胃舒散对功能性消化不良的疗效与幽门螺杆菌的关系
吴灵飞, 郑宗茂, 李国平, 王炳周, 詹海勇, 曾哲, 周泽清，汕头大学医学院第二附属医院消化科 广东省汕头市 515041
吴灵飞，男，1964-9-26生，湖北省武汉市人，汉族.1992年湖北医科大学硕士研究生毕业，副主任医师.主要从事消化系统疾病的研究.
广东省中医药管理局资助项目，No.99591
项目负责人 吴灵飞，515041，广东省汕头市东厦北路广厦新城，汕头大学医学院第二附属医院消化科. lingfeiwu@21cn.com
电话: 0754-8355461 传真：0754-8346543
收稿日期 2001-12-20 接受日期 2002-01-04
Effect of weishusan on patients with functional dyspepsia and H. pylori infection
Ling-Fei Wu,Zong-Mao Zheng,Guo-Ping Li,Bing-Zhou Wang,Hai-Yong Zhan,Zhe Zeng，Ze-Qing Zhou
Ling-Fei Wu, Zong-Mao Zheng, Guo-Ping Li, Bing-Zhou Wang, Hai-Yong Zhan, Zhe Zeng，Ze-Qing Zhou,Department of Gsatroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong Province, China
Supported by Guangdong Chinese Traditional Medicine Management Agency, No.99591
Correspondence to: Dr. Ling-Fei Wu, Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College，Shantou 515041, Guangdong Province, China. lingfeiwu@21cn.com
Received 2001-12-20 Accepted 2001-01-04
Abstract
AIM:To evaluate the efficacy of weishusan on functional dyspepsia and to investigate the potential effect of eradication of H. pylori on gastritis and symptomatology of H. pylori -positive dyspepsia.
METHODS:Total 87 patients with functional dyspepsia were randomized to receive weishusan (3.0tid, n=56) or mosapride (5mg tid, n=31) for 4 weeks. The symptom score and severity of gastritis were assessed by clinical practitioners and endoscopy separately. Serum motilin (Mot), gastrin (Gas) and H. pylori were detected.
RESULTS:Symptom improvement was significant in weishusan group and mosapride group (85.7% vs 80.6%, NS). The motilin level was significantly higher after treatment in both groups (457±119ng·L-1 vs 410±106ng·L-1,P<0.01). The total effective rate of gastritis improvement in weishusan group (57.7%) was significantly higher than that in mosapride group (20.7%,P<0.01). Regarding H. pylori status, eradication of H. pylori was achieved in 41.9% (18/31) in weishusan group and no one in mosapride group (0/14,0%,P<0.01). No differences in the symptom score improvement were observed between patients with eradication, persistent infection and without infection. The gastritis improvement in patients with eradication (83.8%) was significantly higher than those without infection (47.2%,P<0.05), and those persistent infection (14.8%,P<0.01). The gastrin level in H. pylori positive patients was significantly higher than that in H. pylori negative patients (47±17ng·L-1 vs 36±13ng·L-1P<0.05). After eradication the gastrin level decreased but no significant differences were observed (P>0.05).
CONCLUSION:Weishusan is a good prokinetic drug and has effect on functional dyspepsia. It also has effects on protection of gastric mucosa and on eradication of H. pylori, which seems not to contribute to the timely symptom improvement of dyspepsia.
Wu LF, Zheng ZM, Li GP, Wang BZ, Zhan HY, Zeng Z, Zhou ZQ. Effect of weishusan on patients with functional dyspepsia and H. pylori infection.Shijie Huaren Xiaohua Zazhi 2002;10(3):275-278
摘要
目的:观察胃舒散对功能性消化不良的疗效并探讨其机制,同时探讨其与幽门螺杆菌的关系.
方法:选择FD患者87例，按性别、年龄分层后采用单育法随机分为二组：胃舒散组56例，服胃舒散3.0, 每天3次.莫沙必利组31例，服莫沙必利5mg，每天3次.疗程为6wk.采用症状积分及内镜下胃炎积分法，观察各组临床疗效及内镜下胃炎变化.同时检测治疗前后血浆胃动素(Mot), 促胃液素(Gas)和幽门螺杆菌(Hp).
