一氧化碳解毒劑潛力: neuroglobin神經紅蛋白 !

一氧化碳中毒 可能有解藥 2016-12-08 14:00聯合晚報 編譯陳世欽／綜合報導 科學家正在實驗一氧化碳中毒的可能解藥。這種注射式的神經紅蛋白「拾荒者」，也許能在幾分鐘內，鎖住並移除血液中的一氧化碳。主持研究的匹茲堡大學血管生物學家葛雷德溫說：「我們已有氰中毒、蛇咬的解藥，卻沒有一氧化碳中毒的解藥。一氧化碳中毒是最普遍的中毒狀況。」研究團隊在大腦找到一種名為神經紅蛋白的蛋白質，加以基因改造後，使它可以選擇性鎖定並迅速困住一氧化碳，使一氧化碳無法附著於紅血球的血紅素。這種人工神經紅蛋白附著於一氧化碳的緊密度是一氧化碳附著於血紅素的500倍。葛拉德溫7日透過「科學轉化醫學」指出，在實驗過程中，人工神經紅蛋白曾經救回吸入致命濃度一氧化碳的老鼠。科學家必須更深入研究，才能進行人體實驗。一氧化碳是全球各地中毒致死的主因。在美國，每年有2萬多人因為火災以外的其他一氧化碳中毒而緊急送醫，400多人不治，兒童特別容易受到傷害。倖存者往往會出現長久的神經受損問題。燃燒燃料會產生一氧化碳。中毒的徵兆包括頭痛、暈眩、虛弱、噁心、嘔吐、胸痛或意識混亂。一氧化碳無色無味，會擠出紅血球所含的氧，導致腦部與其他組織缺氧。目前唯一的搶救方法是及時補充氧。血紅素攜帶紅血球的氧，而一氧化碳附著於血紅素的能力高於氧。如果人體吸入一氧化碳，它會取代血液中的氧。如能及時輸氧並排出一氧化碳，即可救命，然而沒有真正的解藥；人工神經紅蛋白可以直接鎖定一氧化碳，使輸氧急救法比較可能奏效。

An antidote for carbon monoxide poisoning? By Wudan YanDec. 7, 2016 , 2:00 PM On 26 January, Ling Wang and Qinzi Xu, two biomedical scientists at the University of Pittsburgh in Pennsylvania, placed a mouse under a chemical hood, anesthetized it, and hooked it up to monitors. Wang closed the hood and Xu turned on a switch to deliver 3% carbon monoxide (CO)—a concentration so high that it would kill most humans almost immediately—for 4.5 minutes. The mouse's blood pressure dropped precipitously and its heart rate turned irregular. Then, through an intravenous tube, they delivered a molecule their lab had developed. Moments later, the animal's blood pressure began to rise and it recovered. This was a first: There are no known antidotes for CO poisoning.  Given off by engines, heaters, and fireplaces, the tasteless, odorless gas sends more than 50,000 Americans to the emergency room—and kills approximately 500—every year. CO poisons in at least two ways. First, it binds tightly to the hemoglobin in blood and prevents it from delivering oxygen throughout the body. Second, it inhibits the process of respiration in mitochondria, cells' powerhouses. About the best physicians can now offer in cases of poisoning is a treatment developed more than 50 years ago: high-pressure oxygen."People have attempted some biochemical tricks to free carbon monoxide from hemoglobin, but they don't really work. That's why we literally have a therapy that's as old as oxygen," says Lance Becker, a physician at the Hofstra Northwell School of Medicine in Manhasset, New York. "So the idea of finding something that might work better, faster, and stronger is very appealing." That something, described in this week's issue of Science Translational Medicine, is neuroglobin—a protein typically found in the brain and retina that protects cells from injury by binding oxygen and nitric oxide—repurposed into a CO scavenger. The Pittsburgh research team, led by critical care physician Mark Gladwin, was originally studying its function when they noticed that isolated neuroglobin molecules almost always had CO, a natural byproduct of hemoglobin breakdown, bound to them. "I thought this was bad news at the time, because we needed to get the CO off the neuroglobin in an extra experimental step," Gladwin said. But when a colleague asked in 2012 whether there was any antidote for CO poisoning, he realized that his lab might already have an answer. In the mouse study, the group engineered a mutated version of neuroglobin that binds CO 500 times more tightly than it binds hemoglobin. The CO-laden molecules are excreted through the kidneys. When given within 5 minutes of a lethal dose of CO, the neuroglobin saved 87% of mice, the group reports. "This agent is phenomenal: It can rip carbon monoxide right off the hemoglobin," says Lindell Weaver, a doctor who treats patients with high-pressure oxygen at Intermountain Healthcare in Salt Lake City. Weaver notes, however, that CO poisoning also activates a series of immunological pathways that cause lingering damage to the nervous and cardiovascular systems. "The long-term effects of carbon monoxide are complicated, so just removing [it] might not be enough," he says. "But this agent could be life-saving if it's administered immediately." Gladwin's team now plans to further explore the efficacy and safety of the neuroglobin in rats, larger mammals, and, eventually, patients. One challenge will be making the neuroglobin scavenger in the amounts needed for use in the field and clinic. The U.S. Food and Drug Administration, Gladwin says, has already promised an expedited review of the treatment given that CO poisoning is a "serious unmet need."