临床研究 Open Access
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
世界华人消化杂志. 2003-08-15; 11(8): 1230-1233
在线出版日期: 2003-08-15. doi: 10.11569/wcjd.v11.i8.1230
肝硬化患者血浆胃动素、胆囊收缩素、生长抑素及其胃电的改变
张蓉, 闻勤生, 黄裕新, 赵海峰, 田力
张蓉, 闻勤生, 黄裕新, 赵海峰, 田力, 中国人民解放军第四军医大学唐都医院消化内科 陕西省西安市 710038
张蓉, 女, 1970-05-17生, 贵州省贵阳市人, 汉族, 主治医师, 讲师.
基金项目: 全军归国人员科研启动基金资助课题, No. 6008.
通讯作者: 闻勤生, 710038, 陕西省西安市, 中国人民解放军第四军医大学唐都医院消化内科. zhangrong517@yahoo.com.cn
电话: 029-3377721 传真: 029-3377597
收稿日期: 2003-01-03
修回日期: 2003-01-20
接受日期: 2003-02-18
在线出版日期: 2003-08-15

目的

通过测定肝硬化患者血浆胃动素(MTL)、胆囊收缩素(CCK)、生长抑素(SS)及其胃电的变化, 探讨肝硬化患者胃肠功能障碍的主要机制.

方法

应用放免法分别测定38例肝硬化患者和30名健康志愿者空腹血浆MTL、CCK及SS4浓度. 采用美国3CPM胃电图仪观察所有入选者水负荷试验前后胃肌电活动情况, 观察指标包括频率百分比、主频、餐后和餐前功率比以及运行性频谱分析.

结果

肝硬化患者MTL, CCK水平较对照组明显升高(287±81 ng/L, 3.3±1.4 ng/L vs 131±27 ng/L, 1.1±0.5 ng/L; P<0.01, t = 11.150, n =38; P<0.01, t = 9.146, n = 38), 且不同肝功能状态时MTL、CCK水平之间差异显著(P<0.05, F = 87.570; P<0.05, F = 47.506), 呈现Child-Pugh C级>B级>A级的趋势. 血浆SS水平在Child-Pugh B级和C级患者明显升高, 与对照组差异显著(67±10 ng/L vs 28±13 ng/L; P<0.01, t = 7.652, n = 16; P<0.01, t = 9.428, n = 12), 而在Child-Pugh A级患者升高不明显. 同时, Child-Pugh B级, C级患者胃电节律紊乱率明显高于对照组(P<0.01, t = -8.088, n =16; P<0.01, t = 7.697, n = 16; P<0.01, t = -10.178, n = 12; P<0.01, t = 9.817, n = 12), 主频(P<0.01, t = -7.575, n = 16; P<0.01, t = -11.623, n = 12)、餐后和餐前功率比(P<0.01, t = -3.987, n = 16; P<0.01, t = -4.330, n = 12)低于对照组, 差异显著.

结论

肝硬化患者胃电节律紊乱百分比较正常人明显升高. 胃肠激素的变化是肝硬化患者胃运动功能障碍的重要原因之一.

关键词: N/A
引文著录: 张蓉, 闻勤生, 黄裕新, 赵海峰, 田力. 肝硬化患者血浆胃动素、胆囊收缩素、生长抑素及其胃电的改变. 世界华人消化杂志 2003; 11(8): 1230-1233
Plasma levels of motilin, cholecystokinin and somatostatin and gastric electrical activity in patients with liver cirrhosis
Rong Zhang, Qin-Sheng Wen, Yun-Xin Huang, Hai-Feng Zhao, Li Tian
Rong Zhang, Qin-Sheng Wen, Yun-Xin Huang, Hai-Feng Zhao, Li Tian, Department of Gastroenterology of Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.
Supported by: the Start-up Funds of Scientific Research for Returned Overseas Scholars of Chinese PLA, No. 6008.
Correspondence to: Dr. Qin-Sheng Wen, Department of Gastroenterology of Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China. Zhangrong517@yahoo.com.cn
Received: January 3, 2003
Revised: January 20, 2003
Accepted: February 18, 2003
Published online: August 15, 2003

AIM

To investigate the mechanism of gastrointestinal dysfunction in patients with liver cirrhosis (LC) by determining the plasma levels of motilin (MTL), cholecystokinin (CCK) and somatostatin (SS) and gastric electrical activity.

