血清GABA、BDNF、5-HT、DA及NE在胃食管反流病中的表达及临床意义

Expression of serum GABA,BDNF,5-HT,DA,and NE in gastroesophageal reflux disease and its clinical significance

目的探讨血清γ-氨基丁酸(GABA)、脑源性营养因子(BDNF)、5-羟色胺(5-HT)、去甲肾上腺素(NE)及多巴胺(DA)在胃食管反流病(GERD)中的表达及临床意义。方法选取100例GERD患者作为GERD组、40例同期健康体检者为对照组,GERD组患者给予药物治疗8周,根据治疗效果分为效果良好组和效果不良组;对照组于体检时、GERD组于治疗前、治疗后(8周时)取外周静脉血,检测血清GABA、BDNF、5-HT、DA、NE、胃动素(MTL)、胃泌素(GAS)、胆囊收缩素(CCK)水平;采用匹兹堡睡眠质量指数(PSQI)、汉密尔顿抑郁量表(HAMD)、焦虑自评量表(SAS)、日常生活能力量表(ADL)评分评估GERD组治疗前后、对照组体检时的睡眠质量、抑郁程度、焦虑状态、日常生活能力;比较GERD患者治疗前后、效果良好及效果不良组食管括约压力、立位返流时间比、卧位反流时间比、总反流时间;采用Pearson分析GERD患者治疗前GABA、BDNF、5-HT、NE及DA水平与患者食管括约肌压力、立位返流时间比、卧位返流时间比、总返流时间比、MTL、GAS、CCK的相关性。结果GERD组治疗后血清GABA、BDNF、5-HT、NE、DA、MTL、GAS水平高于治疗前、但低于对照组,血清CCK水平及各量表评分均低于治疗前、但高于对照组(P<0.05);GERD组患者治疗后食管括约压力高于治疗前,立位返流时间比、卧位反流时间比、总反流时间均低于治疗前(P<0.05);30例疗效不良组GERD患者血清GABA、BDNF、5-HT、NE、DA、MTL、GAS水平及食管括约肌压力均低于70例疗效良好组,血清CCK水平、各量表评分、立位返流时间比、卧位反流时间比、总反流时间比均高于疗效良好组(P<0.05);GERD患者治疗前血清BDNF、5-HT、DA水平与MTL、GAS、食管括约肌压力呈正相关,与立位返流时间比、卧位反流时间比、总反流时间比、CCK呈负相关,GABA、NE与MTL、GAS、食管括约肌压力呈正相关,NE与立位返流时间比、CCK呈负相关性,GABA与立位返流时间比、总反流时间比、CCK呈负相关,差异有统计学意义(P<0.05)。结论GABA、BDNF、5-HT、NE及DA水平与胃内激素MTL、GAS、CCK的合成分泌及胃动力相关指标关系密切,这些神经递质可能参与GERD的发生和发展过程。

Objective To investigate the expression and clinical significance of serumγ-aminobutyric acid(GABA),brain-derived neurotrophic factor(BDNF),5-hydroxytryptamine(5-HT),norepinephrine(NE)and dopamine(DA)in gastroesophageal reflux disease(GERD).Methods One hundred patients with GERD were selected as the study group,and 40 healthy subjects as the control group.The levels of serum GABA,BDNF,5-HT,DA,NE,motilin(MTL),gastrin(GAS)and cholecystokinin(CCK)in patients with GERD were compared with those before treatment,8 weeks after treatment in the study group and during physical examination in the control group,8 weeks after treatment in the effective group and the ineffective group.Pittsburgh Sleep Quality Index(PSQI),Hamilton Depression Scale(HAMD),Self-rating Anxiety Scale(SAS),and Activity of Daily Living Scale(ADL)were used to evaluate the sleep quality,depression,anxiety,and daily living ability of the patients in the study group before and after treatment and the control group during physical examination.Compare the esophageal sphincter pressure,standing reflux time ratio,supine reflux time ratio,and total reflux time in GERD patients before and after treatment and betueen the groups with good and bad effects.Pearson correlation coefficient was used to analyze the correlation between the levels of GABA,BDNF,5-HT,NE,and DA in GERD patients before treatment and esophageal sphincter pressure,upright reflux time ratio,supine reflux time ratio,total reflux time ratio,MTL,GAS,and CCK.Results After treatment,the levels of serum GABA,BDNF,5-HT,NE,DA,MTL and GAS in the study group were higher than those before treatment but lower than those in the control group,and the levels of serum CCK and scores of each scale were lower than those before treatment but higher than those in the control group(P<0.05).In the study group,the esophageal sphincter pressure after treatment was higher than that before treatment,and the time ratio of vertical reflux,time ratio of supine reflux and total reflux time were lower than those before treatment(P<0.05).The levels of serum GABA,BDNF,5-HT,NE,DA,MTL,GAS,and esophageal sphincter pressure in 30 patients with GERD in the ineffective group were lower than those in 70 patients with GERD in the the effective group(P<0.05).The levels of serum CCK,scores of each scale,time ratio of reflux in standing position,time ratio of reflux in lying position and time ratio of total reflux in the ineffective group were higher than those in the effective group(P<0.05).The levels of serum BDNF,5-HT,and DA in GERD patients before treatment were positively correlated with MTL,GAS and esophageal sphincter pressure,and negatively correlated with upright reflux time ratio,supine reflux time ratio,total reflux time ratio,and CCK.GABA and NE were positively correlated with MTL,GAS and esophageal sphincter pressure.NE was negatively correlated with upright reflux time ratio and CCK.GABA was negatively correlated with upright reflux time ratio,total reflux time ratio and CCK.The difference was statistically significant(P<0.05).Conclusion The levels of GABA,BDNF,5-HT,NE,and DA are closely related to the synthesis and secretion of MTL,GAS,CCK,and gastric motility.The above neurotransmitters may be involved in the occurrence and development of GERD.