编者按
(1)抗病毒;
(2)抗病毒DNA/RNA复制;
(3)免疫调控;
(4)支持细胞和全身系统。
图1
免疫营养调控——
常见的有益营养成分:
临床试验和综述
▲ 多发性创伤后患者的免疫营养:“在创伤后的恢复期内,即受伤后1-72小时,免疫炎症反应受到限制。临床医生唯一可用的策略是免疫营养,这应被视为改善危重和创伤患者免疫功能,和减少败血症和其他并发症的合理方法。”
维生素D3
(胆钙化固醇,而非麦角钙化醇):
▲ 每天常规剂量:4,000-10,000 IU;对于体弱患者的急性感染,采用常规维持剂量的同时,可以考虑一次性负荷剂量100,000-300,000IU。
图2 维生素D与免疫防护
维生素C(抗坏血酸):
维生素A:
▲ 下面列出了几项研究,这些文献记录了先后使用大剂量维生素A的情况。临床医生必须了解潜在的不良反应,必须适当地监测和选择患者,在这些临床试验中列出的持续时间内,一般不应使用高剂量。
♦ 维生素A适用于麻疹患者:“世界卫生组织建议,根据年龄,对所有被诊断患有麻疹的儿童,不论其居住国,都补充维生素A,具体方案如下:
♦ 大剂量维生素A的使用和安全性的文献:用大剂量维生素A辅助治疗I期:“视黄醇棕榈酸酯每天口服300,000 IU,12个月。结论:每日口服高剂量维生素A可有效减少与吸烟有关的新发原发肿瘤的数量,并可延长治愈的I期肺癌患者的无病间隔时间。”
♦ 高剂量维生素A的使用和安全性文献:高剂量维生素A的安全性。肺癌化学预防的随机试验:给予视黄醇棕榈酸酯每天300,000 IU,至少12个月,作者报告了他们在此类剂量安全性方面的经验。皮肤干燥和脱屑是最常见的症状,影响了所有治疗患者的60%左右。不到10%的患者出现了其他症状,例如消化不良、头痛、流鼻血和轻度脱发,并且这些症状会自行终止。只有4名患者(3%)因维生素A有关的症状而中断了治疗。”
♦ 高剂量维生素A的使用和安全性文献:高剂量维生素A使用期间的实验室评估:手术切除后肺癌患者的随机研究:
① 大剂量维生素A的不良反应包括血清γ-谷氨酰转移酶升高,其中69%的患者γ-谷氨酰转移酶异常升高,而对照组升高仅为39%(24个月时平均值149 vs 57 IU /L)。
② 血清甘油三酯升高浓度(在12个月时,接受治疗的患者中74%观察到甘油三酯升高到150 mg/dl以上,平均浓度为283 mg/dl;而对照组升高仅为43%。文章还提示:“根据经验,每天30万IU棕榈酸视黄酯可以作为一种预防剂量使用,且安全性最高可达2年。”
脂肪酸:
▲ 临床试验:柠檬味鳕鱼肝油和多种维生素矿物质补充剂,用于中耳炎二级预防:“8名儿童接受了1茶匙柠檬汁味鳕鱼肝油(含EPA和维生素A)和每天口服含硒儿童咀嚼多种维生素矿物质片剂。在这个OM季节中,研究对象在补充期间的抗生素使用天数比补充前减少了12.3%。”
▲ 临床试验:鳕鱼肝油和含硒的多种维生素矿物质补充剂对市区内拉丁裔儿童上呼吸道儿科就诊的影响:“补充剂组随时间的推移,上呼吸道感染的平均就诊次数在统计上有显著下降。使用这些营养补充剂随着时间的推移,上呼吸道感染的儿科就诊次数减少了。”
▲ 系统评价:重症患者的免疫营养:系统评价和文献分析:该系统评价比较了精氨酸、谷氨酰胺和/或鱼油各种组合的研究结果,得出结论:仅鱼油补充剂在死亡率和住院时间方面提供了一致的益处。“在接受鱼油(FO)和免疫调节饮食(IMD)的ICU患者中,死亡率,感染和住院时间显著降低(OR 0.42,95%CI 0.26-0.68;OR 0.45,95%CI 0.25-0.79和IMD -6.28天,分别为95%CI -9.92至-2.64)。”鱼油对这类患者的好处在于以下:
谷氨酰胺:
