利用海洋深層水預處理幹細胞可透過SIRT1抗氧化路徑修復由D-galactose所誘導老化大鼠的心臟功能
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2021
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心臟衰老是導致心血管疾病的關鍵因素之一，例如心功能下降和心肌梗塞。先前的研究證實，幹細胞具有自我更新和分化的能力，因此幹細胞在修復受損組織中起著重要的作用。幹細胞可以遷移到心臟，並通過周圍的微環境分化為新的心肌細胞，從而使衰老的心臟再生。實驗結果表明，海洋深層水（DSW）富含礦物質和有機營養素，並具有抗氧化和抗炎特性。目的： 本研究探討DSW的預處理是否可以增強幹細胞功能。如果可以的話，DSW預處理幹細胞對老化心臟再生的治療效果要比一般幹細胞治療的更有效。方法：間質幹細胞（MSCs）和DSW將用於研究DSW對幹細胞能力的增強作用。然後將進行衰老的動物模型以進一步闡明對DSW預處理的幹細胞的治療效果。結果： 細胞實驗證實DSW可通過激活IGF1R增強幹細胞功能。將8週齡的Wistar雄性大鼠用於老化動物模型，並將老鼠分為四組，包括Sham（6個月大的大鼠），Aging（以D-galactose誘導2個月 ），aging + Stem cell（以一般幹細胞治療）和aging + DSW-Stem cell（以DSW預處理後的幹細胞治療組）。先前的實驗結果表明，在老化組的心臟組織中可以觀察到cytochrome C, caspase 3等細胞凋亡蛋白的表現量有所上升；在本研究結果表明，在老化組p53老化蛋白質表現量上升； Sirt1，SOD等抗氧化蛋白表現量下調。相比之下，與Aging + Stem cell組（以一般幹細胞治療），Aging + DSW-Stem cell組（以DSW預處理後的幹細胞治療組）相比，心臟組織中的上述所有蛋白質表現均得到顯著改善。結論： 與普通幹細胞相比，DSW能夠增強幹細胞幹性，而DSW預處理的幹細胞在治療衰老引起的心力衰竭方面顯示出潛力。
Cardiac aging is one of the critical factors leading cardiovascular diseases, such as cardiac function decline and myocardial infarction. Previous researches indicated stem cells show self-renewal and differentiation abilities, so stem cells play an important role of repairing damaged tissues. Stem cells migrate to heart, and differentiate into new cardiomyocytes by surrounding microenvironment, leading to regenerate the aged heart. Previous studies indicated that deep sea water (DSW) is rich in minerals and organic nutrients as well as anti-oxidant and anti-inflammatory properties.Objective: This study was designed to investigate whether enhancement of capabilities for stem cells pretreated with DSW can be observed. If so, therapeutic effects on DSW pretreated stem cells for cardiac regeneration is better than stem cells without DSW pretreatment or not. Methods: Mesenchymal stem cells and DSW were used for investigating the enhancement of stem cell capability by DSW. Then aged animal model will be performed for further elucidate the therapeutic effect on DSW pretreatedstem cells. Result: The cell model confirmed that DSW can enhance stem cell capabilities through activation of IGF1R. Then 8 weeks-old Wistar male rats would be used for aged animal model and the animals were divided into four groups including Sham (rats with 6 months-old), Aging (Sham group with D-galactose administration for 2 months), Aging+SC (Aging group with stem cell transplantation) and Aging+DSW-SC (Aging group transplanted with DSW pretreated stem cells). One previous experimental results show that expression of apoptosis markers such as cytochrome C, caspase 3 increased and suppression of survival markers, such as p-Akt, IGF1R. In this study, experiential results indicated that downregulation of anti-oxidant markers including Sirt1, SOD can be observed in heart tissues of aging group. By contrast, all of above protein markers are significantly improved in heart tissues of Aging+DSW-SC group than Aging+SC group.Conclusion: Compared with ordinary stem cells, DSW is capable of increasing stem cell capabilities and DSW pretreated stem cells show better potential than stem cells without DSW preincubated in the treatment of heart failure induced by aging.
Cardiac aging is one of the critical factors leading cardiovascular diseases, such as cardiac function decline and myocardial infarction. Previous researches indicated stem cells show self-renewal and differentiation abilities, so stem cells play an important role of repairing damaged tissues. Stem cells migrate to heart, and differentiate into new cardiomyocytes by surrounding microenvironment, leading to regenerate the aged heart. Previous studies indicated that deep sea water (DSW) is rich in minerals and organic nutrients as well as anti-oxidant and anti-inflammatory properties.Objective: This study was designed to investigate whether enhancement of capabilities for stem cells pretreated with DSW can be observed. If so, therapeutic effects on DSW pretreated stem cells for cardiac regeneration is better than stem cells without DSW pretreatment or not. Methods: Mesenchymal stem cells and DSW were used for investigating the enhancement of stem cell capability by DSW. Then aged animal model will be performed for further elucidate the therapeutic effect on DSW pretreatedstem cells. Result: The cell model confirmed that DSW can enhance stem cell capabilities through activation of IGF1R. Then 8 weeks-old Wistar male rats would be used for aged animal model and the animals were divided into four groups including Sham (rats with 6 months-old), Aging (Sham group with D-galactose administration for 2 months), Aging+SC (Aging group with stem cell transplantation) and Aging+DSW-SC (Aging group transplanted with DSW pretreated stem cells). One previous experimental results show that expression of apoptosis markers such as cytochrome C, caspase 3 increased and suppression of survival markers, such as p-Akt, IGF1R. In this study, experiential results indicated that downregulation of anti-oxidant markers including Sirt1, SOD can be observed in heart tissues of aging group. By contrast, all of above protein markers are significantly improved in heart tissues of Aging+DSW-SC group than Aging+SC group.Conclusion: Compared with ordinary stem cells, DSW is capable of increasing stem cell capabilities and DSW pretreated stem cells show better potential than stem cells without DSW preincubated in the treatment of heart failure induced by aging.
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心肌衰老, 幹細胞, 海洋深層水, IGF1R, 粒線體動態, Myocardial aging, Stem cells, Deep sea water, Insulin-like Growth Factor 1 Receptor, Mitochondrial dynamics