| 抄録 |
Hydrogen sulfide（H2S）is a gaseous mediator produced throughout the gastrointestinal tract and by many species of commensal and infectious bacteria. Like nitric oxide and prostaglandins, H2S is an important mediator of mucosal defence；that is, suppression of its synthesis leads to increased susceptibility to ulceration. On the other hand, administration of H2S donors, including compounds derived from garlic, can greatly increase the resistance of the mucosa to injury induced by nonsteroidal anti-inflammatory drugs or ischemia-reperfusion injury. H2S also exerts a number of anti-inflammatory effects, including inhibition of leukocyte adherence to the vascular endothelium. Chronic suppression of H2S synthesis leads to a significant increase in the‘basal’level of inflammation in the digestive tract, as well as decreased cyclooxygenase-2 expression and prostaglandin synthesis. When inflamed or injured, a marked increase in the capacity of gastrointestinal tissue to synthesize H2S is observed. There is convincing evidence that in such circumstances, H2S contributes significantly to promoting the healing of the damaged tissue and to resolution of the inflammatory response. Thus, inhibition of H2S synthesis results in significant delays in ulcer healing and exacerbation of tissue inflammation. Administration of H2S donors accelerates healing of ulcers. The ability of H2S to enhance mucosal defence, healing and resolution of inflammation has been exploited in the development of several novel anti-inflammatory drugs. H2S-releasing derivatives of mesalamine have been shown to exert markedly enhanced anti-inflammatory effects, compared to the parent drug, in models of colitis. One of the key mechanisms for the enhanced anti-inflammatory activity appears to be suppression of pro-inflammatory cytokine production. H2S-releasing derivatives of cyclooxygenase inhibitors exhibit comparable anti-inflammatory activity to the parent drugs, but with markedly reduced injurious effects in the digestive tract. These drugs show considerable promise for treatment of chronic inflammatory diseases, such as osteoarthritis, with greatly reduced gastrointestinal toxicity as compared to existing therapies. |
