Role of thromboxane A2 in healing of gastric ulcers in rats
Role of thromboxane A2 in healing of gastric ulcers in rats
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DOI：
10.1254/jjp.79.101
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Okabe, S
中科院分区：
文献类型：
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作者：
Takahashi, S;Shigeta, J;Okabe, S
本文研究了血栓素A（TX）2在大鼠胃溃疡愈合中的作用。在雄性Donryu大鼠中产生乙酸溃疡。与正常大鼠胃粘膜相比，溃疡组织中TXA（2）的合成显著增加，而完整组织中TXA（2）的合成无明显变化。吲哚美辛抑制溃疡组织中血栓素A（2）和前列腺素E-2（PGE-2）的合成，而NS-398（选择性环氧合酶-2抑制剂）仅减少PGE-2的合成。OKY-046（TXA（2）合成酶抑制剂）仅剂量相关地抑制TXA（2）合成。OKY-046的最大作用（80%抑制）在大于30 mg/kg时被发现。当给予OKY-046 14天时，超过30 mg/kg的药物显著加速溃疡愈合，而不影响酸分泌。与对照组相比，OKY-046的溃疡面积最大减少约30%。组织学研究显示，OKY-046显著促进粘膜的再生，但溃疡基底的成熟和基底中的血管生成均不受影响。OKY-046和TXB 2对培养的大鼠胃上皮细胞的增殖没有影响，但U-46619（TXA（2）模拟物）剂量相关地抑制增殖，而不降低细胞活力。这些结果表明，增加的TXA（2），可能来自溃疡组织中的环氧合酶-1，对大鼠溃疡愈合产生微弱的抑制作用。TXA（2）的作用可能部分是由于阻止溃疡边缘的胃上皮细胞增殖。
We investigated the role of thromboxane (TX) A(2) in gastric ulcer healing in rats. Acetic acid ulcers were produced in male Donryu rats. TXA(2) synthesis in the stomachs with ulcers was significantly elevated in ulcerated tissue, but not in intact tissue, compared with that in the gastric mucosa of normal rats. Indomethacin inhibited both TXA(2) and prostaglandin E-2 (PGE(2)) synthesis in ulcerated tissue, while NS-398 (selective cyclooxygenase-2 inhibitor) reduced only PGE(2) synthesis. OKY-046 (TXA(2) synthase inhibitor) dose-relatedly inhibited only TXA(2) synthesis. The maximal effect of OKY-046 (80% inhibition) was found at more than 30 mg/kg. When OKY-046 was administered for 14 days, the drug at more than 30 mg/kg significantly accelerated ulcer healing without affecting acid secretion. The maximal reduction of ulcerated area by OKY-046 was about 30%, compared with the area in the control. Histological studies revealed that regeneration of the mucosa was significantly promoted by OKY-046, but neither maturation of the ulcer base nor angiogenesis in the base were affected. OKY-046 and TXB2 had no effect on proliferation of cultured rat gastric epithelial cells, but U-46619 (TXA(2) mimetic) dose-relatedly prevented the proliferation without reducing cell viability. These results indicate that the increased TXA(2), probably derived from cyclooxygenase-1 in ulcerated tissue, exerts a weak inhibitory effect on ulcer healing in rats. The effect of TXA(2) might be due partly to prevention of gastric epithelial cell proliferation at the ulcer margin.