新冠肺炎治疗为么要用微生态制剂?
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;"><strong style="color: blue;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/ZgkvVf007wpsuBIRbRtwNYFYKR8Fv9mKnsRgBHo290RUfTuNiaRUlD2goHY4rM9R9iaEiaQ0X0FCGcLMPIEctlsicA/640?wx_fmt=jpeg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></strong></span></strong></p>
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<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;"><span style="color: black;">1、</span>支持应用微生态制剂的循证支持</span></strong></p><span style="color: black;">进入2月份底,新冠肺炎疫情防控进入关键时期。国家卫生健康委在其发布的《新型冠状病毒感染的肺炎诊疗<span style="color: black;">方法</span>》试行第五版、第六版和第七版中均指出:可<span style="color: black;">运用</span>肠道微生态调节剂,维持肠道微生态平衡,预防继发细菌感染。中国工程院院士、传<span style="color: black;">患病</span>诊治国家重点实验室<span style="color: black;">专家</span>李兰娟院士结合抗击H7N9的经验,提出治疗重症新冠肺炎<span style="color: black;">病人</span>要<span style="color: black;">保持</span>“四抗二平衡”,其中一平是“微生态平衡”。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_png/ZgkvVf007wpqZhP97VnKNe7hspksR9IYjBL2vAUJAslCHB1D225O9VebAicJzwukcZIH7e8oxZk9kI7lefCQmdg/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_gif/Ljib4So7yuWj7YIybz1Q0hhh0vuISibgtdyWFrhwI9oJTAA2Q0ytIf6JH6VXtM5BZEDeEnnzv19oHA734O2y0Ctw/640?wx_fmt=gif&tp=webp&wxfrom=5&wx_lazy=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;"><span style="color: black;">2、</span>微生态制剂抗击病毒的机制探讨</span></strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">1</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">调节肠道微生态平衡</span></strong></p><span style="color: black;">1) 酪酸梭菌:促进双歧杆菌等益生菌的生长,<span style="color: black;">控制</span>有害菌的生长和繁殖1。</span><span style="color: black;">2) 婴儿双歧杆菌:黏附性强,<span style="color: black;">形成</span>微生物屏障;产生抑菌物质<span style="color: black;">控制</span>外来致病菌对肠道的黏附、定植和入侵2,3。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">2</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">降低病毒感染</span></strong></p><span style="color: black;">1) 产丁酸菌:减少造血干细胞移植后的<span style="color: black;">呼气</span>道病毒感染4,<span style="color: black;">加强</span>甲流病毒感染的小鼠存活率,减少肺组织病理<span style="color: black;">损害</span>和血管渗漏5。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/ZgkvVf007wpqZhP97VnKNe7hspksR9IY2ia9dKQXnuPiaR7ibTpODH79VFcc4ClJSrHUm7TkYMudGu0M2F4NazlDw/640?wx_fmt=jpeg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">产丁酸菌减少造血干细胞移植后的<span style="color: black;">呼气</span>道病毒感染</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_png/ZgkvVf007wpqZhP97VnKNe7hspksR9IY7B6vjTpfJVUJkUYnzWNKWic7Zn5ObWtBtGLkWeODkDrg5j2kRnuiaCpg/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">丁酸可<span style="color: black;">加强</span>甲流病毒感染小鼠存活率,减少肺组织病理<span style="color: black;">损害</span>和血管渗漏</span></p><span style="color: black;">2) 乳酸菌:诱导肺部的Ⅰ型干扰素(IFN-Ⅰ)的产生,触发细胞<span style="color: black;">守护</span><span style="color: black;">功效</span>及抗病毒应答6,7。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">3</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">促进营养吸收</span></strong></p><span style="color: black;">1) 酪酸梭菌:主产丁酸(约80%),丁酸是肠上皮细胞维持正常<span style="color: black;">呼气</span>的<span style="color: black;">重点</span>能量<span style="color: black;">源自</span>(约80%)8。</span><span style="color: black;">2) 双歧杆菌、乳杆菌:主产乳酸和乙酸,调节肠道pH,可由产丁酸菌转化成丁酸后为肠上皮<span style="color: black;">供</span><span style="color: black;">能9</span><span style="color: black;">。</span></span><span style="color: black;">3) 乳酸杆菌、酪酸梭菌和双歧杆菌等:合成多种维生素,如叶酸、B族维生素、维生素K等15。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">4</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;"><span style="color: black;">加强</span>肠道屏障</span></strong></p><span style="color: black;">1) 酪酸梭菌和双歧杆菌:促进肠上皮紧密连接蛋白的表达,促进肠上皮细胞的增殖,维持肠道上皮的完整性,降低感染10,11。</span><span style="color: black;">2) 植物乳杆菌:靶向和修复受病毒破坏的肠道上皮细胞中的线粒体来修复肠道屏障15。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">5</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;"><span style="color: black;">加强</span>人体免疫</span></strong></p><span style="color: black;">1) 酪酸梭菌:诱导TGF-β分泌促进iTreg细胞增殖,调节免疫功能12。