结果:胃舒散和莫沙必利临床总有效率分别为85.7%和80.6%.疗效差异无显著性意义(P>0.05).二组治疗后Mot水平均较治疗前显著升高(457±119ng.L-1 vs 410±106ng.L-1, 469±130ng.L-1 vs 378±119ng.L-1,P<0.01)，Gas水平变化不明显(P>0.05).胃舒散对Hp的根除率(18/31，41.9%)显著高于莫沙必利(0/14，P<0.01).根据Hp情况分组，Hp根除组，Hp未根除组及Hp阴性组临床症状总有效率分别为88.9%,81.5%和83.3%,各组相比差异无显著性意义(P>0.05).内镜观察Hp根除组总有效率为83.3%,显著高于Hp未根除组(14.8%，P<0.01)及Hp阴性组(47.2%,P<0.05).Hp阴性组内镜下总有效率(47.2%)亦显著高于Hp未根除组(14.8%，P<0.05).Hp阳性患者Gas水平显著高于Hp阴性患者(47±17ng.L-1 vs 36±13ng.L-1,P<0.05).Hp根除后Gas有所下降，但经统计学处理，差异无显著性意义.
结论:胃舒散是治疗FD的有效药物，副作用少，其机制与提高Mot水平有关.胃舒散还有胃黏膜保护及杀灭Hp的作用.Hp的根除明显使内镜下胃炎程度减轻，但近期并不增加其缓解临床症状的效果.
吴灵飞, 郑宗茂, 李国平, 王炳周, 詹海勇, 曾哲,周泽清. 胃舒散对功能性消化不良的疗效与幽门螺杆菌的关系.
世界华人消化杂志 2002;10(3):275-278
0 引言
胃舒散是我院自行研制的复方中西药散剂，多年临床应用对功能性消化不良(FD)、慢性胃炎等疗效较好，但其机制不甚清楚.近年研究表明，胃动力障碍在FD中起重要作用[1，2]，但幽门螺杆菌(H.pylori, Hp)是否与FD有关尚有争论[3-6].我们以促动力药物莫沙必利为对照组，观察胃舒散对FD治疗前后胃动素(Mot)、促胃液素(Gas)及Hp的变化，以明确胃舒散的治疗效果及其机制，同时探讨其与Hp的关系.
1 材料和方法
1.1 材料 FD诊断采用罗马Ⅱ标准[7].2000-01/2001-08我院消化内科FD患者87例.先按性别、年龄分层，然后各层再用单盲法随机分为2组：胃舒散组56例，男26例，女30例，年龄(43±12)岁，病程(2.8±0.4)a.其中Hp阳性31例，占55.4%；莫沙必利组31例中，男14例、女17例，年龄(40±11)岁，病程(4.0±0.4)a. 其中Hp阳性14例，占43.7%.二组在年龄、性别、Hp感染率及病程方面差异无显著性意义(P>0.05).
1.2 方法 胃舒散组：胃舒散3.0g, 每天3次; 莫沙必利组：莫沙必利5mg，每天3次.均饭前服，疗程6wk.用药前1mo停止使用抗生素.用药期间禁止使用胃黏膜保护剂及其他促胃动力药物.主要症状(上腹饱胀、上腹痛、嗳气、早饱、厌食、恶心)按其有无及轻重程度进行评分(0～3分)[4].各项症状积分之和为总积分.内镜评分参照巴图法[8]根据胃黏膜有无炎症及其轻重程度进行分级(0-3级)并予相应评分(0～3分).治疗前先评定积分，治疗结束后再评积分比较.Hp检测采用14C-尿素酶呼气试验，血清学检测抗Hp抗体及组织切片Warthin-Starry染色法.三种方法中二种阳性即诊断Hp感染.治疗结束1mo后，使用14C-尿素酶呼气试验复查[9].所有病例均于治疗前后清晨空腹静脉采血，按照说明书以放射免疫法测定Mot及Gas含量.Mot试剂盒购自301医院科技开发中心放免所，Gas试剂盒购自北方生物技术研究所.
统计学处理 所有数据均采用x±s表示，用SPSS软件进行统计学处理.计量资料用t检验，计数资料用χ2检验或Ridit分析.
