低频脉冲电刺激抑制Notch/NF-κB通路活化改善脑卒中后吞咽障碍的研究

Study on inhibition of Notch/NF-κB pathway activation by low-frequency pulsed electrical stimulation in improving swallowing disorder after stroke

目的研究低频脉冲电刺激对脑卒中后吞咽障碍患者吞咽功能影响,以及对神经源性基因同源蛋白(Notch)/核转录因子-κB(NF-κB)信号通路的影响。方法选择2021年6月至2023年1月在河北省退役军人总医院治疗的脑卒中后吞咽障碍患者120例,其中男性58例,女性62例;年龄45~68岁,平均年龄56.82岁;病程2~8周,平均病程4.61周。随机将患者分为2组,即研究组(常规训练+脉冲电刺激)、对照组(常规训练),每组60例。两组患者均进行营养脑神经细胞、降低颅内压、控制脑水肿和改善脑组织循环等常规治疗,且均进行吞咽康复训练;研究组加用低频脉冲电刺激治疗。治疗前和治疗结束后,应用洼田饮水试验对两组患者的吞咽功能进行检测。参考《摄食、吞咽障碍康复实用技术》评价患者临床疗效。评价治疗前后美国国立卫生院卒中量表(NIHSS)评分。检测治疗前后血液组织中Notch、Hes1、p-NF-κBp65/NF-κBp65、Bax蛋白表达。结果治疗后,两组洼田饮水试验评分均降低,研究组比对照组更低[(2.23±0.64)分vs(3.02±0.81)分。P<0.01]。治疗后,研究组总有效率高于对照组患者(93.33%vs 75.00%。P<0.05)。治疗后,两组NIHSS评分均降低,研究组比对照组更低[(10.32±1.85)分vs(7.18±2.31)分。P<0.05]。治疗后,两组患者Notch、Hes1、p-NF-κBp65/NF-κBp65、Bax蛋白表达均有降低(0.86±0.09 vs 1.42±0.12、0.74±0.11 vs 1.39±0.09、0.86±0.09 vs 1.52±0.14、0.79±0.07 vs 1.52±0.10。P<0.05),且研究组Notch、Hes1、p-NF-κBp65/NF-κBp65、Bax蛋白表达低于对照组(0.86±0.09 vs 1.12±0.10、0.74±0.11 vs 1.04±0.12、0.86±0.09 vs 1.02±0.08、0.79±0.07 vs 1.04±0.11。P<0.05)。结论低频脉冲电刺激对脑卒中后吞咽障碍患者临床症状改善明显,且可能通过Notch/NF-κB信号通路改善患者症状。

Objective To study the effect of low-frequency pulsed electrical stimulation on swallowing function and expression of neurogenic gene homologous protein(Notch)/nuclear transcription factor-κB(NF-κB)signaling pathway in patients with dysphagia after stroke.Methods From June 2021 to January 2023,a total of 120 patients with dysphagia after stroke were enrolled,which included 58 males and 62 females,aged 45-68 years old with mean age of 56.82 years old;disease course was 2-8 weeks with mean courses of 4.61 weeks.All of them were randomly divided into study group(n=60,conventional training+pulse electrical stimulation)and control group(n=60,conventional training)and received routine treatment such as nourishing brain nerve cells,reducing intracranial pressure,controlling brain edema,improving brain tissue circulation,and swallowing rehabilitation training.The study group was further performed with low-frequency pulse electrical stimulation on the basis.Before and after treatment,the swallowing function of 2 groups was detected according to Kubota drinking water test.The clinical efficacy of the patients was evaluated by referring Practical Techniques for Rehabilitation of Eating and Swallowing Disorders.The National Institute of Health stroke scale(NIHSS)score was evaluated before and after treatment.The expressions of Notch,Hes1,p-NF-κBp65/NF-κBp65 and Bax in blood were detected before and after treatment.Results After treatment,the scores of Kubota test were decreased in 2 groups,and it was significantly lower in study group than that of control group[(2.23±0.64)scores vs(3.02±0.81)scores.P<0.01].After treatment,the total effective rate of study group was significantly higher than that of control group(93.33%vs 75.00%.P<0.05).The NIHSS score of 2 groups decreased after treatment,and it was lower in study group than in control group[(10.32±1.85)scores vs(7.18±2.31)scores.P<0.05].After treatment,the expression levels of Notch,Hes1,p-NF-κBp65/NF-κBp65 and Bax protein were decreased in 2 groups(0.86±0.09 vs 1.42±0.12,0.74±0.11 vs 1.39±0.09,0.86±0.09 vs 1.52±0.14,0.79±0.07 vs 1.52±0.10.P<0.05),and the expression of Notch,Hes1,p-NF-κBp65/NF-κBp65 and Bax protein were significantly lower in study group than in control group(0.86±0.09 vs 1.12±0.10,0.74±0.11 vs 1.04±0.12,0.86±0.09 vs 1.02±0.08,0.79±0.07 vs 1.04±0.11.P<0.05).Conclusion It is demonstrated that lowfrequency pulsed electrical stimulation could significantly improve clinical symptoms of patients with dysphagia after stroke,and could improve symptoms of patients via Notch/NF-κB signaling pathway.