氨溶液对肝硬化大鼠胃黏膜的影响及香叶基香叶基丙酮的治疗作用。

Sugimoto M, Machida Y, Ito K

Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.

J Gastroenterol Hepatol. 1999 Jun;14(6):529-33. doi: 10.1046/j.1440-1746.1999.01910.x.

BACKGROUND

We designed an animal model in order to clarify whether Helicobacter pylori infection causes the gastric mucosal lesion frequently seen in cirrhotic patients.

METHODS

Ammonia (NH3) solution was given to rats with carbon tetrachloride-induced cirrhosis. The gastric mucosal hexosamine (Hx) content and histopathological findings in the cirrhotic rats were analysed and compared with those of the intact liver rats. Moreover, the usefulness of geranylgeranylacetone (GGA) was investigated in both rat groups. Both rat groups were subdivided according to the treatment as follows: a control group, an NH3 (0.02% solution) group, and an NH3 + GGA (400 mg/kg per day) group; and fed for 4 weeks.

RESULTS

The gastric mucosal Hx content of the control group of the cirrhotic rats (16.7 +/- 5.2 microg/mg) was significantly lower than that of the control group of the intact liver rats (26.6 +/- 4.5 microg/mg, P < 0.05). In the cirrhotic rats, the Hx content of both the NH3 (31.9 +/- 13.1 microg/mg) and the NH3 + GGA group (31.9 +/- 9.8 microg/mg) was significantly higher than the Hx content of the control group (P < 0.05). Microscopically, in the cirrhotic rats, while scattered mucosal erosions were recognized in three of five rats of the NH3 group, there were no erosions in any rats of the NH3 + GGA group.

CONCLUSIONS

These data suggest that the gastric mucosal defence mechanism is defective in liver cirrhosis and that NH3 enhances this defensive mechanism by acting as mild irritant; however, in some cirrhotics this results in gastric erosion due to excessive irritation. Geranylgeranylacetone protects the gastric mucosa against NH3 irritation in cirrhotics without enhancing the Hx content. Thus, H. pylori infection may be a possible cause of the gastric mucosal lesion in patients with liver cirrhosis. The mechanism of the therapeutic effect of GGA is not due to an enhancement of the gastric mucosal Hx content.

背景

我们设计了一种动物模型，以阐明幽门螺杆菌感染是否会导致肝硬化患者常见的胃黏膜病变。

方法

给四氯化碳诱导肝硬化的大鼠给予氨（NH₃）溶液。分析并比较肝硬化大鼠的胃黏膜己糖胺（Hx）含量和组织病理学结果与正常肝脏大鼠的情况。此外，还研究了香叶基香叶基丙酮（GGA）在两组大鼠中的作用。两组大鼠均根据治疗情况细分为：对照组、NH₃（0.02%溶液）组和NH₃ + GGA（每天400 mg/kg）组；并喂养4周。

结果

肝硬化大鼠对照组的胃黏膜Hx含量（16.7±5.2微克/毫克）显著低于正常肝脏大鼠对照组（26.6±4.5微克/毫克，P<0.05）。在肝硬化大鼠中，NH₃组（31.9±13.1微克/毫克）和NH₃ + GGA组（31.9±9.8微克/毫克）的Hx含量均显著高于对照组（P<0.05）。显微镜下，在肝硬化大鼠中，NH₃组五只大鼠中有三只出现散在的黏膜糜烂，而NH₃ + GGA组的任何大鼠均未出现糜烂。

结论

这些数据表明，肝硬化时胃黏膜防御机制存在缺陷，NH₃作为轻度刺激物可增强这种防御机制；然而，在一些肝硬化患者中，这会因过度刺激而导致胃糜烂。香叶基香叶基丙酮可保护肝硬化患者的胃黏膜免受NH₃刺激，而不会提高Hx含量。因此，幽门螺杆菌感染可能是肝硬化患者胃黏膜病变的一个可能原因。GGA治疗作用的机制并非由于胃黏膜Hx含量的增加。