2 结果
2.1 疗效观察 根据临床症状及内镜下炎症改善程度分为显效、有效和无效.按公式计算积分变化以判断疗效，即：(治疗前积分-治疗后积分)/治疗前积分×100%.显效：积分减少2/3以上.有效：积分减少1/3不足2/3.无效：积分减少不足1/3.临床症状胃舒散组总有效率为85.7%，莫沙必利组总有效率为80.6%，经Ridit分析，两组疗效无显著性差异(P>0.05).内镜检查胃舒散组正常4例，莫沙必利组正常2例，故未复查内镜.内镜复查胃舒散组52例中，总有效率为57.7%；莫沙必利组29例，总有效率为20.7%，两组经统计学处理,差异有显著性意义(P<0.005).胃舒散组Hp阳性31例，治疗后转阴18例，根除率为41.9%.莫沙必利组Hp阳性14例，无一例转阴，Hp根除率为0,二组差异有高度显著性意义(P<0.01).根据Hp情况及是否根除将其分为3组，观察Hp与疗效的关系，可见各组临床疗效无显著性差异(P>0.05) .内镜观察Hp根除组总有效率为83.3%,显著高于Hp未根除组(14.8%，P<0.01)及Hp阴性组(47.2%,P<0.05).Hp阴性组内镜下总有效率(47.2%)亦显著高于Hp未根除组(14.8%，P<0.05).
2.2 Mot、Gas治疗前后的变化 治疗前二组Mot、Gas含量均无显著性差异，治疗后二组Mot水平均较治疗前显著提高，有统计学意义(P<0.01).Gas含量在治疗前后变化不明显(P>0.05, 表1).Hp阳性组Gas含量显著高于Hp阴性组(P<0.05).Hp根除后Gas水平有所下降，但与治疗前相比，无统计学意义(P>0.05).Hp阴性组及Hp未根除组Gas水平治疗前后亦无显著变化(P>0.05).各组治疗后Mot均显著高于治疗前水平(P<0.05，表2).莫沙必利组1例出现头晕,2例有轻度腹泻, 副反应发生率为9.7%.胃舒散组无1例出现副反应.
表1 治疗后血浆Mot、Gas水平变化 (x±s,ng·L-1)
aP<0.01 vs 治疗前
表2 治疗前后Hp与血浆Mot、Gas水平变化的比较(x±s,ng·L-1)
aP<0.05 vs Hp阴性组；bP<0.05 vs 治疗前
3 讨论
中医药在胃肠非器质性疾病的治疗中有悠久的历史[10-14].有些中药成分还具有杀灭Hp的作用.FD在中医诊断上属“胃脘痛”、“痞满”等病范畴，其病机主要为气机紊乱，脾胃升清降浊功能失司.按照中医观点，脾胃为五脏六腑之中枢，胃主受纳、腐熟、脾主运化、传输.脾喜燥而恶湿，脾气宜升，得阳则运，胃喜润而恶澡，胃气宜降宜和，得阴始安.脾与胃升降机同，燥湿相济，共同完成水谷的消化吸收.若脾虚失运，则腹胀气闷，便塘乏力.若胃阴不足，则易饱纳呆，通化无力.本病证属本虚标实.脾气虚弱为其本，病因与饮食失节，情志所伤，长期脾胃留邪未去及肝肾等脏腑功能失调有关.标实主要为气郁、湿阻、食滞、血淤等.因而治疗主要在于理气、健脾，以调节其功能障碍[15-17].根据长期的临床经验，我院自行研制的胃舒散，其功效主要为健脾和胃，调理气机，对FD患者其总有效率为85.7%且无副作用，效果令人满意.中药对胃肠运动调节的研究近年发展较快[18-20].由于胃肠激素在此领域有重要地位，有关研究报道不少[21-23].Mot的功能主要与消化间期移行性运动复合波(MMC)Ⅲ相有关.MMCⅢ相在胃肠协调性运动，清除内容物，防止细菌过度生长及发生饥饿信号等方面起重要作用.消化间期Mot呈周期性变化，从而使胃肠出现节律性运动.研究表明，FD患者血浆Mot水平较低下，表现为空腹血浆Mot无峰值出现，或峰值低于正常值.进食后亦无明显峰值出现，常伴有胃排空障碍[24，25].在模拟脾虚症的动物实验及临床实践中，常观察到胃肠运动减弱，胃顺应性降低及胃电节律异常，这些现象与血浆及组织中Mot等含量改变有关[26-28].给予四君子汤，枳实消痞丸[29]则能显著提高Mot含量并改善胃动力. 谭余庆 et al报道中药桂枝汤还显示出双向调节胃肠动力的作用[30].单味中药如木香[31]，枳实[32], 石菖蒲[33]等亦有较好促进胃肠运动的效果.我院研制的胃舒散主要成分由木香，陈皮，鸡骨香，石菖蒲等组成，均有不同的理气功效.FD患者服用后Mot水平显著高于治疗前，与有关的研究结果一致[3,31-35]，类似于莫沙必利的促动力效果，说明其理气亦是通过Mot介导而起作用.