METHODS

Plasma levels of MTL, CCK and SS were determined with radioimmunoassay in 38 LC patients and 30 healthy volunteers. Gastric electrical activities in all the 68 subjects were observed with the electrogastrograph (3 CPM, USA) before and after water load tests. The indexes of the gastric electrical activities included the percentage of frequency, the main frequency, the ratio of power of postprandial to preprandial, and the frequency spectrum analysis.

RESULTS

Compared with those in the control group, the levels of MTL and CCK in LC patients were increased (287±81 ng/L. 3.3±1.4 ng/L vs 131±27 ng/L. 1.1±0.5 ng/L. P<0.01, t = 11.150, n = 38; P<0.01, t = 9.146, n = 38). There was a significant difference between the levels of MTL and CCK with different liver functions (P<0.05, F = 87.570; P<0.05, F = 47.506). The levels of MTL and CCK tended to increase with the liver function from Child-Pugh A to B to C. The levels of SS in LC patients with Child-Pugh B and C liver function were increased, which showed a significant difference compared with those in the control groups (67±10 ng/L vs 28±13 ng/L.P <0.01, t =7.652, n =16; P <0.01, t =9.428, n =12). But the levels of SS in the patients with Child-Pugh A were not apparently increased. At the same time, the degree of disorder of gastric electrical activity in the patients with Child-Pugh B and C of liver function was higher than that in the control group (P<0.01, t = -8.088, n = 16; P<0.01, t = 7.697, n = 16; P<0.01, t = -10.178, n = 12; P<0.01, t = 9. 817, n = 12). The main frequency (P<0.01, t = -7.575, n = 16; P <0.01, t = -11.623, n =12) and the ratio of postprandial power to preprandial power (P<0.01. t = -3.987, n = 16; P<0.01. t = -4.330, n = 12) in patients with Child-Pugh B and C of liver function were lower than that in the control group

CONCLUSION

The percentage of disorder of gastric electrical activity in LC patients is increased compared with that in healthy volunteers. The variation of the levels of gastrointestinal hormone is one of the important causes of gastrointestinal dysfunction in patients with liver cirrhosis.

Key Words: N/A
0 引言

胃肠激素主要分布在消化系统和中枢系统, 有着很广泛的生物活性. 作为全身最大脏器的肝脏, 不仅是多种胃肠激素的靶器官, 还是灭活降解许多胃肠激素的主要场所. 胃肠激素与肝纤维化和肝硬化的关系早在20 a前就有学者开始关注, 尤以MTL、血管活性肽(VIP)、SS及促胃液素/促胆囊收缩素族等的研究较多. 胃电图是利用腹部体表电极记录胃肌电活动的电信号, 通过对胃电幅值、频率百分比、主频及运行性频谱分析的研究以了解胃运动的情况. 我们测定了肝硬化患者和健康对照组空腹血浆MTL, CCK及SS水平, 同时进行餐前、餐后胃电描记, 旨在结合胃肠激素和胃电的变化趋势更加合理的解释肝硬化患者胃运动异常的一些临床表现, 为临床诊治提供理论依据.

1 材料和方法
1.1 材料

肝硬化组患者38例, 男30例, 女8例, 年龄31-70(平均45.5)岁, 诊断符合2000年西安第10次全国病毒性肝炎与肝病学术会议的标准. 其中肝炎后肝硬化34例, 酒精性肝硬化4例. 按肝功能Child-Pugh分级A级10例, B级16例, C级12例, 主要临床表现为纳差、腹胀、嗳气、上腹疼痛、恶心等症状. 无上消化道大出血、肝性脑病、肝性肾病及恶性肿瘤, 观察前1wk内未使用过抑酸剂和促胃肠道动力药物. 正常对照组30例, 男18例, 女12例, 平均年龄38.5岁, 均为1 a内无任何消化系统症状的志愿者, 肝功能及血清各型肝炎病毒标志物检测为阴性.

