胡椒碱调节AC/PKA/CREB信号通路对脑梗死大鼠海马神经元凋亡的影响  

Effect of piperine on AC/PKA/CREB signaling pathway on hippocampal neuron apoptosis in rats with cerebral infarction

作　　者：李德炎 黄宗文 吴亚丹 陈秀红 LI Deyan;HUANG Zongwen;WU Yadan;CHEN Xiuhong(Traditional Chinese Medicine,Geriatric Hospital of Hainan,Haikou 571100,China;Traditional Chinese Medicine,the First Affiliated Hospital of Hainan Medi-cal University,Haikou 570102,China;Physical Examination Center,Geriatric Hospital of Hainan,Haikou 571100,China)

机构地区：[1]海南省老年病医院中医科,海口571100 [2]海南医科大学第一附属医院中医科,海口570102 [3]海南省老年病医院体检中心,海口571100

出　　处：《中国免疫学杂志》2024年第12期2537-2542,共6页Chinese Journal of Immunology

基　　金：2020年海南省自然科学基金面上项目(820RC778)。

摘　　要：目的:探讨胡椒碱(PIP)对脑梗死大鼠神经损伤的影响及机制。方法:采用改良线栓法制备脑梗死大鼠模型,将大鼠分为Sham组、Model组、PIP组(PIP组,20 mg/kg PIP)、PIP^(+)PKA抑制剂组(PIP^(+)H-89组,20 mg/kg PIP^(+)5 mg/kg H-89)。各组大鼠进行神经功能缺损评分,观察脑梗死体积、神经元损伤及神经元凋亡,检测海马组织cAMP、IL-1β和IL-6水平及GFAP、NSE、AC6、PKA、p-CREB、CREB、BDNF蛋白表达。结果:与Sham组比较,Model组出现大面积脑梗死,脑梗死体积、神经功能缺损评分、神经元凋亡率、海马组织IL-6、IL-1β水平、GFAP阳性细胞数、NSE蛋白阳性表达率升高,海马组织尼氏体数目、cAMP及AC6、PKA、p-CREB、BDNF蛋白表达水平降低(P<0.05);与Model组比较,PIP组脑梗死体积、神经功能缺损评分、神经元凋亡率、海马组织IL-6、IL-1β水平、GFAP阳性细胞数、NSE蛋白阳性表达率降低,海马组织尼氏体数目、cAMP及AC6、PKA、pCREB、BDNF蛋白表达水平升高(P<0.05);胡椒碱改善脑梗死大鼠神经损伤的作用可被H-89逆转。结论:PIP可通过激活AC/PKA/CREB信号通路抑制海马神经元凋亡,改善脑梗死引起的神经损伤。Objective:To investigate the effect and of piperine(PIP)on nerve injury in rats with cerebral infarction.Meth⁃ods:The rat model of cerebral infarction was prepared by modified thread embolism method.The rats were divided into Sham group,Model group,piperine group(PIP group,20 mg/kg piperine),piperine^(+)PKA inhibitor group(PIP^(+)H-89 group,20 mg/kg PIP^(+)5 mg/kg H-89).The rats were scored for neurological impairment,the volume of cerebral infarction,neuronal damage and neuronal apoptosis were observed,and the levels of cAMP,IL-1βand IL-6 in hippocampus and the protein expressions of GFAP,NSE,AC6,PKA,p-CREB,CREB and BDNF were detected.Results:Compared with Sham group,Model group had large cerebral infarction,cerebral infarction volume,the neurological deficit score,neuronal apoptosis rate,the levels of IL-6 and IL-1βin hippocampus,and number of GFAP positive cells,the positive expression rates of NSE protein increased,the number of Nissl bodies,and the expressions of cAMP,AC6,PKA,p-CREB and BDNF proteins in hippocampus decreased(P<0.05);compared with Model group,cerebral infarction volume,the neurological deficit score,neuronal apoptosis rate,the levels of IL-6 and IL-1βin hippocampus,and number of GFAP positive cells,the positive expression rates of NSE protein in the PIP group decreased,the number of Nissl bodies,and the expressions of cAMP,AC6,PKA,p-CREB and BDNF proteins in hippocampus increased(P<0.05);the effect of piperine in improving nerve injury in rats with cerebral infarction was able to be reversed by H-89.Conclusion:PIP can inhibit the apoptosis of hippocampal neurons,and improve the neural injury induced by cerebral infarction by activating AC/PKA/CREB signal pathway.

关 键 词：胡椒碱 脑梗死 AC/PKA/CREB信号通路 神经元 

分 类 号：R743.33[医药卫生—神经病学与精神病学]