柴胡疏肝散合旋覆代赭汤加减治疗伴焦虑、抑郁的胃食管反流病的临床疗效

Clinical Efficacy of Modified Chaihu Shugansan Combined with Xuanfu Daizhetang on Depression of Patients of Patients with Gastroesophageal Reflux Disease

目的:观察柴胡疏肝散合旋覆代赭汤加减联合抑酸剂治疗伴焦虑、抑郁的胃食管反流病(GERD)气郁痰阻证的临床疗效及对神经肽因子和促炎因子的影响。方法:按照随机数字表法将200例患者分为观察组(100例)和对照组(100例)。对照组口服奥美拉唑肠溶片,20 mg/次,1次/d;氟哌噻吨美利曲辛片,1片/次,2次/d;达立通颗粒,1袋/次,3次/d。观察组口服奥美拉唑肠溶片同对照组,并内服柴胡疏肝散合旋覆代赭汤加减,1剂/d。两组疗程均为8周。进行治疗前后反酸、烧心、胸骨后疼痛等主要症状评分和上消化道内镜检查;进行治疗前后汉密尔顿焦虑量表-14(HAMA-14),气郁痰阻证评分、胃食管反流病问卷(GerdQ)和汉密尔顿抑郁量表-17(HAMD-17)评分;检测治疗前后外周血管活性肠肽(VIP),5-羟色胺(5-HT),肿瘤坏死因子-α(TNF-α),白细胞介素-1(IL-1)和IL-6水平;对所有GerdQ<8分患者进行16周的随访,记录复发情况;进行安全性评价。结果:治疗后观察组患者GerdQ评分、内镜评分和主要症状积分均低于对照组(P<0.01);观察组气郁痰阻证积分低于对照组(P<0.01),治疗后两组患者HAMA-14评分和HAMD-17评分均有下降(P<0.01),但治疗后组间差异无统计学意义;观察组主要症状综合疗效高于对照组(Z=2.076,P<0.05);观察组中医证候疗效高于对照组组(Z=2.151,P<0.01);观察组内镜疗效高于对照组(Z=2.103,P<0.05);观察组VIP,5-HT,TNF-α,IL-1和IL-6水平均低于对照组;在16周随访期间,观察组复发率为19.23%(15/78),明显低于对照组的35.38%(23/65)(χ^(2)=4.741,P<0.05);观察组的平均复发时间低于对照组(P<0.01)。结论:柴胡疏肝散合旋覆代赭汤加减联合奥美拉唑肠溶片治疗伴焦虑、抑郁的GERD(气郁痰阻证)患者近期可显著改善主要症状和中医证候,并可减轻抑郁、焦虑等不良情绪,促进食管黏膜的愈合,远期可降低复发率并推迟复发的时间,其作用机制可能与调节神经肽因子和抑制促炎因子的表达有关。

Objective: To observe the clinical efficacy modified Chaihu Shugansan combined with Xuanfu Daizhetang on anxiety and depression of patients with gastroesophageal reflux disease(GERD)and Qi stagnation and phlegm obstruction syndromes in clinic and the effect on neuropeptide factor and proinflammatory factor. Method: Patients 200 cases were divided into control group and observation group.Patients in control group got omeprazole enteric-coated tablets, 20 mg/time, 1 time/day, flupentixol and melitracen tablets,1 tablet/time,2 times/day,and Dalitong granules,1 bag/time,3 times/day. In addition to omeprazole enteric-coated tablets in control group,patients in observation group were also added with syndrome differentiation-based treatment of modified Chaihu Shugansan combined with Xuanfu Daizhetang,1 dose/day.The treatment lasted for 8 weeks. Before and after treatment,scores of acid regurgitation,heartburn,poststernal pain, syndrome of Qi stagnation and phlegm obstruction, gastroesophageal reflux disease questionnaire(GerdQ),Hamilton anxiety Scale-14(HAMA-14)and Hamilton depression scale-17(HAMD-17)were scored;And upper gastrointestinal endoscopy, levels of peripheral vasoactive intestinal peptide(VIP),5-hydroxytryptamine(5-HT),tumor necrosis factor-α(TNF-α),interleukin-1(IL-1),IL-6 were detected. All the patients(GerdQ<8)got follow-up for 16 weeks,and the recurrence and safety were recorded. Result:After treatment,scores of GerdQ,endoscope,main symptoms and syndrome of Qi stagnation and phlegm obstruction on observation group were lower than those in control group(P<0.01),and scores of HAMA-14 and HAMD-17 decreased in both groups(P<0.01), but with no statistically significant difference in both groups. The comprehensive efficacy of main symptoms in observation group was better than that in control group(Z=2.076,P<0.05). The curative effect of traditional Chinese medicine(TCM) syndrome in observation group was superior to that in control group(Z=2.151,P<0.01). The effect of endoscope was better than that in control group(Z=2.103,P<0.05). And levels of VIP,5-HT,TNF-α,IL-1 and IL-6 in observation group were lower than those in control group. During the 16-week follow-up,the recurrence rate in observation group was 19.23%(15/78),which was lower than 35.38%(23/65)in control group(χ^(2)=4.741,P<0.05). The average recurrence time of the observation group was lower than that of the control group(P<0.01). Conclusion: Modified Chaihu Shugansan combined with Xuanfu Daizhetang can significantly improve the main symptoms and TCM syndromes,relieve depression,anxiety and other adverse emotions,promote the healing of gastroesophageal mucosa,reduce the recurrence rate and delay the recurrence time among patients with GERD and Qi stagnation and phlegm obstruction syndromes. The mechanism of action may be related to the expression of neuropeptide factor and the inhibition of pro-inflammatory factor.