临床研究 Open Access
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
世界华人消化杂志. 2004-03-15; 12(3): 719-722
在线出版日期: 2004-03-15. doi: 10.11569/wcjd.v12.i3.719
脾气虚证患者血浆和组织中SS、Mot、CCK的变化
任平, 黄熙, 张航向, 黄裕新, 杨喜忠, 赵保民
任平, 黄熙, 张航向, 杨喜忠, 中国人民解放军第四军医大学附属西京医院 陕西省西安市 710032
黄裕新, 赵保民, 中国人民解放军第四军医大学附属唐都医院 陕西省西安市 710038
任平, 女, 1962-11-28生, 重庆市人, 汉族, 1984湖南中医学院本科毕业, 1991年第四军医大学硕士毕业, 副主任医师, 副教授, 主要从事中西医结合证本质中药临床药理学研究.
基金项目: 国家自然科学基金资助项目, No. 30271648; 国家中医药管理局资助课题, No. 02-03JP45.
通讯作者: 任平, 710032, 陕西省西安市长乐西路17号, 中国人民解放军第四军医大学附属西京医院老年病一科. tcmwsh@fmmu.edu.cn
电话: 029-3375956
收稿日期: 2003-08-07
修回日期: 2003-08-25
接受日期: 2003-10-07
在线出版日期: 2004-03-15

目的: 通过观察四君子汤对脾气虚证患者血浆和胃窦黏膜组织中胃动素(Mot)、生长抑素(SS)、胆囊收缩素(CCK)的影响, 探讨脾气虚证临床辨证的客观定量指标.

方法: 用放射免疫分析法(RIA)动态观察服药前后脾气虚证和胃热炽盛患者血浆和胃窦黏膜组织中Mot、SS和CCK的变化.

结果: (a)脾气虚证患者组织及血浆中Mot水平服药前显著低于胃热炽盛组及服药后, (胃窦组织: 109.4±18.9 ng/g vs 219.8±25.3 ng/g及183.0±23.9 ng/g; 血浆: 61.7±10.6 ng/L vs 171.4±30.8 ng/L及126.3±24.6 ng/L)(P<0.01); (b)脾气虚证患者组织和血浆中SS含量服药前显著高于胃热炽盛组及服药后, (胃窦黏膜: 224.3±67.9 ng/g vs 80.2±25.6 ng/g及114.2±34.5 ng/g; 血浆: 74.5±17.2 ng/L vs 30.3±11.8 ng/L及38.1±12.7 ng/L)(P<0.01); (c)脾气虚证患者组织和血浆中CCK含量服药前显著高于胃热炽盛组及服药后, (胃窦黏膜组织: 34.1±5.2 ng/g vs 21.6±4.7 ng/g及29.8±6.8 ng/g; 血浆: 5.8±0.4 ng/L vs 3.7±0.6 ng/L及2.9±0.8 ng/L)(P<0.01); (d)胃热炽盛组在服药后Mot、SS和CCK在血浆和组织中的含量变化不明显(P>0.05)(数字略).

结论: Mot、SS和CCK的浓度变化对脾气虚证的临床辨证施治可能有重要的参考价值.

关键词: N/A
引文著录: 任平, 黄熙, 张航向, 黄裕新, 杨喜忠, 赵保民. 脾气虚证患者血浆和组织中SS、Mot、CCK的变化. 世界华人消化杂志 2004; 12(3): 719-722
Changs of somatostatin, motilin and cholecystokinin in gastric antrum tissue and plasma in patients with spleen-asthenia
Ping Ren, Xi Huang, Hang-Xiang Zhang, Yu-Xin Huang, Xi-Zong Yang, Bao-Ming Zhao
Ping Ren, Xi Huang, Hang-Xiang Zhang, Xi-Zong Yang, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
Yu-Xin Huang, Bao-Ming Zhao, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China
Supported by: Natural Science Foundation of China and the Administrative Bureau Foundation of the Chinese Medicine and Pharmacology.
Correspondence to: Dr. Ping Ren, The First Department of Geriatrics,Xijing Hospital, Fourth Military Medical University, Xi'an 710032,Shaanxi Province, China. tcmwsh@fmmu.edu.cn
Received: August 7, 2003
Revised: August 25, 2003
Accepted: October 7, 2003
Published online: March 15, 2004

AIM: To explore the objective quantitative index of spleen-asthenia by investigating the effects of Sijunzhi decoction on the somatostatin, motilin and cholecystokinin in gastric antrum tissues and plasma in patients with spleen-asthenia.

