2016-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/704151摘要：紅景天在我國是歷史久遠的中藥，含salidroside、tyrosol 等成分。Salidroside，有抗發炎和抗氧化的作用。Salidroside 可恢復mitochondria 作用；另一成分 tyrosol，也具有抗氧化能力。但對於急性發炎反應的治療效果，所知甚少。敗血症，嚴重型急性胰臟炎，急性出血性膀胱炎是常見發炎急症，我們將探討紅景天和salidroside、tyrosol 等活性化合物，在上述急症治療中的角色。本研究分為三部分：(一)敗血症,利用巨噬細胞培養和動物兩種實驗模式，利用cecal ligation and puncture(CLP)或腹腔注射LPS 誘發小鼠敗血症，予紅景天和活性化合物治療，了解癒後是否改善並探討機轉。假說是紅景天和活性化合物藉由活化SIRT1 抑制HMGB1 的分泌，改善敗血症小鼠癒後；SIRT1 抑制ER stress 改善敗血症癒後。(二)急性嚴重型胰臟炎，用acinar 細胞培養和小鼠實驗，予紅景天和活性化合物治療，觀察癒後是否改善並探討機轉，包括對粒線體功能，SIRT1、HMGB1 分泌的影響，討論抗氧化作用。(三)Cyclophosphamide 和代謝物acrolein 誘發出血性膀胱炎。利用紅景天和活性化合物治療出血性膀胱炎，以及對不正常收縮是否有助益。並探討抗氧化作用和其他相關機制。本研究完成後對於紅景天和活性化合物對於急性發炎反應治療效果必定有所了解，相信除了metformin 此可以增加粒線體的能量合成，但具有乳酸血症副作用的藥物外，應該可以找出一個更合適更安全的藥物。<br> Abstract: Rhodiola rosea, which grows at high altitude zone and has been used as a roborant for a longtime. Salidroside[2-(4-hydroxyphenyl) ethyl beta-D-glucopyranoside]、and tyrosol are the majorbioactive constituents of Rhodiola rosea. Salidroside the major ingredient in Rhodiola rosea, hasvarious pharmoacological properties, including antidiabetic, hepatoprotective, and antioxidativeeffects. However, there have been few studies on the effect of Rhodiola rosea and its extracts onacute inflammatory diseases such as sepsis, acute severe pancreatitis, and hemorrhagic cystitis.There are three part in our study. First of all, we will examine the effects of Rhodiola rosea andits extracted compounds on LPS-stimulated inflammatory responses in macrophages and thepotential role of SIRT1 signaling in this process. We also evaluate its in vivo anti-inflammatoryeffect. We will investigate whether these products can ameliorate acute lung injury and mortality inmurine sepsis models. Mice will be intraperitoneally administered either vehicle or these productsafter sepsis by cecal ligation and puncture or LPS intraperitoneal injection. The effects of Rhodiolarosea and its extracted compounds on early inflammatory stage , late inflammatory stage, SIRT1,mitochondrial bioenergetics, glucose metabolism, lipid peroxidation and ER stress will beevaluated.Secondly, we will test the hypothesis that Rhodiola rosea and its extracted compoundsattenuate severe acute pancreas injury and associated acute lung injury in a murine model of severeacute pancreatitis via the amelioration on early and late phases of inflammation. We also aim toexamine the delicate mechanism of Rhodiola rosea and its extracted compounds on SIRT1, ERstress, CHOP expression in cerulein-stimulated acinar cells.Thirdly, we will establish a hemorrhagic cystitis model by the intraperitoneal injection ofcyclophosphamide or intravesical instillation of its metabolite acrolein. The contractions of isolatedrat detrusor strips evoked by field stimulations (EFS) or by exogenous agonist and proteinexpression in the bladder were observed in the short (1h) and long (24 h) term. We will test thehypothesis of the possible improvement of the detrusor dysfunction by Rhodiola rosea and itsextracted compounds and discuss the possible mechanism. In addition, we will investigate thethorough mechanism of Rhodiola rosea and its extracted compounds in cyclophosphamide and itsmetabolite stimulated bladder urothelial cells.Taken together, we believe a fuller understanding of the effects and the molecular mechanism ofRhodiola rosea and its extracted compounds will be clearer in various acute inflammatory diseases.Metformin, an anti-diabetic agent, protects cells or tissues from acute oxidative stress-relatedmitochondrial injury and cell death. However, metformin-associated lactic acidosis is a rare butlife-threatening complicaiton. We believe we will find more reliable, and more effective traditionalherbal medication than metformin after this study.