1.2 方法

所有入选人员均予清晨空腹抽血测定MTL, CCK及SS浓度, 检测方法采用放射免疫分析法. 检测试剂盒由海军放免中心提供, 具体操作过程严格按说明书由同一操作者进行. 采用美国3CPM公司胃电图(EGG)仪进行胃电检测. 入选者禁食一夜后, 于EGG记录开始2 h前摄入苹果汁120 ml和面包2片(总热量为837.36 kJ), 然后再禁食2 h. 进行EGG记录前应按操作说明正确放置各个电极和连接胸带, 以提高胃电信号的信噪比. 受试者置于安静环境, 避免说话、咳嗽及肢体的移动. 记录大约15 min的餐前胃电活动, 采用水负荷试验(受试者喝水至感觉胃饱)刺激胃肌电活动, 并记录30 min餐后胃电活动. 3CPM胃电图仪电脑分析系统自动打印出相关检测资料: (1)EGG信号4种频率的百分比: 过缓(1.0-2.5次/min)、正常(2.5-3.75次/min)、过速(3.75-10.0次/min)及十二指肠肌电-呼吸频段(10.0-15.0次/min); (2)运行性频谱分析; (3)某一频率段餐后和餐前功率比、主频及平均功率等.

统计学处理 数据以mean±SD表示, 两组间比较采用独立样本的t检验, 多组间比较用单因素方差分析. 采用SPSS 10.0统计包进行数据处理.

2 结果
2.1 血浆MTL, CCK及SS浓度的变化

肝硬化患者空腹血浆MTL, CCK浓度明显高于对照组(P<0.01, t = 11.150, n = 38; P<0.01, t = 9.146, n = 38). 随着肝功能的进行性减退MTL和CCK水平呈增加趋势, 且不同肝功能状态下二者浓度水平之间也存在显著差异(P<0.05, F = 87.570; P<0.05, F = 47.506), 即Child-Pugh C级>B级>A级. 血浆SS水平在Child-Pugh B, C级患者明显升高, 与对照组比较差异显著(P<0.01, t = 7.652, n = 16; P<0.01, t = 9.428, n = 12), 而在 Child-Pugh A级患者升高不明显(表1).

表1 肝硬化患者血浆MTL, CCK及SS浓度变化(mean±SD, ng/L).
分组nMTLCCKSS
Child-Pugh A级10204±22b2.4±1.0b30±9
Child-Pugh B级16285±56bd3.2±1.0bc58±12bd
Child-Pugh C级12359±74b4.4±1.3b67±10b
对照组30131±271.1±0.528±13
bP<0.01 vs对照组;
cP<0.05,
dP<0.01 vs A, C级.
2.2 胃电变化

肝硬化患者餐前、餐后正常胃电节律百分比降低, 胃动过缓节律百分比增加. 其中Child-Pugh B, C级患者二者的变化与对照组比较差异显著(P<0.01, t = -8.088, n = 16; P<0.01, t = 7.697, n = 16; P<0.01, t = -10.178, n = 12; P<0.01, t = 9. 817, n = 12). 而Child-Pugh A级患者的变化不显著. Child-Pugh C级患者餐后胃动过速百分比增加, 与对照组比较差异显著(P =<0.01). Child-Pugh B, C级患者餐前、餐后的主频均低于对照组(P<0.01, t = -7.575, n = 16; P<0.01, t = -11.623, n = 12), 餐后和餐前功率比下降, 与对照组比较差异显著(P<0.01, t = -3.987, n = 16; P <0.01, t = -4.330, n = 12)(表2).