METHODS: The levels of somatostatin (SS), motilin (Mot) and cholecystokinin (CCK) in gastric antrum tissues and plasma in patients with spleen-asthenia and stomach-heat were observed before and after treatment by RIA, respectively.

RESULTS: Compared with the stomach-heat and the spleen-asthenia treated by Sijunzhi decoction, patients with spleen-asthenia before the treatment had significantly higher level of motilin both in the tissues and plasma (109.4±18.9 ng/g vs 219.8±25.3 ng/g, and 183.0±23.9 ng/g; plasma: 61.7±10.6 ng/L vs 171.4±30.8 ng/L, and 126.3± 24.6 ng/L) (P < 0.01); The SS contents in the tissues and plasma were increased "antrum" (224.3±67.9 ng/g vs 80.2±25.6 ng/g, and 114.2± 34.5 ng/g; plasma: 74.5±17.2 ng/L vs 30.3±11.8 ng/L, and 38.1v12.7 ng/L) (P < 0.01): The CCK levels in gastric antrum and plasma were also arisen (tissues: 34.1±5.2 ng/g vs 21.6±4.7 ng/g, and 29.8± 6.8 ng/g; plasma: 5.8±0.4 ng/L vs 3.7±0.6 ng/L, and 2.9± 0.8 ng/L)(P < 0.01). The contents of Mot, SS and CCK in patients with stomach-heat were not significantly changed (P > 0.05).

CONCLUSION: The contents of Mot, SS and CCK may have important values in the clinical diagnosis and treament for patients with spleen-asthenia.

Key Words: N/A
0 引言

胃动素(Mot)、生长抑素(SS)、胆囊收缩素(CCK)是三种重要的调节胃肠运动生理功能的脑-肠肽, 可在中枢和外周的不同层面调节胃肠道的功能. 脾虚失健运时可出现一系列消化系统运动功能的障碍; "脾主运化、脾在志为思、思伤脾", 表明中医脾和脑-肠肽在功能和分布上的众多相似, 观察脾虚证患者脑-肠肽浓度的变化成为目前脾虚证本质研究的热点之一. 有关脾虚证与Mot、SS的研究报道较多, 但各家报道不尽一致[1-19]; CCK与脾虚证的研究主要为即往我们对脾虚动物模型的观察结果[21-23]. 为此本研究用RIA法测定脾气虚证患者血浆和胃窦黏膜组织中Mot、SS、CCK的浓度, 并观察补脾益气经典古方四君子汤对他们的调正作用, 拟探讨Mot、SS和CCK的浓度变化对脾气虚证临床辨证施治的意义.

1 材料和方法
1.1 材料

2000-04/2003-06期间我校西京医院中医药研究中心和唐都医院消化内科门诊和住院的患者. 采用辨病与辨证结合的分型原则, 选择胃镜及西医诊断为慢性胃炎、浅表性胃炎、胃溃疡、胆汁反流性胃炎等而中医诊断为脾气虚、胃热炽盛证者, 各证辨证符合"中医虚证辨证参考标准" [24]及《中医诊断学》的诊断标准. 其中辨证符合脾气虚者32(男24、女18例), 年龄31-63(平均45±7岁); 辨证符合胃热炽盛证者30(男16、女14例), 年龄33-61(平均46±6岁). 各组间性别、年龄比较无显著差异性. 以上各组均除外糖尿病、肾病、肝病、恶性肿瘤、心血管疾病、呼衰、胰腺疾病所致的消化功能障碍患者.