Hp在FD中的作用仍有争论[3-6,36-39].Hp引起的胃炎可能使内脏神经敏感性、感觉阈异常而出现消化不良的症状.Tucci et al[40]认为Hp引起的胃炎参与了FD的病理生理过程.但亦有人观察到一些Hp阳性患者并不出现FD症状，FD患者Hp阳性的概率并不比其他人更高.抗Hp治疗引起耐药菌株的产生以及可能引起胃食管反流病的担忧[41]，尤其是一些研究显示Hp根除治疗并未对FD患者产生预期的效果，使人们对Hp阳性FD患者进行Hp的根除治疗持怀疑态度. 然而，愈来愈多的证据表明Hp与FD有关[36-38,42].根除Hp有助于消除活动性胃炎已成共识[43].在我们的研究中亦观察到尽管临床症状胃舒散组与莫沙必利组疗效无显著性差异，但二组6wk疗程结束后内镜下疗效有明显差别，胃舒散显示出较好的杀灭Hp及胃黏膜保护作用.近年中医药治疗Hp感染已取得一定成绩.黄连，大黄，黄芩等已证实均有不同程度的抗菌作用[44].胃舒散除中药成分外还含有次碳酸铋，我们认为均与其杀菌作用有关.根据Hp情况分组，Hp根除组内镜下胃炎总有效率为83.3%,显著高于Hp未根除组(14.8%),显示了杀菌对Hp阳性患者的重要性，与Frochlich结果一致[36].在临床经验中，Hp阳性的FD患者多伴有活动性胃炎，部分可发展为消化性溃疡，另一部分还可进展为萎缩性胃炎[40].FD作为一种异质性疾病，患者一般不需内镜复查，因而症状的疗效可能会掩盖组织学的差异.从内镜疗效观察到Hp根除与Hp持续感染二组的显著差别，我们认为对这些患者确应给予Hp根除治疗.FD症状易反复再现的特点，若给予更长时间的观察，相信根除Hp会取得更好的效果.在本项研究中，除了6例内镜诊断正常外，其余均诊断胃炎.实际上不少内镜下诊断胃炎的患者并无明显组织学炎症的改变，这亦是本组内镜下胃炎阳性率较高而好转较少的原因.内镜下胃炎的诊断标准尚需进一步完善.Bojarrski et al[45]研究发现，若排除其他原因，单纯由Hp引起的消化不良症状，根除Hp后85%的患者症状得到缓解.Blum et al[46]在一项双盲多中心的研究中发现使用质子泵抑制剂(20mg/d)对Hp阳性的FD患者缓解症状及提高生活质量有肯定的效果，认为与抑制Hp导致的过强胃酸有关,根除Hp有助于缓解消化不良症状，并能防止消化性溃疡及胃癌的发生.Hp及其代谢产物，Hp相关性胃炎及FD三者之间的关系有待进一步研究[47].
在本项研究中，二组治疗后Gas均无明显变化，说明胃舒散、莫沙必利的治疗效果与Gas无关.治疗后无论Hp是否根除或无Hp感染，Mot水平均显著性高于治疗前，亦说明二种药物的促动力作用与Hp状态无关.若根据Hp进行分组，Hp阳性组Gas水平显著高于Hp阴性组，显示Hp感染导致了高Gas血症，与文献报道相一致.Chiloiro et al[3]观察到根除Hp后随胃炎好转Gas水平下降.在本研究中Hp杀灭后Gas水平有所降低但无统计学意义.我们推测Hp杀灭后胃黏膜炎性组织的修复，局部内分泌细胞调节的适应可能需要一定的时间.Gas含量的变化有待更长时间的观察.
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吴灵飞，男，1964-9-26生，湖北省武汉市人，汉族.1992年湖北医科大学硕士研究生毕业，副主任医师.主要从事消化系统疾病的研究.
