MOLECULAR MECHANISM OF INFLAMMATORY AND IMMUNOLOGICAL FACTORS INVOLVED IN DRUG-INDUCED LIVER INJURY

药物性肝损伤中炎症和免疫因素的分子机制

• 批准号: 09672209
• 负责人: HOJO Hiroshi
• 金额: $ 1.92万
• 依托单位: Showa Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672209/
• 关键词: Liver injury; carbon tetracloride; interleukin-6; cytokine; rat; dexamethasone; インターロイキン6; デキサメサゾン; エンドトキシン

We have investigated the role of inflammatory and immune mediators in the carbon tetrachloride induced liver injury models. An administration of carbon tetrachloride through the subcutaneous (s.c.) or intraperitoneal (I.p.) route induced interleukln-6 (IL-6) in plasma with a peak at 8 and 4 hr later, respectively, but that through the per os (p.s.) route did not. The maker hepatic enzyme activities were increased with a peak 24 hr to 48 hr after carbon tetrachloride administration, however, the rate of increase was higher through the p.o. route than through the s.c. or I.p. route. As ratios of the vehicle (corn oil) to carbon tetrachloride were increased, the IL-6 induction was decreased and the leak of hepatic enzymes was augmented. Pretreatment with dexamethasone markedly suppressed the IL-6 induction and enhanced the enzyme leaks in the rats treated with carbon tetrachloride through the s.c. or I.p. route.These results represent the close reverse correlation between IL-6 induction and liver injury, suggesting the IL-6 induced in the early phase after carbon tetrachloride might play a suppressive role in the development of the liver injury.

我们研究了炎症和免疫介质在四氯化碳诱导的肝损伤模型中的作用。通过皮下注射四氯化碳(S.C.)或腹腔内注射(Ip)。白介素6(IL-6)诱导后8h和4h达高峰，但通过口服途径达到高峰(P.S.)路由没有。在四氯化碳染毒后24小时至48小时，血清标志物肝酶活性均有升高，且升高的速度更快。而不是通过南卡罗来纳州。或者IP。路线。随着助剂(玉米油)与四氯化碳比例的增加，IL-6的诱生作用降低，肝酶漏出增加。地塞米松可显著抑制四氯化碳诱导的IL-6的产生，增加经皮下注射四氯化碳的大鼠的酶渗漏。或者IP。这些结果表明IL-6的诱导与肝损伤之间存在密切的负相关关系，提示四氯化碳后早期诱导的IL-6可能在肝损伤的发生发展中起抑制作用。