1.2 中药方的组成、剂量和制备

四君子汤, 红参: 炒白术: 茯苓: 炙甘草为2: 2: 2: 1; 清胃散, 生石膏: 知母: 栀子: 黄芩: 大黄为2: 1: 1: 1: 1; 本院中药房提供; 将药物于清水中浸泡30 min, 煮沸后, 文火煎30 min, 再浓缩至5 g/mL浓度水煎液.

1.3 两组患者在经6 d洗脱后, 分别在服四君子汤和清胃散水煎液(300 mL/d)的前1 d和连续服药后的第20 d, 取晨起空腹全血5 mL, 行胃镜检查过程中取胃窦黏膜组织1-2块.

1.3.1 血浆标本的收集: (1)试管编号后预先加入10% EDTA-Na2和抑肽酶各75 ul, 置于冰箱中4 ℃预冷, 抽取静脉血后混匀; (2)低温离心, 1 500转×15 min, (2)将血浆样本按0.5 mL/管分装于玻璃试管中, -20 ℃储存备测. 组织样本的收集: 塑料试管编号, 留取后置入1.5 mL塑料炮弹管中, 立即将炮弹管液氮冻存, 后取出置于低温冰箱保存备测.

1.3.2 放射免疫法检测: 按试剂盒说明书进行.125Ⅰ-胃动素放免分析试剂盒: 东亚免疫研究所(中国人民解放军总医院, 北京), 批号: 0133; 125Ⅰ-生长抑素放免分析试剂盒: 北京海科锐生物技术中心, 批号: 0104; 125Ⅰ-胆囊收缩素放免分析试剂盒: 上海第二军医大学神经生物教研室.

2 结果
2.1 胃动素放免分析结果

服药前脾气虚组(Spleen-Asthenia, SA)血浆及组织中的Mot含量较胃热组(Stomach-Heat)显著降低(P<0.01), 服四君子汤后, 血浆及组织中的Mot含量明显升高, 而胃热炽盛者服药前后Mot含量无显著变化(P>0.05), 见表1.

表1 各组患者血浆及胃窦组织中胃动素含量比较.
Groupngastric antrum
nplasma
前后前后
SA31109.4±18.9a183.0±23.9d3261.7±10.6a126.3±24.6d
SH28219.8±25.3202.1±27.130171.4±30.8159.2±44.6c
aP<0.01 vs SH;
cP<0.05,
dP<0.01 vs SA.
2.2 生长抑素放免分析结果

脾气虚组血浆及组织中的SS含量较胃热组显著升高(P<0.01); 服四君子汤后, 血浆及组织中的SS含量明显降低(P<0.01), 而胃热炽盛者服药前后SS含量无显著变化(P>0.05), 见表2.

表2 各组患者血浆及胃窦组织中生长抑素含量.
Groupngastric antrum
nplasma
前后前后
SA30224.3±67.9a114.2±34.5d3274.5±17.2a40.1±12.7d
SH2680.2±25.685.4±19.73030.3±11.832.73±12.4
aP<0.01 vs SH;
dP<0.01 vs SA.
2.3 CCK放免分析结果

脾气虚组血浆及组织中的CCK含量较胃热组显著升高(P<0.01); 脾气虚组服药后, 血浆及组织中的CCK含量明显降低(P<0.01), 而胃热炽盛者服药前后CCK含量无显著变化(P>0.05), 见表3.

