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阮雍順醫師 Coenzyme Q10 protect against ischemia/reperfusion induced biochemical and functional changes in rabbit urinary bladder 2008/5/28 下午 05:51:53 0
原 文 題  目 Coenzyme Q10 protect against ischemia/reperfusion induced biochemical and functional changes in rabbit urinary bladder
作  者 Yung-Shun Juan, Tasmina Hydery, Anita Mannikarottu, Barry Kogan, Catherine Schuler, Robert E. Leggett, Wei-Yu Lin, Chun-Hsiung Huang, Robert M. Levin
出  處 Molecular and cellular Biochemistry
出版日期 2007, December ; Paper in press
評 論 有越來越多的證據證明反覆的膀胱壁缺氧後再灌流,是膀胱出口組塞、糖尿病以及動脈硬化等病變引起膀胱功能障礙的一個重要原因。在膀胱排空尿液時,膀胱壁增加的壓力會壓迫膀胱的血管造成短暫的缺氧;而在膀胱放縮收集尿液時,血流重新回流造成膀胱再灌流。如此反覆性的缺氧再灌流會增加游離基的傷害,而在膀胱有病理性的病變時,這種傷害更為明顯。
Coenzyme Q10是一種脂溶性的輔脢,他的作用主要是在細胞的粒線體內充當電子鏈的傳遞物,以增加粒線體製造能量的效率。他也是一種強力的抗氧化劑,並可以增加另一種抗氧化劑-維生素E的效果。在心臟方面的研究可以發現心肌缺氧時,細胞內輔脢Q10的量會減少,而投與輔脢Q10則可以增加心臟收縮的效率。目前在市面上也可以發現各式各樣加上輔脢Q10的皮膚保養品,號稱可以使皮膚青春永駐呢。筆者利用動物實驗模式將白兔膀胱動脈阻斷造成短暫缺氧(兩小時)之後,再將血管夾放開讓膀胱恢復兩星期;各實驗動物分別給予輔脢Q10或安慰劑,比較各組之間的差異。結果可以發現給予輔脢Q10大白兔的膀胱收縮力,檸檬酸合成酶(代表粒線體功能)以及蛋白質氮化以及氧化(代表游離基傷害程度)的現象都有明顯改善。這些結果顯示輔脢Q10確實可以減少膀胱缺氧後再灌流的傷害。
雖然在動物實驗上有相當好的結果,然而對於臨床上膀胱出口阻塞的膀胱功能障礙或是過動性膀胱等疾病,是否具有同樣的效果,仍需更進一步的臨床試驗。這種抗氧化劑的投予合併傳統手術與藥物的治療,也許可以讓我們臨床醫師在治療疾病時有新的思考方向。
abstract Purpose:Ischemia, reperfusion, and free radical generation have been recently implicated in the progressive bladder dysfunction. Coenzyme Q10 (CoQ10) is a pro-vitamin like substance that appears to be efficient for treatment of neurodegenerative disorders and ischemic heart disease. Our goal was to investigate the potential protective effect of CoQ10 in a rabbit model of in vivo bilateral ischemia and ischemia/reperfusion (I/R).
Material and Methods:Six groups of four male New Zealand White rabbits each were treated with CoQ10 (3 mg/kg body weight/day—dissolved in peanut oil) (groups 1–3) or vehicle (peanut oil) (groups 4–6). Groups 1 and 4 (ischemia-alone groups) had clamped bilateral vesical arteries for 2 h; in groups 2 and 5 (I/R groups), bilateral ischemia was similarly induced and the rabbits were allowed to recover for 2 weeks. Groups 3 and 6 were controls (shams) and were exposed to sham surgery. The effects on contractile responses to various stimulations and biochemical studies such as citrate synthase (CS), choline acetyltransferase (ChAT), superoxide dismutase (SOD), and catalase (CAT) were evaluated. The protein peroxidation indicator, carbonyl group, and nitrotyrosine contents were analyzed by Western blotting.
Results:Ischemia resulted in significant reductions in the contractile responses to all forms of stimulation in vehicle-fed rabbits, whereas there were no reductions in CoQ10-treated rabbits. Contractile responses were significantly reduced in vehicle-treated I/R groups, but significantly improved in CoQ10-treated rabbits. Protein carbonylation and nitration increased significantly in ischemia-alone and I/R bladders; CoQ10 treatment significantly attenuated protein carbonylation and nitration. CoQ10 up-regulated SOD and CAT activities in control animals; the few differences in CoQ10-treated animal in SOD and CAT after ischemia and in general increase CAT activities following I/R.
Conclusions:CoQ10 supplementation provides bladder protection against I/R injury. This protection effect improves mitochondrial function during I/R by repleting mitochondrial CoQ10 stores and potentiating their antioxidant properties.
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