Title

丹參萃取物-酚酸B鎂鹽對於6-Hydroxydopamine引發細胞死亡之保護效果

Translated Titles

Protective Effect of Magnesium Lithospermate B Prevents 6-Hydroxydopamine-induced SH-SY5Y Cell Death

DOI

10.6845/NCHU.2009.00183

Authors

柯舒涵

Key Words

酚酸B鎂鹽 ; 細胞死亡 ; 細胞週期 ; Magnesium lithospermate B(MLB) ; 6-hydroxydopamine ; Cell death ; Cell cycle

PublicationName

中興大學生命科學系所學位論文

Volume or Term/Year and Month of Publication

2009年

Academic Degree Category

碩士

Advisor

范瑞珍

Content Language

繁體中文

Chinese Abstract

丹參在中醫用來治療心血管疾病、肝病以及抗發炎已經行之有年,其中某些組成份更被發現具有抗氧化和神經保護的功能。酚酸B鎂鹽(magnesium lithospermate B, MLB)為丹參的水溶性萃取物,近來研究證實對於心血管疾病具有療效。部分研究指出酚酸B鎂鹽能夠有效降低因缺血所造成的器官損傷,藉由抑制鈉鉀幫浦,進而達到神經保護的效果。由於其對神經保護機制仍不清楚,本研究首先選擇人類神經細胞瘤(SH-SY5Y cells)作為實驗之細胞模式,並進一步以6-hydroxydopamine(6-OHDA)進行傷害,隨後觀察酚酸B鎂鹽加入後對細胞造成的作用及深入探討其做作用機制。在細胞存活率的結果顯示,SH-SY5Y細胞在6-OHDA處理後加入酚酸B鎂鹽2小時,會顯著性的提高其細胞存活率。此外,利用螢光染色、流式細胞儀以及西方點墨法檢測,其結果顯示酚酸B鎂鹽並不會造成細胞內ROS含量上升以及細胞核濃縮的情形;此外,酚酸B鎂鹽能有效降低6-OHDA誘導的鈣離子、Caspase-3以及PARP增加,以及磷酸化之ERK下降的情形。同時,本實驗於細胞週期分析結果顯示,6-OHDA誘導24小時之後,G1期SH-SY5Y細胞數目明顯增加,明顯呈現G1期阻滯的現象;隨後加入酚酸B鎂鹽2小時後,會減低G1期停滯的現象,使得細胞週期在進入S期,同時磷酸化之ERK也因為加入酚酸B鎂鹽有顯著上升的趨勢。因此我們推論酚酸B鎂鹽能顯著的對抗6-OHDA誘導的SH-SY5Y細胞凋亡和細胞週期阻滯於G1期,該作用可能與鈣離子的降低,Caspase-3減少,以及磷酸化ERK的表現有關。

English Abstract

Danshen is one of the most important ancient Chinese medicinal herbs. It is widely used to treat heart and brain diseases. Magnesium Lithospermate B (MLB), a hydrophilic danshen extract, has been successfully used in ischemic stroke and cardiovascular diseases. However, the cellular and molecular mechanisms underlying its therapeutic effect remained unclear. 6-hydroxydopamine (6-OHDA) is a widely used neurotoxin and was found to induce Parkinson’s disease like neurodegenerative features. Previous study showed that 6-OHDA induced cell death could be reduced by MLB. Nevertheless the exact mechanism is still under debate. Thus, in this study, we first established an oxidative stress model induced by 6-OHDA in human neuroblastoma SH-SY5Y cells. Then, we investigated whether MLB has therapeutic effect on 6-OHDA induced cell death. The result of cell cytotoxicity assay showed that treatment of MLB for at least 2 hours increased the survival rate of SH-SY5Y cell. Hoechst33258 staining indicated that nucleus condensation was much lower in MLB treated group than that in only 6-OHDA treated group. Application of Fluo-4 and H2DCF-DA showed that 6-OHDA-treated cells displayed a high level of intracellular calcium and ROS, respectively. However, the cells subsequently treated with MLB revealed a low level of calcium concentration but no a trace of ROS. We therefore suggest that MLB may prevent the apoptosis induced by 6-OHDA, and perhaps couple with up regulation of phospho-ERK and down regulation of caspase3 and PARP. Our results therefore imply that MLB may be able to modulate the level of intracellular calcium and phospho-ERK to prevent 6-OHDA induced cell death.

Topic Category 生命科學院 > 生命科學系所
生物農學 > 生物科學
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