两餐之间每次3-9克,每天3次(TID IC):谷氨酰胺是条件性必需营养素,在创伤和感染期间,免疫细胞和肠上皮细胞需要的谷氨酰胺量会增加。可用的谷氨酰胺不足是导致免疫抑制和肠通透性增加的主要原因。临床医生应该意识到,补充谷氨酰胺是治疗革兰氏阴性脓毒症的理想配方。此外,还可以预期谷氨酰胺的不足会导致谷胱甘肽的缺乏和氧化应激的增加。谷胱甘肽是至关重要的抗氧化剂,具有调节细胞周期、DNA修复和炎症反应的多种功能,谷胱甘肽作为抗氧化剂,是由三个氨基酸,包括:半胱氨酸,甘氨酸和谷氨酰胺/谷氨酸内源合成的。这就解释了向有毒素暴露的患者提供半胱氨酸(通常以N-乙酰半胱氨酸的形式)和谷氨酰胺的获益 ,临床经常用于泰诺,即对乙酰氨基酚的过量。在临床实践中,两餐之间每天9-18克(通常在两餐之间使用氨基酸)是合理的。Garrel等人得出结论:对严重烧伤的患者给予谷氨酰胺可以高达26克/天,谷氨酰胺将感染风险降低了3倍,严重烧伤患者口服谷氨酰胺“可能是挽救生命的干预措施之一”。在临床试验中,以30g/d的剂量显示对镰状细胞性贫血患者的血流动力学有益处。目前最高谷氨酰胺剂量是Scheltinga等人的研究,癌症患者化疗后,静脉注射谷氨酰胺0.57g/kg/天;对于220磅的患者,这将使用大约57g/天的谷氨酰胺。
▲ 体外研究:谷氨酰胺增强术后患者中性粒细胞对细菌杀灭作用:并非所有研究都重复发现给于谷氨酰胺后嗜中性粒细胞抗菌作用增强的发现。然而,这些发现为谷氨酰胺对人体的抗感染和免疫支持作用提供了数据支持。同时,在无数次试验中已被证明,“这一发现表明,在体外试验中,随着血浆谷氨酰胺的增加(当谷氨酰胺的浓度从500 nmol/mL增加到1000 nmol/mL时),会增强嗜中性粒细胞对大肠杆菌的杀灭活性。总之,补充谷氨酰胺可以增强术后患者中性粒细胞的体外杀菌功能。
▲ 重症患者使用谷氨酰胺治疗可节省医院费用的临床试验和文献记录(尽管死亡率没有降低):给予谷氨酰胺肠内营养补充剂的重症患者的随机临床结局研究 :“给于谷氨酰胺治疗的患者在接受干预后重症监护病房(ICU)和住院患者的中位费用显著降低了23,000美元,对照患者为$30,900(P5=0.036)。对于接受谷氨酰胺治疗的患者,每个幸存者的费用降低了30%。”
▲ 随机临床试验:使用谷氨酰胺和益生菌进行早期肠内营养对脑损伤患者的益处:该脑损伤患者的临床试验表明,含有谷氨酰胺和益生菌的肠内配方降低了感染率、缩短了在重症监护室的停留时间;“与研究组(50%;P = 0.03)相比,对照组的感染率更高(100%);与对照组相比,每位患者的中位(范围)感染数明显更高(P <0.01)。”
▲ 在需要肠胃外营养的外科重症监护室(SICU)患者中补充丙氨酰-谷氨酰胺二肽的肠胃外营养的双盲,随机对照研究:肠外营养补充谷氨酰胺二肽可减少危重手术患者的医院感染:在SICU与标准医院两个不同的患者群体中,针对丙氨酰-谷氨酰胺补充的肠外营养(GLN-PN)进行肠外/静脉内营养(STD-PN):
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温故而知新专栏 | 病毒系列(5):支持抗病毒的免疫营养调控功能医学策略(下)
参考文献
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THE END
作者简介
李淼
心血管内科副主任
美国功能医学研究院(IFM)会员及认证医生
美国功能医学大学FMU认证医生
美国抗衰老协会(A4M)会员
感|谢|关|注
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