广东省中医药管理局资助项目，No.99591
项目负责人 吴灵飞，515041，广东省汕头市东厦北路广厦新城，汕头大学医学院第二附属医院消化科. lingfeiwu@21cn.com
电话: 0754-8355461 传真：0754-8346543
收稿日期 2001-12-20 接受日期 2002-01-04
Effect of weishusan on patients with functional dyspepsia and H. pylori infection
Ling-Fei Wu,Zong-Mao Zheng,Guo-Ping Li,Bing-Zhou Wang,Hai-Yong Zhan,Zhe Zeng，Ze-Qing Zhou
Ling-Fei Wu, Zong-Mao Zheng, Guo-Ping Li, Bing-Zhou Wang, Hai-Yong Zhan, Zhe Zeng，Ze-Qing Zhou,Department of Gsatroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong Province, China
Supported by Guangdong Chinese Traditional Medicine Management Agency, No.99591
Correspondence to: Dr. Ling-Fei Wu, Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College，Shantou 515041, Guangdong Province, China. lingfeiwu@21cn.com
Received 2001-12-20 Accepted 2001-01-04
Abstract
AIM:To evaluate the efficacy of weishusan on functional dyspepsia and to investigate the potential effect of eradication of H. pylori on gastritis and symptomatology of H. pylori -positive dyspepsia.
METHODS:Total 87 patients with functional dyspepsia were randomized to receive weishusan (3.0tid, n=56) or mosapride (5mg tid, n=31) for 4 weeks. The symptom score and severity of gastritis were assessed by clinical practitioners and endoscopy separately. Serum motilin (Mot), gastrin (Gas) and H. pylori were detected.
RESULTS:Symptom improvement was significant in weishusan group and mosapride group (85.7% vs 80.6%, NS). The motilin level was significantly higher after treatment in both groups (457±119ng·L-1 vs 410±106ng·L-1,P<0.01). The total effective rate of gastritis improvement in weishusan group (57.7%) was significantly higher than that in mosapride group (20.7%,P<0.01). Regarding H. pylori status, eradication of H. pylori was achieved in 41.9% (18/31) in weishusan group and no one in mosapride group (0/14,0%,P<0.01). No differences in the symptom score improvement were observed between patients with eradication, persistent infection and without infection. The gastritis improvement in patients with eradication (83.8%) was significantly higher than those without infection (47.2%,P<0.05), and those persistent infection (14.8%,P<0.01). The gastrin level in H. pylori positive patients was significantly higher than that in H. pylori negative patients (47±17ng·L-1 vs 36±13ng·L-1P<0.05). After eradication the gastrin level decreased but no significant differences were observed (P>0.05).
CONCLUSION:Weishusan is a good prokinetic drug and has effect on functional dyspepsia. It also has effects on protection of gastric mucosa and on eradication of H. pylori, which seems not to contribute to the timely symptom improvement of dyspepsia.
Wu LF, Zheng ZM, Li GP, Wang BZ, Zhan HY, Zeng Z, Zhou ZQ. Effect of weishusan on patients with functional dyspepsia and H. pylori infection.Shijie Huaren Xiaohua Zazhi 2002;10(3):275-278
摘要
目的:观察胃舒散对功能性消化不良的疗效并探讨其机制,同时探讨其与幽门螺杆菌的关系.
方法:选择FD患者87例，按性别、年龄分层后采用单育法随机分为二组：胃舒散组56例，服胃舒散3.0, 每天3次.莫沙必利组31例，服莫沙必利5mg，每天3次.疗程为6wk.采用症状积分及内镜下胃炎积分法，观察各组临床疗效及内镜下胃炎变化.同时检测治疗前后血浆胃动素(Mot), 促胃液素(Gas)和幽门螺杆菌(Hp).
结果:胃舒散和莫沙必利临床总有效率分别为85.7%和80.6%.疗效差异无显著性意义(P>0.05).二组治疗后Mot水平均较治疗前显著升高(457±119ng.L-1 vs 410±106ng.L-1, 469±130ng.L-1 vs 378±119ng.L-1,P<0.01)，Gas水平变化不明显(P>0.05).胃舒散对Hp的根除率(18/31，41.9%)显著高于莫沙必利(0/14，P<0.01).根据Hp情况分组，Hp根除组，Hp未根除组及Hp阴性组临床症状总有效率分别为88.9%,81.5%和83.3%,各组相比差异无显著性意义(P>0.05).内镜观察Hp根除组总有效率为83.3%,显著高于Hp未根除组(14.8%，P<0.01)及Hp阴性组(47.2%,P<0.05).Hp阴性组内镜下总有效率(47.2%)亦显著高于Hp未根除组(14.8%，P<0.05).Hp阳性患者Gas水平显著高于Hp阴性患者(47±17ng.L-1 vs 36±13ng.L-1,P<0.05).Hp根除后Gas有所下降，但经统计学处理，差异无显著性意义.