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">2) 婴儿双歧杆菌:<span style="color: black;">控制</span>NF-</span><span style="color: black;">κ</span><span style="color: black;">b的活化,<span style="color: black;">控制</span>IL-1b<span style="color: black;">导致</span>的肠黏膜<span style="color: black;">损害</span></span>13<span style="color: black;">。</span></p><span style="color: black;">3) 双歧杆菌:<span style="color: black;">控制</span>机体促炎因子的产生,<span style="color: black;">增多</span>机体抗炎细胞因子,<span style="color: black;">加强</span>自然杀伤细胞活力和吞噬能力,发挥免疫<span style="color: black;">功效</span>14。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_gif/Ljib4So7yuWj7YIybz1Q0hhh0vuISibgtdyWFrhwI9oJTAA2Q0ytIf6JH6VXtM5BZEDeEnnzv19oHA734O2y0Ctw/640?wx_fmt=gif&tp=webp&wxfrom=5&wx_lazy=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><strong style="color: blue;"><span style="color: black;">3、</span>新冠肺炎<span style="color: black;">病人</span><span style="color: black;">为何</span>要用</strong></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><strong style="color: blue;">微生态制剂?</strong></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">1</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">肠道与<span style="color: black;">呼气</span>道免疫密切<span style="color: black;">关联</span></span></strong></p><span style="color: black;">肠道是机体最大的免疫器官,消化道菌群<span style="color: black;">形成</span>和功能的改变<span style="color: black;">经过</span>黏膜免疫系统影响<span style="color: black;">呼气</span>道,而<span style="color: black;">呼气</span>道菌群<span style="color: black;">错乱</span><span style="color: black;">亦</span><span style="color: black;">经过</span>免疫调节影响消化道。这种肠道和肺部相互影响的<span style="color: black;">功效</span><span style="color: black;">叫作</span>为“肺-肠轴”,与中医理论“肺与大肠相表里”的机理一致15。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">2</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">新型冠状病毒感染的肺炎<span style="color: black;">病人</span>容易<span style="color: black;">出现</span>微生态<span style="color: black;">错乱</span></span></strong></p><span style="color: black;">2019新型冠状病毒感染肺部后<span style="color: black;">引起</span>肠道缺血缺氧,肠道微环境改变,<span style="color: black;">导致</span>肠道微生态<span style="color: black;">错乱</span>。肠道微生态<span style="color: black;">错乱</span>的<span style="color: black;">结果</span>是致病菌的<span style="color: black;">增加</span>。而致病菌可降解肠黏液,<span style="color: black;">增多</span>肠黏膜通透性,破坏肠屏障功能,<span style="color: black;">增多</span>感染<span style="color: black;">危害</span>,<span style="color: black;">导致</span>继发细菌感染。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">3</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">新型冠状病毒感染的肺炎<span style="color: black;">病人</span>临床表现容易<span style="color: black;">显现</span>腹泻的症状</span></strong></p><span style="color: black;">1) 与病毒感染性腹泻<span style="color: black;">相关</span>。2019新型冠状病毒是<span style="color: black;">经过</span>刺突(spike)蛋白与人体血管紧张素转化酶2(ACE2)结合,<span style="color: black;">从而</span>侵入人体细胞16。ACE2不仅在肺部组织表达,在肠道上皮<span style="color: black;">亦</span>有分布17。肠道中的ACE2蛋白能<span style="color: black;">经过</span>与氨基酸转运蛋白结合的方式,</span><span style="color: black;"><strong style="color: blue;">干扰人体对蛋白质等营养物质的吸收,<span style="color: black;">导致</span>消化道不适等症状18。</strong></span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_png/ZgkvVf007wpqZhP97VnKNe7hspksR9IYa6NQOYFic6icNGeEMu2ymXTsFbd87mB4PicQ8MnbtNPWHkCDTicINgzthQ/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p><span style="color: black;">2) 可能是治疗<span style="color: black;">药品</span><span style="color: black;">引起</span>的不良反应。抗病毒<span style="color: black;">药品</span>(如洛匹那韦/利托那韦)和抗菌<span style="color: black;">药品</span>(抗生素)的<span style="color: black;">运用</span>都容易<span style="color: black;">诱发</span>腹泻、恶心、呕吐等不良反应。