cAMP/PKA⁃pCREB信号通路在早期康复训练改善脑卒中患者神经功能中的作用

Role of cAMP/PKA⁃pCREB signaling pathway in early rehabilitation training to improve neurological function in stroke patients

目的研究环腺苷酸(cAMP)/蛋白激酶A(PKA)⁃磷酸化cAMP反应元件结合蛋白(pCREB)信号通路在早期康复训练改善脑卒中患者神经功能中的作用。方法将缺血性脑卒中患者分为进行早期康复训练的观察组、常规康复训练的对照组,干预前及干预后1周时采用简易智能精神状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)、Fugl⁃Meyer运动功能量表(FMA)、Berg平衡量表(BBS)评价神经功能,检测血清cAMP、PKA、肿瘤坏死因子⁃α(TNF⁃α)、白介素⁃1β(IL⁃1β)、白介素⁃6(IL⁃6)、丙二醛(MDA)、超氧化物歧化酶(SOD)、总抗氧化力(TAOC)、B淋巴细胞瘤⁃2(Bcl⁃2)、Bcl⁃2相关X蛋白(Bax)、含半胱氨酸的天冬氨酸蛋白水解酶⁃3(Caspase⁃3)含量及外周血pCREB表达水平。结果两组干预后的MMSE、MoCA、FMA、BBS评分均高于组内干预前且观察组高于对照组,差异有统计学意义(t=5.099、3.778、2.658、3.502,P<0.05),血清cAMP、PKA及外周血pCREB表达水平均高于组内干预前且观察组高于对照组,差异有统计学意义(t=3.858、3.958、8.815,P<0.05),血清TNF⁃α、IL⁃1β、IL⁃6含量均低于组内干预前且观察组低于对照组,差异有统计学意义(t=10.338、9.395、5.936,P<0.05),血清MDA含量低于组内干预前且观察组低于对照组、SOD及TAOC含量高于组内干预前且观察组高于对照组,差异有统计学意义(t=5.272、3.714、4.753,P<0.05),血清Bax及Caspase⁃3均低于组内干预前且观察组低于对照组,Bcl⁃2含量高于组内干预前且观察组高于对照组,差异有统计学意义(t=18.669、11.346、9.903,P<0.05)。结论早期康复训练改善脑卒中患者神经功能的作用与激活cAMP/PKA⁃pCREB信号通路并抑制炎症反应、氧化应激、细胞凋亡有关。

Objective To investigate the role of cyclic adenylate(cAMP)/protein kinase A(PKA)⁃phosphorylated cAMP response element binding protein(pCREB)signaling pathway in early rehabili⁃tation training to improve neurological function in stroke patients.Methods Patients with ischemic stroke were divided into the observation group that received early rehabilitation training and the control group that re⁃ceived routine rehabilitation training.Before and 1 week after the intervention,neurological function was as⁃sessed by Mini mental state examination(MMSE),Montreal cognitive assessment(MoCA),Fogl⁃Meyer as⁃sessment(FMA),Motion Function Scale,Berg Balance Scale(BBS).cAMP,PKA,tumor necrosis factor⁃α(TNF⁃α),interleukin⁃1β(IL⁃1β),interleukin⁃6(IL⁃6),malondialdehyde(MDA),superoxide dismutase(SOD),total antioxidant force(TAOC),B lymphocystoma⁃2(Bcl⁃2),Bcl⁃2 associated X protein(Bax),cysteine⁃containing aspartate proteolylase⁃3(Caspase⁃3)contents in Serum and pCREB expression levels in pe⁃ripheral blood were measured.Results The MMSE,MoCA,FMA,BBS score of two groups after interven⁃tion were higher than those before intervention and the observation group was higher than the control group,the difference was statistically significant(t=5.099,3.778,2.658,3.502,P<0.05),serum cAMP,PKA con⁃tents,and peripheral pCREB expression levels were higher than those before intervention and the observation group was higher than the control group,the difference was statistically significant(t=3.858,3.958,8.815,P<0.05).Serum TNF⁃α,IL⁃1β,IL⁃6 levels were lower than those before intervention and the observation group was lower than the control group,the difference was statistically significant(t=10.338,9.395,5.936,P<0.05).Serum MDA level was lower than that before intervention and the observation group was lower than the control group,SOD,TAOC levels were higher than those before intervention and the observation group was higher than the control group,the difference was statistically significant(t=5.272,3.714,4.753,P<0.05).Serum Bax,Caspase⁃3 levels were lower than those before intervention and the observation group was lower than the control group,serum Bcl⁃2 level was higher than that before intervention and the observation group was higher than the control group,the difference was statistically significant(t=18.669,11.346,9.903,P<0.05).Conclusion Effect of early rehabilitation training on improving neurological function in stroke patients is related to the activation of cAMP/PKA⁃pCREB signaling pathway and the inhibition of in⁃flammatory response,oxidative stress,and cell apoptosis.