競技運動學系2018-04-162025-07-272018-04-162018-04-16https://ir.ntus.edu.tw/handle/987654321/237計畫編號：NSC95-2320-B028-001-MY2 研究期間：2006/08/01~2008/07/31接受過器官移植的病人必須服用免疫抑制劑以控制病情，由於金絲桃草(St. John，s Wort)與環孢靈（Cyclosporine）倂用後產生急性器官排斥，引起全世界重視中、西藥併用之安全性。除了cyclosporine外，tacrolimus與rapamycin也屬於臨床上常用的強效免疫抑制劑，當免疫抑制劑之血中濃度過高時會增加感染機會；血中濃度不足時又會造成器官排斥。依據合作研究室的結果顯示，併服黃酮類化合物槲皮素或芸香苷均導致cyclosporine之血中濃度顯著降低。另外，許多研究指出槲皮素具有調節免疫系統之功能。因槲皮素大多以配糖體的型式存在中藥中，如芸香苷為槐花的主成分，而芸香苷於腸道中必須水解成槲皮素的型式方能吸收。本研究計畫擬以系統生物學方法，探討免疫系統、芸香苷、免疫抑制劑三者之交互作用後之藥動學及藥效學表現。第一年：擬建立平台評估單服免疫抑制劑(cyclosporin、tacrolimus或rapamycin)與併服芸香苷後，免疫抑制劑在各組織中的分佈，以及對免疫細胞功能之影響；第二年：以皮膚移植及發炎小鼠之動物模式探討芸香苷與免疫抑制劑交互作用後對於移植物存活的時間長短，以及對發炎現象之影響；第三年：探討免疫系統、芸香苷、免疫抑制劑三者交互作用中可能參與之分子及其調節機制。藉此計畫建立系統生物學試驗平台，應有助於提供中西藥併用之安全資訊。 Transplant patients should receive immunosuppressants everyday to prevent graft rejection. Due to the acute organ rejection caused by coadministration of St. John，s Wort with cyclosporin, herb-drug interaction attracts increasing attention worldwide. In addition to cyclosporin, tacrolimus and rapamycin are also widely used potent immunosuppressants. However, supratherapeutic blood level of immunosuppressants would increase the chance of infection; subtherapeutic blood level would cause organ rejection. According to the results of our collaborative laboratory, coadministration of quercetin markedly reduced the blood level of cyclosporin. Many studies reported that quercetin modulated the immune responses. Therefore, based on system biology method, we attempt to investigate the pharmacokinetic and pharmacodynamic interaction among rutin, immunosuppressants and immune system. In the first year, we plan to monitor the levels of cyclosporin, tacrolimus and rapamycin in various tissues and the functions of the immune cells after coadministration of rutin and immunosuppressants. In the second year, skin transplant and inflammatory animal models will be used to investigate the effects of coadministration of rutin and immunosuppressants on the survival time of graft and severity of inflammation. In the third year, the molecules involved in the interactions among immune system after coadministration of rutin and immunosuppressants will be explored. In addition, hopefully the possible mechanism will be elucidated. Through this study, more information about the pharmacokinetic and pharmacodynamic interactions between rutin and immunosuppressants will be provided.330202 bytesapplication/pdf系統生物學; 免疫抑制劑; 黃酮類; 芸香苷; 藥動學; 藥效學System biology; Immunosuppressants; Flavonoid; Rutin; Pharmacokinetics; Pharmacodynamicsreport