甘草甜素通过调节PI3K/Akt/GSK3β信号通路对脑卒中偏瘫痉挛状态大鼠的痉挛状态的影响  

Effect of glycyrrhizin on the spasticity of hemiplegic spasticity in stroke rats by regulating the PI3K/Akt/GSK3βsignaling pathway

作　　者：胡斌[1] 柴德君 HU Bin;CHAI De-jun(Department of Rehabilitation Medicine,The Second Affiliated Hospital of Qiqihar MedicalCollege,Qiqihar 161000,Heilongjiang Province,China)

机构地区：[1]齐齐哈尔医学院附属第二医院康复医学科,黑龙江齐齐哈尔161000

出　　处：《中国临床药理学杂志》2024年第12期1779-1783,共5页The Chinese Journal of Clinical Pharmacology

基　　金：黑龙江省卫生健康委科研课题基金资助项目(20212020010020)。

摘　　要：目的研究甘草甜素(GA)通过调节磷酸肌苷3-激酶(PI3K)/蛋白激酶B(Akt)/糖原合成酶激酶3β(GSK3β)信号通路对脑卒中偏瘫痉挛状态大鼠神经行为学的影响。方法用大脑中动脉闭塞(MCAO)建立脑卒中后痉挛(PSS)大鼠模型。将大鼠分为对照组、假手术组、模型组、低剂量甘草甜素组、高剂量甘草甜素组、巴氯芬组。模型组、假手术组和对照组大鼠每天灌胃等量的0.9%NaCl,高剂量甘草甜素组每天灌胃给予10.8 g·kg^(-1)甘草甜素,低剂量甘草甜素组每天灌胃给予5.4 g·kg^(-1)甘草甜素,巴氯芬组每天灌胃5.4 mg·kg^(-1)巴氯芬,连续4周。用改良Ashworth量表评定肌肉张力,用2,3,5-氯化三苯基四氮唑(TTC)染色法分析脑组织中脑梗死体积,用尼氏染色法和透射电镜观察GA对大鼠脑缺血再灌注损伤后神经元损伤的保护作用,用免疫组化染色法检测脑梗死和脑干周围脑组织中磷酸化PI3K(p-PI3K)、磷酸化Akt(p-Akt)和磷酸化GSK3β(p-GSK3β)的表达水平。结果假手术组、模型组、低剂量甘草甜素组、高剂量甘草甜素组和巴氯芬组大鼠脑梗死体积分别为0、(34.23±1.21)%、(24.12±1.03)%、(18.26±1.08)%和(26.38±1.35)%。对照组、假手术组、模型组、低剂量甘草甜素组、高剂量甘草甜素组的尼氏小体含量分别为(126.23±8.13)%、(131.14±9.62)%、(52.21±6.11)%、(84.29±6.17)%和(112.24±8.21)%。在4周时,假手术组、模型组、低剂量甘草甜素组、高剂量甘草甜素组和巴氯芬组的p-PI3K在脑梗死周围的脑组织中的表达分别为5.45±0.44、4.89±0.34、5.54±0.42、20.59±1.35、25.34±1.46和6.47±0.45,p-PI3K在脑干周围的脑组织中的表达分别为14.47±1.48、10.82±1.24、15.39±1.45、13.51±1.32、25.55±1.49和8.84±0.74,p-Akt在脑梗死周围的脑组织中的表达分别为6.47±0.41、6.18±0.32、5.58±0.51、19.54±1.48、28.56±1.48和14.39±1.56,p-Akt在脑干周围的脑组织中的表达分别为6.45±1.41、8.09±Objective To investigate the effect of glycyrrhizin(GA)on the spasticity of hemiplegic spasticity in stroke rats by regulating the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/glycogen synthase kinase 3β(GSK3β)signaling pathway.Methods A rat model of post-stroke spasm(PSS)was established by middle cerebral artery occlusion(MCAO).Rats were divided into control group,sham operation group,model group,GA-L group,GA-H group and baclofen group.Rats in the model group,sham operation group and control group were intragastrically administered with the same amount of 0.9%NaCl every day,GA-H group was given 10.8 g·kg^(-1)GA by gavage daily,GA-L group was given 5.4 g·kg^(-1)GA by gavage every day,baclofen group was intragastrically administered with 5.4 mg·kg^(-1)baclofen every day for 4 weeks.Muscle tone was assessed by modified Ashworth scale.The volume of cerebral infarction was analyzed by 2,3,5-triphenyltetrazolium chloride(TTC)staining.The protective effect of GA on neuronal injury after cerebral ischemiareperfusion injury was observed by Nissl staining and transmission electron microscopy.The expression levels of phosphorylated PI3K(p-PI3K),phosphorylated Akt(p-Akt)and phosphorylated GSK3β(p-GSK3β)in cerebral infarction and peripheral brain stem were detected by immunohistochemical staining.Results The volume of cerebral infarction in sham operation group,model group,GA-L group,GA-H group and baclofen group were 0,(34.23±1.21)%,(24.12±1.03)%,(18.26±1.08)%and(26.38±1.35)%,respectively.The contents of Nissl bodies in control group,sham operation group,model group,GA-L group,GA-H group were(126.23±8.13)%,(131.14±9.62)%,(52.21±6.11)%,(84.29±6.17)%and(112.24±8.21)%,respectively.At 4 weeks,the expressions of p-PI3 K in sham operation group,model group,GA-L group,GA-H group and baclofen group in brain tissue surrounding cerebral infarction were 5.45±0.44,4.89±0.34,5.54±0.42,20.59±1.35,25,34±1.46 and 6.47±0.45;the expression of p-PI3K in the brain tissues around brain stem were14.47±1.48,10.82�

关 键 词：甘草甜素 脑卒中痉挛 脑缺血再灌注损伤 磷酸肌苷3-激酶/蛋白激酶B/糖原合成酶激酶3β信号通路 神经行为学 

分 类 号：R28[医药卫生—中药学]