表3 各组患者血浆及胃窦组织中CCK含量.
Groupngastric antrum
nplasma
前后前后
SA3234.1±5.2a29.8±6.8c325.8±0.4a8.3±0.7d
SH3021.6±4.727.5±3.9303.7±0.64.9±0.8
aP<0.01 vs SH;
cP<0.05,
dP<0.01 vs SA.
3 讨论

1993年我们的临床研究发现[1]: 脾虚泄泻患者血浆和十二指肠降段黏膜组织中Mot含量显著低于非脾虚泄泻组. 2000[22,25]年我们观察了利血平致短期(利血平作用7 d)和长期(利血平作用14 d)脾虚大鼠模型血浆及胃窦、十二指肠球部和空肠组织的Mot、SS和CCK含量及其内分泌细胞变化, 以及四君子汤的调正作用: (14 d利血平脾虚大鼠Mot的含量(血浆及组织)明显下降(P<0.05), 而SS和CCK在血浆及组织中的含量却升高(P<0.01). 本研究在上述研究基础上进一步观察了脾气虚证患者血浆和胃窦组织中Mot、SS和CCK含量的变化及四君子汤的调正作用, 表明: 比较胃热组, 脾虚证患者血浆和胃窦黏膜组织中的Mot、SS和CCK含量变化与14 d利血平脾虚大鼠Mot、SS和CCK在血浆及组织中的含量变化趋势一致; 四君子汤20 d作用后, 患者在自觉症状改善的同时, Mot、SS和CCK三激素的含量较治疗前有显著变化.

有关这方面的研究, 其他学者也有大量的报道. 如: 毛炯et al[4]研究发现脾气虚、脾阴虚患者血浆Mot水平均显著增高, 且脾阴虚组显著低于脾气虚组; 贾波et al[5]采用大黄苦寒泻下法复制大鼠脾虚模型, 其血浆中胃动素含量明显降低(P<0.01); 马建伟et al[4]研究发现大鼠脾虚模型血浆、胃窦组织及结肠组织中SS含量显著升高, 经治疗后SS含量较自然恢复组明显减少, 提示SS含量升高可能是脾虚证的病理基础之一; 而智发朝et al[7]发现脾虚症患者胃窦黏膜SS含量明显降低, 血浆SS含量无明显变化; 张万岱et al[14-16]报道脾虚证大鼠胃窦黏膜、十二指肠中SS增多.

已知胃动素对胃肠运动和胃肠电活动都有强烈的影响: 对胃体、胃窦及幽门不同区域肌细胞均有明显收缩作用, 可促进胃排空, 刺激胃蛋白酶分泌, 使胃黏膜血流增加但不增加胃酸分泌, 可诱发胃强烈收缩和小肠明显的分节运动, 对胃肠内容起清扫作用. 此外胃动素还可影响胆囊收缩运动及刺激胃蛋白酶和胰液的分泌. SS在体内生理作用主要是对神经传递、腺体分泌、平滑肌收缩和细胞增生的广泛抑制. 他抑制几乎所有已知内、外分泌, 如生长激素, 胰岛素、CCK、Mot、甲状腺素、胃蛋白酶、胰蛋白酶、胰多肽、胃酸、胰外分泌之重碳酸盐等; 抑制胃、肠、胆系收缩; 延长胃肠通过时间[26-30]. CCK主要作用方式为内分泌和腔分泌, 其浓度的升高可抑制胃肠电活动、胃酸分泌及胃排空, 中枢CCK浓度的升高可抑制食欲. CCK在肠道运动中主要抑制近端十二指肠蠕动, 促进远端十二指肠和空肠蠕动, 使近端, 远端结肠收缩[30-31].

由此我们推测: 脾气虚之"脾失健运"的病理生理基础与Mot、SS和CCK三激素在血浆和组织中的含量变化密切相关. Mot不足, CCK升高, 以及SS含量增加致抑制胃肠激素释放的作用加强, 均能较好地解释"脾失健运"患者出现的纳差、腹胀、早饱和大便异常等症状. 四君子汤对这三激素具有一定的调正作用. 故Mot、SS和CCK的浓度变化对脾气虚"脾失健运"的临床辨证施治可能有重要的参考价值. 只是有关这方面的工作值得进一步进行, 如增设健康对照组并规范阳性对照组、加大样本量、拓宽观察证型和疾病种类等.

编辑: N/A

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