结论 姜黄素能够改善七氟烷所致POCD大鼠认知功能障碍,减轻炎症反应,降低海马神经细胞凋亡率,可能是通过激活PI3K/AKT/GSK3β信号通路发挥作用的。
Objective To investigate the improvement effect of curcumin on cognitive impairment and hippocampal neuron apoptosis by sevoflurane in aged rats and its possible mechanism.Methods 48 SD rats were selected to establish the model of cognitive impairment(postoperative cognitive dysfunction,POCD).The successfully modeled rats were randomly divided into model group,curcumin low,medium and high dose groups,and control group,12 rats in each group.Curcumin low(50 mg·kg^(-1)),medium(150 mg·kg^(-1))and high dose(300 mg·kg^(-1))groups were given curcumin in the form of suspension(prepared with normal saline)by gavage respectively.The control group and model group were given the same amount of normal saline for 4 weeks.Morris water maze test was used to evaluate the degree of cognitive impairment and improvement of rats in each group.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)were detected by ELISA.The pathological changes of hippocampal CA1 area of rats were observed by HE staining.The neuronal apoptosis of rat hippocampal CA1 area was detected by TUNEL.The mRNA and protein expressions of phosphatidylinositol3-kinase(PI3K),protein kinase B(AKT)and glycogen synthase kinase-3β(GSK3β)in hippocampus were detected by RT qPCR and Western blot.Results Compared with the model group,the escape latency of Morris water maze and the levels of TNF-α,IL-1β,IL-6,apoptosis rate of hippocampal tissue,GSK3βmRNA and p-GSK3βprotein expression of curcumin groups were decreased,and the numbers of platform,PI3K,AKT mRNA and p-AKT protein expression were increased in low,medium and high dose curcumin groups(P<0.05).Compared with the low dose curcumin group,the escape latency of Morris water maze and the levels of TNF-α,IL-1β,IL-6,apoptosis rate of hippocampal tissue,GSK3βmRNA and p-GSK3βprotein expression were decreased,and the numbers of platform,PI3K,AKT mRNA and p-AKT protein expression were increased in medium and high dose curcumin groups(P<0.05).Compared with the medium dose curcumin group,the indexes were increased more significantly(P<0.05).Conclusion Curcumin can improve the cognitive impairment,reduce the inflammatory response and apoptosis rate of hippocampal neurons in POCD rats induced by sevoflurane,possibly by activating PI3K/AKT/GSK3βsignaling pathways.
作者
李小娜
樊少卿
赵二贤
许宏侠
LI Xiaona;FAN Shaoqing;ZHAO Erxian;XU Hongxia(Daytime Operation Room,the Second Affiliated Hospital of He'nan University of Traditional Chinese Medicine,Zhengzhou 450002,China;Department of Anesthesia and Perioperative Medicine,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Department of Geriatrics,the First Affiliated Hospital of He'nan University,Kaifeng 475000,China)
出处
《西北药学杂志》
CAS
2023年第3期91-97,共7页
Northwest Pharmaceutical Journal
基金
2019年河南省医学科技攻关计划联合共建项目(编号:LHGJ20190505)。