结论:胃舒散是治疗FD的有效药物，副作用少，其机制与提高Mot水平有关.胃舒散还有胃黏膜保护及杀灭Hp的作用.Hp的根除明显使内镜下胃炎程度减轻，但近期并不增加其缓解临床症状的效果.
吴灵飞, 郑宗茂, 李国平, 王炳周, 詹海勇, 曾哲,周泽清. 胃舒散对功能性消化不良的疗效与幽门螺杆菌的关系.
世界华人消化杂志 2002;10(3):275-278
0 引言
胃舒散是我院自行研制的复方中西药散剂，多年临床应用对功能性消化不良(FD)、慢性胃炎等疗效较好，但其机制不甚清楚.近年研究表明，胃动力障碍在FD中起重要作用[1，2]，但幽门螺杆菌(H.pylori, Hp)是否与FD有关尚有争论[3-6].我们以促动力药物莫沙必利为对照组，观察胃舒散对FD治疗前后胃动素(Mot)、促胃液素(Gas)及Hp的变化，以明确胃舒散的治疗效果及其机制，同时探讨其与Hp的关系.
1 材料和方法
1.1 材料 FD诊断采用罗马Ⅱ标准[7].2000-01/2001-08我院消化内科FD患者87例.先按性别、年龄分层，然后各层再用单盲法随机分为2组：胃舒散组56例，男26例，女30例，年龄(43±12)岁，病程(2.8±0.4)a.其中Hp阳性31例，占55.4%；莫沙必利组31例中，男14例、女17例，年龄(40±11)岁，病程(4.0±0.4)a. 其中Hp阳性14例，占43.7%.二组在年龄、性别、Hp感染率及病程方面差异无显著性意义(P>0.05).
1.2 方法 胃舒散组：胃舒散3.0g, 每天3次; 莫沙必利组：莫沙必利5mg，每天3次.均饭前服，疗程6wk.用药前1mo停止使用抗生素.用药期间禁止使用胃黏膜保护剂及其他促胃动力药物.主要症状(上腹饱胀、上腹痛、嗳气、早饱、厌食、恶心)按其有无及轻重程度进行评分(0～3分)[4].各项症状积分之和为总积分.内镜评分参照巴图法[8]根据胃黏膜有无炎症及其轻重程度进行分级(0-3级)并予相应评分(0～3分).治疗前先评定积分，治疗结束后再评积分比较.Hp检测采用14C-尿素酶呼气试验，血清学检测抗Hp抗体及组织切片Warthin-Starry染色法.三种方法中二种阳性即诊断Hp感染.治疗结束1mo后，使用14C-尿素酶呼气试验复查[9].所有病例均于治疗前后清晨空腹静脉采血，按照说明书以放射免疫法测定Mot及Gas含量.Mot试剂盒购自301医院科技开发中心放免所，Gas试剂盒购自北方生物技术研究所.
统计学处理 所有数据均采用x±s表示，用SPSS软件进行统计学处理.计量资料用t检验，计数资料用χ2检验或Ridit分析.
2 结果
2.1 疗效观察 根据临床症状及内镜下炎症改善程度分为显效、有效和无效.按公式计算积分变化以判断疗效，即：(治疗前积分-治疗后积分)/治疗前积分×100%.显效：积分减少2/3以上.有效：积分减少1/3不足2/3.无效：积分减少不足1/3.临床症状胃舒散组总有效率为85.7%，莫沙必利组总有效率为80.6%，经Ridit分析，两组疗效无显著性差异(P>0.05).内镜检查胃舒散组正常4例，莫沙必利组正常2例，故未复查内镜.内镜复查胃舒散组52例中，总有效率为57.7%；莫沙必利组29例，总有效率为20.7%，两组经统计学处理,差异有显著性意义(P<0.005).胃舒散组Hp阳性31例，治疗后转阴18例，根除率为41.9%.莫沙必利组Hp阳性14例，无一例转阴，Hp根除率为0,二组差异有高度显著性意义(P<0.01).根据Hp情况及是否根除将其分为3组，观察Hp与疗效的关系，可见各组临床疗效无显著性差异(P>0.05) .内镜观察Hp根除组总有效率为83.3%,显著高于Hp未根除组(14.8%，P<0.01)及Hp阴性组(47.2%,P<0.05).Hp阴性组内镜下总有效率(47.2%)亦显著高于Hp未根除组(14.8%，P<0.05).
