一氧化氮与唾液腺表皮生长因子在调节大鼠胃黏膜完整性中的相互作用。

Interaction of nitric oxide and salivary gland epidermal growth factor in the modulation of rat gastric mucosal integrity.

作者信息

Tepperman B L, Soper B D

机构信息

Department of Physiology, Faculty of Medicine, University of Western Ontario, London, Canada.

出版信息

Br J Pharmacol. 1993 Sep;110(1):229-34. doi: 10.1111/j.1476-5381.1993.tb13797.x.

DOI:10.1111/j.1476-5381.1993.tb13797.x

PMID:7693280

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2175994/

Abstract

The interaction between endogenous nitric oxide (NO) and factors from the rat submandibular salivary gland such as epidermal growth factor (EGF) on gastric mucosal integrity in the rat has been investigated. 2. Bolus administration of the NO synthase inhibitor, NG nitro-L-arginine methyl ester (L-NAME; 6.25-50 mg kg-1, i.v.) to animals treated intraluminally with 0.15 N HCl resulted in a significant increase in the area of mucosal haemorrhagic damage at doses 12.5 and 50 mg kg-1. Concurrent administration of indomethacin (5 mg kg-1, i.v.) resulted in a significant haemorrhagic mucosal damage in response to L-NAME (12.5-50 mg kg-1). Administration of the highest dose of L-NAME resulted in an increase in histological damage to the rat gastric mucosa. 3. When compared to control animals, the extent of damage produced by L-NAME or L-NAME in combination with indomethacin was significantly exacerbated in rats which had been sialoadenectomized (SALX) by removal of the submandibular salivary glands. The mucosal damage in SALX rats was ameliorated by treatment with EGF (5 and 10 micrograms kg-1, i.v.). 4. L-NAME administration resulted in a small reduction of gastric mucosal blood flow as assessed by laser Doppler flowmetry (LDF). The reduction in LDF by 25 and 50 mg kg-1 L-NAME was significantly greater in SALX rats than in rats with intact salivary glands. Pretreatment of SALX rats with indomethacin did not augment this large decrease in LDF suggesting that endogenous prostanoids do not interact with NO and salivary factors in regulating mucosal microcirculation. 5. Mucosal NO biosynthesis as assessed by ['4C]-citrulline formation was reduced in SALX rats when compared to control animals. Pretreatment of SALX animals with parenterally-administered EGF(10 microg kg-1) was associated with an increase in [14C]-citrulline formation in the gastric mucosa to levels observed in control SALX rats.6. These data suggest that factors which originate from the salivary gland such as EGF interact with NO in the maintenance of mucosal integrity. The effects may be mediated at least in part by changes in gastric mucosal blood flow. Salivary glands and EGF may mediate these effects to some extent via changes in mucosal NO biosynthesis.

摘要

研究了内源性一氧化氮（NO）与大鼠下颌下唾液腺产生的诸如表皮生长因子（EGF）等因子对大鼠胃黏膜完整性的相互作用。2. 给经腔内注射0.15 N盐酸处理的动物静脉推注一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME；6.25 - 50 mg/kg，静脉注射），剂量为12.5和50 mg/kg时，黏膜出血损伤面积显著增加。同时静脉注射吲哚美辛（5 mg/kg）会导致对L-NAME（12.5 - 50 mg/kg）产生显著的出血性黏膜损伤。给予最高剂量的L-NAME会导致大鼠胃黏膜组织学损伤增加。3. 与对照动物相比，通过切除下颌下唾液腺进行涎腺切除（SALX）的大鼠，L-NAME或L-NAME与吲哚美辛联合产生的损伤程度显著加重。用EGF（5和10 μg/kg，静脉注射）治疗可改善SALX大鼠的黏膜损伤。4. 通过激光多普勒血流仪（LDF）评估，给予L-NAME会使胃黏膜血流量略有减少。25和50 mg/kg的L-NAME导致的LDF降低在SALX大鼠中比在唾液腺完整的大鼠中显著更大。用吲哚美辛预处理SALX大鼠并未增强LDF的大幅下降，这表明内源性前列腺素在调节黏膜微循环中不与NO和唾液因子相互作用。5. 与对照动物相比，通过[¹⁴C]-瓜氨酸形成评估的SALX大鼠黏膜NO生物合成减少。用胃肠外给予的EGF（10 μg/kg）预处理SALX动物与胃黏膜中[¹⁴C]-瓜氨酸形成增加至对照SALX大鼠中观察到的水平相关。6. 这些数据表明，诸如EGF等源自唾液腺的因子在维持黏膜完整性方面与NO相互作用。这些作用可能至少部分是由胃黏膜血流量的变化介导的。唾液腺和EGF可能在一定程度上通过黏膜NO生物合成的变化介导这些作用。