磺糖酯对消炎痛诱导的胃黏膜损伤相关凋亡过程的影响。

Effect of sulglycotide on the apoptotic processes associated with indomethacin-induced gastric mucosal injury.

机构信息

Research Center, University of Medicine and Dentistry of New Jersey, 07103-2400, Newark, NJ, USA.

出版信息

Inflammopharmacology. 1998;6(3):243-53. doi: 10.1007/s10787-998-0023-3.

DOI:10.1007/s10787-998-0023-3

PMID:17657623

Abstract

AIMS

In this study we investigated the effect of the antiulcer agent, sulglycotide, on the activity of a key pro-apoptotic protease, caspase-3, and the expression of inducible nitric oxide synthase (NOS-2) associated with gastric epithelial cell apoptosis triggered by the enhancement in tumour necrosis factor-alpha (TNF-alpha) during indomethacin-induced gastric mucosal injury.

METHODS

The experiments were conducted with rats pretreated intragastrically with sulglycotide (200 mg/kg) or vehicle, followed 30 min later by an intragastric dose of indomethacin (60 mg/kg). The animals were killed 2 h later and their mucosal tissue used for macroscopic assessment, assays of epithelial cell apoptosis and TNF-alpha, and the measurement of caspase-3 and NOS-2 activities.

RESULTS

In the absence of sulglycotide, indomethacin caused multiple haemorrhagic lesions accompanied by a 20-fold enhancement in gastric epithelial cell apoptosis and a 47% increase in mucosal expression of TNF-alpha, while NOS-2 showed an 11.9-fold induction and the activity of caspase-3 increased 3.9-fold. Pretreatment with sulglycotide produced a 51.2% reduction in the extent of mucosal damage caused by indomethacin, a 43.9% decrease in the epithelial cell apoptosis and a 39.7% reduction in TNF-alpha, while the activity of caspase-3 decreased by 58.8% and that of NOS-2 showed a 47.3% decline.

CONCLUSIONS

Our findings implicate the enhanced expression of caspase-3 and NOS-2 in the process of death signalling cascade associated with indomethacin-induced gastric mucosal injury, and show that sulglycotide is capable of suppressing the pathway of apoptotic events propagated by TNF-alpha, NOS-2 and caspase-3.

摘要

目的

本研究旨在探讨抗溃疡剂硫糖酯对肿瘤坏死因子-α（TNF-α）增强诱导的胃上皮细胞凋亡过程中关键促凋亡蛋白酶 caspase-3 活性和诱导型一氧化氮合酶（NOS-2）表达的影响。

方法

采用大鼠模型，大鼠预先给予硫糖酯（200mg/kg）或载体灌胃，30 分钟后给予吲哚美辛（60mg/kg）灌胃。2 小时后处死动物，取胃黏膜组织进行大体评估、上皮细胞凋亡和 TNF-α检测，并测定 caspase-3 和 NOS-2 活性。

结果

在没有硫糖酯的情况下，吲哚美辛导致多个出血性病变，同时胃上皮细胞凋亡增加 20 倍，黏膜 TNF-α表达增加 47%，NOS-2 诱导增加 11.9 倍，caspase-3 活性增加 3.9 倍。硫糖酯预处理使吲哚美辛引起的黏膜损伤程度减少 51.2%，上皮细胞凋亡减少 43.9%，TNF-α减少 39.7%，同时 caspase-3 活性减少 58.8%，NOS-2 活性减少 47.3%。