探討維生素D3在運動衰竭與失血性休克動物模式下抗氧化及抗發炎作用

Abstract

維生素D3是人體所必需之營養素，除了傳統調節體內鈣質平衡的重要功能外，研究也已證實維生素D3同時具有許多效用，例如抗發炎、抗氧化等等生物活性。本研究目的為探討維生素D3在身體處於發炎反應與氧化壓力相關疾病的狀態下，是否對於損傷有所改善，以及了解其改善之機制為何。因此，本研究使用兩種分別與發炎反應和氧化壓力相關，卻又缺乏維生素D3應用相關探討之疾病模式作為實驗對象，此兩種疾病分別是衰竭性運動與失血性休克。衰竭性運動部分，第一階段動物實驗評估過證實維生素D3的確可以改善實驗動物之器官損傷。因此，此部分第二階段便利用組織切片以及免疫組織化學染色深入了解其改善原因，發現損傷較高之區域均有較高之氧化壓力反應，而給予維生素D之後氧化壓力顯著減少，故推斷維生素D可以藉由改善氧化壓力而減少衰竭性運動所造成之損傷；失血性休克部分，第一階段實驗同樣利用動物模式驗證維生素D在失血性休克中扮演的角色，發現其的確具有改善損傷之生物活性。於是在第二階段實驗中，利用細胞實驗進行探討，發現其改善機制並非直接增加受損組織細胞存活率，而是透過對免疫細胞中單核球之調控，間接減少損傷。在利用RT-PCR進行基因表現之分析後，確定維生素D可調控PPAR相關路徑，減少發炎反應前驅物質產生，進而降低發炎反應。因此，總和以上實驗數據，並考量到維生素D低毒性、無嚴重副作用的特點，本研究認為維生素D不失為發炎反應或是氧化壓力相關疾病輔助治療的一種好選擇。

Vitamin D3 is a kind of nutrition that well-known necessary for regulate calcium concentration in human blood circulation. Except the well-known function, Vitamin D had been proved that also has anti-inflammation and anti-oxidative stress bioactivity. In this study, we try to understand if Vitamin D3 can actually decrease the inflammation and oxidative stress related damage, and its mechanism. Therefore, we use hemorrhagic shock and exhaustive exercise animal models to mimic inflammation and oxidative stress related damage, and discuss the rescue effect of Vitamin D3 in this research. In the exhaustive exercise animal model, we confirm Vitamin D3 did relief the damage. Furthermore, results of IHC stain shows that Vitamin D3 reduced oxidative stress in damaged tissue. In the hemorrhagic shock animal model, we also found that Vitamin D3 can reduce tissue damage, but the mechanism is different: it regulated the inflammatory related cell monocyte, reduce the inflammation to the therapeutic effect. By RT-PCR results, we confirm that Vitamin D3 regulate monocyte bypass PPAR pathway. As a conclusion, considering very low side effects and significant rescue effects in these two models, we suggest that Vitamin D3 might be a good choose to adjunctive therapy with patients who have inflammation or oxidative stress related diseases.