脂多醣體對於
Pentagastrin 誘導胃酸分泌的作用：經由一氧化氮與
第一型遲緩激 基因表現之探討
Effect of Lipopolysaccharide on Pentagastrin-induced
Gastric Acid Secretion：Involvement of Nitric Oxide and
Bradykinin B1 mRNA
中文摘要
脂多醣體(Lipopolysaccharide；LPS)又名內毒素(endotoxin)，係來自革蘭氏
陰性桿菌細胞壁之具有毒性磷酸化醣脂質的衍生物。本研究的目的是探討
LPS
在胃內所扮演的角色，及其參與胃酸分泌的作用機轉，同時並探討一氧化氮及第
一型遲緩激 受體基因表現(bradykinin B1 mRNA)的情形。
結果顯示：LPS (mg/kg)可以抑制經由合成胃泌素(8 mg /kg/h)誘發胃酸分泌
作用，此抑制作用可被[Des-Arg10] HOE 140, (H-158, 20 mg/kg)第一型
遲緩激 受體的拮抗劑,或 L- NG-nitro arginine methyl ester (L-NAME) (5
mg/kg)一氧化氮合成 抑制劑所拮抗。而靜脈注射 LPS (1 mg/kg)可明顯抑
制自發性胃酸分泌之作用，但
L-NAME (5 mg/kg)可顯著增加自發性胃酸分泌
的作用。H-158 (20 mg/kg)則對於自發性胃酸分泌的作用沒有影響，但對血
液中一氧化氮含量則有顯著的減少。測量血液中一氧化氮含量顯示
LPS 對於合
成胃泌素誘導酸分泌確可增加血漿中一氧化氮含量約兩倍左右。進一步利用西方
墨點法 (Western blot)進行誘導性一氧化氮合成 (induced nitric oxide
synthase；iNOS)蛋白質的表現，結果顯示 LPS 可隨劑量依存性及時間依存性
增加誘導性一氧化氮合成 。更進一步利用反轉錄聚合 連鎖反應(Reverse
Transcription Polymerase Chain Reaction；RT-PCR)的結果顯示，在胃部
Bradykinin B1 mRNA 之表現亦是隨著時間變化或劑量依存性而增加。
綜觀上述結果
LPS 在胃部的作用是抑制自發性胃酸分泌及合成胃泌素誘導胃酸
分泌之作用，此一機轉可能經由一氧化氮的產生及
bradykinin B1 mRNA 表現
來參與調控。
關鍵詞：脂多醣體、合成胃泌素、一氧化氮、遲緩激 、誘導性一氧化氮合成 、
第一型遲緩激 受體基因表現、西方墨點法、反轉錄聚合 連鎖反應
英文摘要
Lipopolysaccharides (LPS), also termed endotoxins, are a family of toxic phosphorylated glycolipids derived from the cell envelope of gram—negative bacteria. In the present study, we attempted to evaluate the effects of LPS on gastric acid secretion：involvement of nitric oxide and bradykinin B1 mRNA. LPS (1
mg/kg) reduced pentagastrin (8 mg/kg/h)-stimulated gastric acid secretion. The inhibitory effect of LPS on pentagastrin stimulated gastric acid secretion was blocked by a potent bradykinin B1 receptor antagonist, [Des-Arg10] HOE 140 (H-158) of 20 mg/kg, or a NO synthase (NOS) inhibitor, NG-nitro arginine methyl ester, L-NAME of 5 mg/kg. LPS significantly decreased spontaneous acid secretion, but L-NAME (5 mg/kg) significantly increased the spontaneous acid secretion. H-158 did not affect the spontaneous acid secretion. H-158 was found to decrease plasma NO in spontaneous acid secretion. LPS was found to increase plasma NO production by two folds while LPS decreased pentagastrin-stimulated acid secretion. Furthermore, Western blot and RT-PCR were performed for iNOS protein and bradykinin B1 gene expression, respectively. LPS-treatment increased iNOS protein and bradykinin B1 mRNA in stomachs in a dose-dependent manner. These results suggest that LPS suppressed pentagastrin stimulated acid secretion via the
production of NO. NO might play an important role in the regulation of acid secretion at least by an involvement of bradykinin B1 receptors.
Key words：Lipopolysaccharide；pentagastrin；nitric oxide；bradykinin；induced nitric oxide synthase ；B1 bradykinin receptor；western blot ；RT-PCR
