- 學位論文
全氟碳化合物造成大鼠腎小管細胞凋亡和促進發炎反應
Perfluorinated chemicals-mediated inflammation and apoptosis in rat renal tubular cells
摘要
全氟碳化合物 (Perfluorinated chemicals, PFCs) 為有機化合物，主要結構在碳鏈中的氫原子被氟所取代，在生物體內具有持久、蓄積與毒性之特性，長期累積對人體健康具有潛在的危害。PFCs 包含全氟辛酸 (perfluorooctanoic acid, PFOA)、全氟壬酸 (perfluorononanoic acid, PFNA)、全氟辛烷磺酸 (perfluorooctanesulfonate, PFOS) 和全氟己烷磺酸 (perfluorohexylsulfonate, PFHxS)。研究指出在美國有百分之九十八的人可被測出血液中含有PFCs 且發現與慢性腎臟疾病和尿酸血症有關，而PFCs 主要累積在肝腎兩處。本篇研究是針對PFCs對腎小管細胞造成細胞凋亡和發炎反應的分子機轉。結果證明PFCs導致腎小管細胞凋亡並增加促凋亡蛋白caspase-3 與Bcl-xs 之蛋白量。在促發炎研究中證明PFCs 促進hypo-pNFAT3、PPARα 以及促發炎蛋白NF-κB p65 轉移到細胞核，並使細胞間黏附分子-1 (intercellular adhesion molecule-1, ICAM-1) 與單核細胞趨化蛋白-1 (monocyte chemotactic protein-1, MCP-1) 基因表現增加，同時抗氧化作用之麩胱甘肽過氧化酵素基因 (glutathione peroxidase-1, GPx-1) 表現量減少。當我們給予抗氧化劑之N-乙醯基半胱氨酸 (N-acetylcysteine, NAC)作用下，PFCs 所造成ICAM-1 與MCP-1 之基因表現量減少。因此我們證明PFCs 導致腎小管細胞走向細胞凋亡和促進細胞發炎反應。
並列摘要
Perfluorinated chemicals (PFCs) are organofluorine compounds with all hydrogens replaced by fluorine on a carbon chain. PFCs are widespread environmentally, persistent and bioaccumulative chemicals with multiple toxicities reported, and are potentially harmful to human health. PFCs, including perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexylsulfonate (PFHxS) and perfluorononanoic acid (PFNA), are manmade chemicals that have been detected in the blood of more than 98% of the US population. Liver and kidney are two primary tissues of distribution of PFCs in Mammal. Previous study showed that PFCs elevated levels of PFCs in blood are associated with hyperuricemia and chronic kidney disease (CKD). In the study, we examine the effect of PFOS and PFHxS on renal tubular cells apoptosis and inflammation. We demonstrate that PFCs-mediated apoptosis through increased activation of caspase-3 and Bcl-xs protein levels. PFOS and PFHxS enhanced nuclear translocation of NF-κB p65, hypo-pNFAT3 and PPARα. Furthermore, the addition of N-acetylcysteine (NAC), an antioxidant, had effectively reversed cell apoptosis induced by PFOS and PFHxS. NAC prevented RTC from PFCs-mediated gene expression of proinflammatory chemokine such us intercellular adhesion molecule-1(ICAM-1) and monocyte chemotactic protein-1 (MCP-1). Meanwhile, mRNA level of glutathione peroxidase-1 (GPx-1), an antioxidant is reduced by PFOS and PFHxS challenge. Taken together, the results of our study demonstrate that PFCs cause cell apoptosis and inflammation in rat renal tubular cells.