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">4</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;"><span style="color: black;">身患</span><span style="color: black;">基本</span>病的中老年人微生态<span style="color: black;">错乱</span>早有伏笔</span></strong></p><span style="color: black;">随着年龄的<span style="color: black;">增多</span>,老年人肠道中有益细菌(如双歧杆菌、产丁酸菌、罗斯氏菌等)会减少,而耐氧菌和致病菌会<span style="color: black;">增多</span>,这些变化会<span style="color: black;">引起</span>菌群失调,肠黏膜免疫的功能降低,<span style="color: black;">从而</span><span style="color: black;">导致</span>多种<span style="color: black;">疾患</span>的<span style="color: black;">出现</span>,如心血管<span style="color: black;">疾患</span>、癌症、糖尿病和<span style="color: black;">呼气</span>系统<span style="color: black;">疾患</span><span style="color: black;">等</span>19,20<span style="color: black;">。</span></span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">5</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">出院新冠<span style="color: black;">病人</span>易留下消化不良的<span style="color: black;">副作用</span></span></strong></p><span style="color: black;">新冠肺炎<span style="color: black;">病人</span>被病毒感染后,免疫力降低。加上住院治疗<span style="color: black;">时期</span>接受了<span style="color: black;">海量</span>激素、抗病毒<span style="color: black;">药品</span>、抗菌<span style="color: black;">药品</span>的治疗,肠道有益菌<span style="color: black;">海量</span>减少,肠道微生态平衡被打破,肠道蠕动能力降低,易<span style="color: black;">显现</span>消化不良的<span style="color: black;">副作用</span>。即使出院后,<span style="color: black;">病人</span>仍需较<span style="color: black;">长期</span>恢复肠道菌群平衡。而<span style="color: black;">经过</span><span style="color: black;">弥补</span>微生态制剂<span style="color: black;">能够</span><span style="color: black;">帮助</span>机体营养吸收,促进恢复肠道微生态平衡。</span><span style="color: black;">益生菌是一种<span style="color: black;">平常</span>的微生态制剂,<span style="color: black;">日前</span>国家卫生健康委已<span style="color: black;">准许</span>的益生菌<span style="color: black;">药物</span>菌种类型较少,<span style="color: black;">重点</span><span style="color: black;">包括</span>:双歧杆菌属、酪酸梭菌、乳杆菌属等。在众多的肠道菌种中,<span style="color: black;">非常多</span>菌种之间存在互相促进、协同增效的<span style="color: black;">功效</span>,关于菌种之间的相互<span style="color: black;">功效</span><span style="color: black;">日前</span><span style="color: black;">科研</span>较为广泛,机制相对<span style="color: black;">知道</span>的是酪酸梭菌与其他菌株的<span style="color: black;">功效</span>。在临床应用过程中,</span><span style="color: black;"><strong style="color: blue;">酪酸梭菌和婴儿型双歧杆菌联合应用能起到协同增效的<strong style="color: blue;"><span style="color: black;">功效</span></strong></strong></span><span style="color: black;"><strong style="color: blue;"><strong style="color: blue;">21</strong></strong></span><span style="color: black;"><strong style="color: blue;">,<span style="color: black;">日前</span>已有成熟的制剂——酪酸梭菌二联活菌,在微生态制剂<span style="color: black;">选取</span>时可<span style="color: black;">做为</span>常规<span style="color: black;">举荐</span>。</strong></span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_png/ZgkvVf007wpqZhP97VnKNe7hspksR9IYLZe6YEZQCGIIToL0hrAmic45jSynglUtsqfpqibIXSJia1gtLEUCkmPKg/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">酪酸梭菌二联活菌减轻小鼠气道<span style="color: black;">炎</span><span style="color: black;">症22,23</span></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><strong style="color: blue;"><span style="color: black;">参考文献</span></strong></span></p>
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<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">Warnakulasuriya E.V. et al. Adherence of Probiotic Bacteria to Human Colonic Cells. Bioscience Microflora, 1998,17(2):105-113.</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">Huey-Chun Huang, et al. Antimelanogenic and antioxidative properties of Bifidobacterium bifidum. Archives of Dermatological Research, 2011,303(7):527-531.</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">Bastiaan W. Haak, et al. Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT. Blood: The Journal of the American Society of Hematology, 2018.</span></p>
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