表2 肝硬化患者胃电各指标变化(mean±SD).
分组n餐前
餐后
餐后/餐前功率
正常(%)过缓(%)过速(%)主频正常(%)过缓(%)过速(%)主频
A1054.5±11.332.1±9.010.0±7.82.9±0.658.8±14.227.4±8.510.2±8.62.8±0.54.9±3.8
B1636.5±5.4b49.3±9.2b10.9±7.32.0±0.5b33.9±9.9b52.3±13.6b9.9±9.21.9±0.4b0.9±0.8b
C1229.8±10.5b56.8±32.7b9.9±9.81.5±0.4b20.4±13.2b56.8±10.1b19.6±4.9b1.4±0.3b0.5±0.5b
D3056.8±12.830.3±11.110.4±3.23.1±0.461.8±11.325.1±12.39.9±6.43.0±0.45.3±6.5
bP <0.01 vs D (对照组).
3 讨论

肝硬化患者存在消化功能的减退及胃动力障碍, 表现为上腹饱胀、嗳气、恶心及呕吐等症状[1-3]. 大多数研究表明, 肝硬化患者存在餐后胃窦动力异常, 胃固体和液体排空延迟[4]. 由于已知消化道的正常胃肌电活动受肌肉特性、神经及胃肠激素等多种因素调节, 因此许多学者在观察到肝硬化患者胃动力异常的同时研究了多种胃肠激素的变化, 发现肝硬化时血浆中多种肽类激素浓度均升高[5,6]. 我们测定了肝硬化患者血浆MTL, CCK及SS浓度较对照组升高, 与多数文献报道一致. MTL是消化间期的调节激素, 诱发MMCIII相胃的强烈收缩和小肠分节运动, 在胃肠道起着"清道夫"的作用, 同时促进胃窦、幽门、小肠和胆道运动的协调性[7-10]. 肝硬化时由于肝脏灭活能力和肾脏排泄功能下降、侧枝循环的作用以及因胃肠道瘀血水肿, 消化间期胃肠动力减低, 胃动素反馈性分泌增加而使血浆MTL升高. 但高浓度MTL并未发挥正常的生理功能, 推测与胃肠壁上MTL受体减少, 对MTL敏感性降低有关[11]. CCK对胃运动调节有生理性意义, 有文献报道: 生理浓度的CCK对餐后胃运动有抑制作用, 从而延缓胃排空[12,13]. SS对胃肠道内分泌、外分泌、小肠的吸收和运动具有广泛作用, 对多种胃肠道激素分泌具有抑制作用, 他能抑制MTL的释放, 使MTL刺激胃内固体食物排空受影响从而抑制胃排空[14,15]. 肝硬化时CCK及SS浓度升高, 其升高的原因也与激素灭活减少、侧枝循环作用等有关[5,6,16]. 在本实验中Child A级患者血浆SS水平升高不明显, 推测是与样本较小有关系. 研究表明, 胃排空的动力是胃的收缩活动, 胃十二指肠连接部的协调运动是胃排空的生理基础. 正常胃电节律的破坏不仅影响胃的收缩, 而且影响胃肠道不同部位收缩在时间和空间上的协调性, 从而导致胃排空延迟. EGG是检测胃肌电活动的一种体表非创伤性方法, 他能反映胃肌电活动的节律和振幅变化. EGG的主频可反映胃的慢波频率, 决定着胃的最大收缩频率, 餐前餐后振幅的相对变化与胃的收缩有关, 而餐后餐前功率比反映是餐后的胃动力. 所以正常的胃电节律与正常胃动力有关, 胃电节律紊乱与胃动力障碍有较好的相关性, 甚至可作为胃排空的一项有用的间接预测指标[17-23]. 本实验显示肝硬化患者胃电节律紊乱百分比较正常人高, 且肝功能愈差的患者, 其胃电节律紊乱发生率愈高. 我们观察到随着肝硬化患者胃动过缓百分比的增加, 其主频多介于1-2.5 cpm, 而餐后餐前功率比较对照组明显减少, 提示肝硬化患者尤以Child B, C级患者餐后胃排空能力明显下降, 这与大多数文献报道一致. 肝硬化患者胃电节律紊乱发生的机制[24-31]: (1)肝功能受损后胆红素排泄障碍、各类激素灭活减少; (2)门脉高压导致胃肠道长期淤血缺氧, 胃肠道平滑肌间神经元功能受阻, 直接影响神经递质的传递; (3)肝硬化内毒素血症, 血清中NO浓度升高导致胃排空延缓; (4)肝硬化患者易发生水、电解质紊乱从而影响胃肠道平滑肌的电生理特性也是原因之一.

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