2.2 Mot、Gas治疗前后的变化 治疗前二组Mot、Gas含量均无显著性差异，治疗后二组Mot水平均较治疗前显著提高，有统计学意义(P<0.01).Gas含量在治疗前后变化不明显(P>0.05, 表1).Hp阳性组Gas含量显著高于Hp阴性组(P<0.05).Hp根除后Gas水平有所下降，但与治疗前相比，无统计学意义(P>0.05).Hp阴性组及Hp未根除组Gas水平治疗前后亦无显著变化(P>0.05).各组治疗后Mot均显著高于治疗前水平(P<0.05，表2).莫沙必利组1例出现头晕,2例有轻度腹泻, 副反应发生率为9.7%.胃舒散组无1例出现副反应.
表1 治疗后血浆Mot、Gas水平变化 (x±s,ng·L-1)
| 分组 | n | 治疗前 | 治疗后 | ||
| Mot | Gas | Mot | Gas | ||
| 胃舒散组 | 56 | 411±106 | 43±14 | 457±119a | 38±17 |
| 莫沙必利组 | 31 | 378±119 | 46±18 | 469±130a | 40±16 |
aP<0.01 vs 治疗前
表2 治疗前后Hp与血浆Mot、Gas水平变化的比较(x±s,ng·L-1)
| Hp | n | 治疗前 | 治疗后 | ||
| Mot | Gas | Mot | Gas | ||
| 根除组 | 18 | 403±112 | 46±15a | 458±130b | 39±13 |
| 未根除组 | 27 | 397±106 | 47±19a | 461±95b | 42±16 |
| 阴性组 | 42 | 379±127 | 36±13 | 440±102b | 39±13 |
aP<0.05 vs Hp阴性组；bP<0.05 vs 治疗前
3 讨论
中医药在胃肠非器质性疾病的治疗中有悠久的历史[10-14].有些中药成分还具有杀灭Hp的作用.FD在中医诊断上属“胃脘痛”、“痞满”等病范畴，其病机主要为气机紊乱，脾胃升清降浊功能失司.按照中医观点，脾胃为五脏六腑之中枢，胃主受纳、腐熟、脾主运化、传输.脾喜燥而恶湿，脾气宜升，得阳则运，胃喜润而恶澡，胃气宜降宜和，得阴始安.脾与胃升降机同，燥湿相济，共同完成水谷的消化吸收.若脾虚失运，则腹胀气闷，便塘乏力.若胃阴不足，则易饱纳呆，通化无力.本病证属本虚标实.脾气虚弱为其本，病因与饮食失节，情志所伤，长期脾胃留邪未去及肝肾等脏腑功能失调有关.标实主要为气郁、湿阻、食滞、血淤等.因而治疗主要在于理气、健脾，以调节其功能障碍[15-17].根据长期的临床经验，我院自行研制的胃舒散，其功效主要为健脾和胃，调理气机，对FD患者其总有效率为85.7%且无副作用，效果令人满意.中药对胃肠运动调节的研究近年发展较快[18-20].由于胃肠激素在此领域有重要地位，有关研究报道不少[21-23].Mot的功能主要与消化间期移行性运动复合波(MMC)Ⅲ相有关.MMCⅢ相在胃肠协调性运动，清除内容物，防止细菌过度生长及发生饥饿信号等方面起重要作用.消化间期Mot呈周期性变化，从而使胃肠出现节律性运动.研究表明，FD患者血浆Mot水平较低下，表现为空腹血浆Mot无峰值出现，或峰值低于正常值.进食后亦无明显峰值出现，常伴有胃排空障碍[24，25].在模拟脾虚症的动物实验及临床实践中，常观察到胃肠运动减弱，胃顺应性降低及胃电节律异常，这些现象与血浆及组织中Mot等含量改变有关[26-28].给予四君子汤，枳实消痞丸[29]则能显著提高Mot含量并改善胃动力. 谭余庆 et al报道中药桂枝汤还显示出双向调节胃肠动力的作用[30].单味中药如木香[31]，枳实[32], 石菖蒲[33]等亦有较好促进胃肠运动的效果.我院研制的胃舒散主要成分由木香，陈皮，鸡骨香，石菖蒲等组成，均有不同的理气功效.FD患者服用后Mot水平显著高于治疗前，与有关的研究结果一致[3,31-35]，类似于莫沙必利的促动力效果，说明其理气亦是通过Mot介导而起作用.
