對苯二胺對於膀胱造成損害情形之研究

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2013

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在現今社會,化學物質對苯二胺 (para-phenylenediamine; PPD) 因具有使毛髮氧化脫色之能力,因此常會被添加於一般民眾所使用之永久性染髮劑中。然而,PPD的使用長期以來被認為對於膀胱功能有所損害以及發生接觸性皮膚炎。為了釐清PPD對於膀胱造成的可能損害,我們使用腹腔注射的方式將PPD施打進入實驗動物體內為期一個月,以探討PPD對於膀胱功能的影響。藉由膀胱頂部插管以固定流速注入生理食鹽水的方式,進行膀胱壓力檢測;除此之外,為了更深入探討PPD所引起的傷害性,我們抽取了實驗動物的血液以及尿液樣本進行自由基數量的檢測,以及進行膀胱活體自由基數量檢測,此外也採得實驗動物的檢體進行病理切片觀察與使用西方墨點法進行計劃性細胞死亡之相關蛋白定量。而實驗結果顯示出,PPD會使膀胱收縮變得頻繁,也會造成血液與膀胱內部的氧化壓力增加。從病理切片發現到,PPD會使膀胱產生發炎。而西方墨點法結果也顯示:PPD會誘發兩種計畫性細胞死亡(細胞凋亡與細胞自我吞噬)。綜合上述結果可得知,PPD不僅會造成膀胱收縮功能的異常,也會促使血液中氧化壓力的上升以及膀胱組織的發炎,更會進一步使膀胱組織產生兩種不同路徑之計畫性細胞死亡。
Para-phenylenediamine (PPD) is a chemical substance that is widely used as a permanent hair dye. PPD via its toxic metabolites may induce some urinary bladder lesions and allergic contact dermatitis. To determine the occurrence and severity of urinary bladder dysfunction possibly caused by PPD, we used intraperitoneal injection of PPD for 4 weeks for induction of chronic bladder injury in the female Wistar rats. I measured bladder cystometrogram by saline infusion from the bladder dome in urethane anesthetized rats. I also measured the reactive oxygen species (ROS) in vitro and in vivo for oxidative stress and observed pathological changes in the formalin-fixed bladder sections. In addition, We explored the protein expression of apoptosis、autophagy and pyroptosis by western blot. The results showed that PPD treatment increased the frequency of micturition. PPD treatment alsoincreased the level of ROS in blood and urinary bladder (H2O2 related oxidative stress). We also found that PPD induced the number of leukocyte infiltration including neutrophils and mast cells in the damaged bladder sections. In addition, the result of western blot indicated that PPD treatment markedly induced autophagy, apoptosis and but not caspase-1 mediated pyroptosis. Our study results indicate that PPD induces oxidative stress and inflammatory leukocytosis in the urinary bladder, which subsequent causes bladder dysfunction, possibly involving autophagy and apoptosis menchanism.

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對苯二胺, 膀胱壓力值, 細胞凋亡, 自由基, para-phenylenedimine, bladder pressure, apoptosis, ROS

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