- 學位論文
丹參酮IIA磺酸鈉對Epirubicin引起之鼠心肌細胞毒性具有保護作用及其機制探討
Pretreatment of sodium tanshinone IIA sulfonate protects rat cardiomyocytes from epirubicin-induced cardiotoxicity
摘要
背景和研究動機: 自60年代開始使用Adriamycin做為抗癌藥物迄今，儘管化療藥物推成出新，但無論是單獨或合併使用其他化療藥物，這一類Anthracycline 藥物仍是化療的重要基石。其中Epirubicin 是當今最常用的一種化療藥物，但其獨特的心毒性影響了其使用範圍，甚至因這種嚴重的副作用影響了癌症病人的存活。Epirubicin 可能經由自由基損傷、鐵離子介入的氧化還原反應、鈣離子濃度變化及啟動一連串訊息傳遞，誘發細胞凋亡而導致心毒性的產生。迄今仍無確切的治療方法。丹參是傳統中醫使用於婦科及心血管疾病的重要藥物。由於現代研究發現其具有抗氧化壓力的作用，開啟丹蔘具心臟保護作用的研究。 實驗材料和方法: 本實驗藉由大鼠胚胎心肌H9c2細胞株，以細胞培養、MTT分析、流式細胞儀、及西方墨點法進行實驗。探討Epirubicin 導致心毒性的機制，併以丹參酮IIA磺酸鈉 Sodium Tanshinon IIA sulfate (STS)介入研究，分析其保護心肌細胞的作用及機制。 實驗結果: 研究證實丹參酮IIA磺酸鈉對 Epirubicin引起之心毒性確有保護作用。其機制除了減少自由基損傷，減少粒線體損傷，更重要的是調控以肌漿網為主的訊息傳遞：減少 calpain, caspase 12 以抑制細胞凋亡。除此之外，STS 也可活化AKT, 降調 JNK 和 NFκB 傳遞途徑達到調控細胞凋亡的目的。 結論:本研究的成果提示丹參酮IIA磺酸鈉對Epirubicin導致的心毒性具有保護作用並提出可能機制說明。期許未來可以應用於臨床治療癌症病人的輔助療法，以減少Anthracycline為基礎的化療的副作用。
並列摘要
Background and Motivation: Since the 1960s, Adriamycin started as an anti-cancer drug. So far, despite the push into a new chemotherapy drugs, but either alone or in combination with other chemotherapy drugs, Anthrocycline -based chemotherapy remains an important cornerstone. Which Epirubicin is the most commonly used chemotherapy drug, but its unique heart toxicity affects its use, or even serious side effects affecting the survival of cancer patients. Epirubicin may damage by free radicals, iron ions involved in the redox reaction, a calcium ion concentration and starting a series of signal transduction induced apoptosis,then, cardiac toxicity resulting generation. There is still no definitive treatment for far advanced cardiotoxicity . Danshen (丹蔘) is a important traditional Chinese medicine used in gynecological and cardiovascular diseases. Modern research has found that the anti-oxidative stress effect, open a cardioprotective effect Danshen series of studies. Materials and Methods: In this study, by H9C2 rat embryonic heart cells, cell culture, MTT analysis, flow cytometry, and Western blotting experiments. Explore Epirubicin lead to heart toxicity mechanisms and Danshen derivative Sodium Tanshinon IIA sulfate (STS) intervention study. Results: study confirmed the heart of STS on Epirubicin induced toxicity does have a protective effect. The mechanism in addition to reducing free radical damage, reducing mitochondrial damage, more importantly, within the endoplasmic reticulum-based regulation of signal transduction: reducing calpain, caspase 12 to inhibit apoptosis. In addition, STS can also be activated AKT, JNK and NFκB pathway down to achieve the purpose of regulation of apoptosis. Conclusion: The results of this study suggested Danshen has a protective effect to Epirubicin induced cardiotoxicity and possible mechanism for instructions. Expect future clinical treatment of cancer patients can be used in adjunctive therapy to reduce side effects of Epirubicin- based chemotherapy.
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