Hp在FD中的作用仍有争论[3-6,36-39].Hp引起的胃炎可能使内脏神经敏感性、感觉阈异常而出现消化不良的症状.Tucci et al[40]认为Hp引起的胃炎参与了FD的病理生理过程.但亦有人观察到一些Hp阳性患者并不出现FD症状，FD患者Hp阳性的概率并不比其他人更高.抗Hp治疗引起耐药菌株的产生以及可能引起胃食管反流病的担忧[41]，尤其是一些研究显示Hp根除治疗并未对FD患者产生预期的效果，使人们对Hp阳性FD患者进行Hp的根除治疗持怀疑态度. 然而，愈来愈多的证据表明Hp与FD有关[36-38,42].根除Hp有助于消除活动性胃炎已成共识[43].在我们的研究中亦观察到尽管临床症状胃舒散组与莫沙必利组疗效无显著性差异，但二组6wk疗程结束后内镜下疗效有明显差别，胃舒散显示出较好的杀灭Hp及胃黏膜保护作用.近年中医药治疗Hp感染已取得一定成绩.黄连，大黄，黄芩等已证实均有不同程度的抗菌作用[44].胃舒散除中药成分外还含有次碳酸铋，我们认为均与其杀菌作用有关.根据Hp情况分组，Hp根除组内镜下胃炎总有效率为83.3%,显著高于Hp未根除组(14.8%),显示了杀菌对Hp阳性患者的重要性，与Frochlich结果一致[36].在临床经验中，Hp阳性的FD患者多伴有活动性胃炎，部分可发展为消化性溃疡，另一部分还可进展为萎缩性胃炎[40].FD作为一种异质性疾病，患者一般不需内镜复查，因而症状的疗效可能会掩盖组织学的差异.从内镜疗效观察到Hp根除与Hp持续感染二组的显著差别，我们认为对这些患者确应给予Hp根除治疗.FD症状易反复再现的特点，若给予更长时间的观察，相信根除Hp会取得更好的效果.在本项研究中，除了6例内镜诊断正常外，其余均诊断胃炎.实际上不少内镜下诊断胃炎的患者并无明显组织学炎症的改变，这亦是本组内镜下胃炎阳性率较高而好转较少的原因.内镜下胃炎的诊断标准尚需进一步完善.Bojarrski et al[45]研究发现，若排除其他原因，单纯由Hp引起的消化不良症状，根除Hp后85%的患者症状得到缓解.Blum et al[46]在一项双盲多中心的研究中发现使用质子泵抑制剂(20mg/d)对Hp阳性的FD患者缓解症状及提高生活质量有肯定的效果，认为与抑制Hp导致的过强胃酸有关,根除Hp有助于缓解消化不良症状，并能防止消化性溃疡及胃癌的发生.Hp及其代谢产物，Hp相关性胃炎及FD三者之间的关系有待进一步研究[47].
在本项研究中，二组治疗后Gas均无明显变化，说明胃舒散、莫沙必利的治疗效果与Gas无关.治疗后无论Hp是否根除或无Hp感染，Mot水平均显著性高于治疗前，亦说明二种药物的促动力作用与Hp状态无关.若根据Hp进行分组，Hp阳性组Gas水平显著高于Hp阴性组，显示Hp感染导致了高Gas血症，与文献报道相一致.Chiloiro et al[3]观察到根除Hp后随胃炎好转Gas水平下降.在本研究中Hp杀灭后Gas水平有所降低但无统计学意义.我们推测Hp杀灭后胃黏膜炎性组织的修复，局部内分泌细胞调节的适应可能需要一定的时间.Gas含量的变化有待更长时间的观察.
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