遗传 ›› 2026, Vol. 48 ›› Issue (2): 177-200.doi: 10.16288/j.yczz.25-205
江山1,2,3(
), 雷宇航1,2,3(
), 廖天赐1,2,3, 钟易1,2,3, 甘麦邻1,2,3, 朱砺1,2,3, 沈林園1,2,3(
)
收稿日期:2025-08-04
修回日期:2025-09-09
出版日期:2026-02-20
发布日期:2025-11-04
通讯作者:
沈林園,博士,副教授,研究方向:猪的分子遗传与育种、猪生物育种技术研发与应用。E-mail: shenlinyuan@sicau.edu.cn作者简介:江山,本科生,专业方向:动物遗传育种与繁殖。E-mail: 202200429@stu.sicau.edu.cn基金资助:
Shan Jiang1,2,3(
), Yuhang Lei1,2,3(
), Tianci Liao1,2,3, Yi Zhong1,2,3, Mailin Gan1,2,3, Li Zhu1,2,3, Linyuan Shen1,2,3(
)
Received:2025-08-04
Revised:2025-09-09
Published:2026-02-20
Online:2025-11-04
Supported by:摘要:
红肉与白肉的健康效应争议长期存在,传统基于动物种属的二元分类体系难以匹配其营养异质性与疾病风险的复杂性。本文通过整合流行病学、分子机制及食品科学多维证据,系统重构了肉类健康评估框架。研究证实,传统红白肉定义因忽视种内差异及跨物种悖论,需转向基于部位、加工方式的精准分类;加工肉作为1 类致癌物与未加工红肉风险存在本质差异,后者适量摄入有助于平衡血红素铁/维生素B12的营养价值与相关健康风险;在致病机制上,红肉中血红素铁、Neu5Gc、TMAO及加工衍生的NOCs、HCAs/PAHs构成多重病理网络;而白肉因缺失核心毒性成分且富含ω-3 PUFA(EPA/DHA抗炎与神经保护),多数研究提示可能会降低心血管代谢风险,但高温加工可削弱其优势。基于此,国际指南形成“严控加工肉、限量未加工红肉、优选白肉”共识,并发展基因筛查、益生菌调控菌群-TMAO轴及低温烹饪等精准策略。未来需突破单细胞多组学解析器官特异性损伤、建立基因-菌群-营养素三元交互的个体化风险评估模型,并通过CRISPR育种靶向降低红肉毒性及AI优化膳食推荐系统,推动肉类消费向营养-健康-环境可持续性协同进化。
江山, 雷宇航, 廖天赐, 钟易, 甘麦邻, 朱砺, 沈林園. 红肉与白肉健康效应的多学科证据评估与机制整合[J]. 遗传, 2026, 48(2): 177-200.
Shan Jiang, Yuhang Lei, Tianci Liao, Yi Zhong, Mailin Gan, Li Zhu, Linyuan Shen. Multidimensional evidence assessment and mechanistic integration of the health effects of red and white meat[J]. Hereditas(Beijing), 2026, 48(2): 177-200.
表1
各类红白肉7种营养元素含量表"
| 类别 | 肉类种类 | 营养元素 | ||||||
|---|---|---|---|---|---|---|---|---|
| 铁 (mg) | 总脂肪 (g) | 饱和脂肪 (g) | 胆固醇(mg) | PUFAs (g) | EPA (g) | DHA (g) | ||
| 红肉 | 碎牛肉 | 2.88 | 4.46 | 2.210 | 88 | 0.281 | 0 | 0 |
| 侧腹牛排 | 1.80 | 9.31 | 3.840 | 81 | 0.390 | 0.003 | 0.001 | |
| 碎猪肉 | 1.05 | 7.15 | 1.950 | 78 | 0.776 | 0.003 | 0.004 | |
| 猪里脊肉 | 0.96 | 17.60 | 6.220 | 84 | 0.700 | 0 | 0 | |
| 白肉 | 火鸡腿肉 | 2.30 | 9.82 | 3.060 | 85 | 2.720 | 0 | 0.050 |
| 鸡腿肉 | 1.40 | 8.06 | 2.200 | 89 | 1.880 | 0.010 | 0.050 | |
| 蓝鳍金枪鱼 | 1.31 | 6.28 | 1.610 | 49 | 1.840 | 0.363 | 1.140 | |
| 鳕鱼 | 0.59 | 1.26 | 0.170 | 91 | 0.108 | 0.021 | 0.059 | |
| 虾 | 0.51 | 0.28 | 0.056 | 189 | 0.079 | 0.015 | 0.015 | |
| 鸡胸肉 | 0.43 | 3.61 | 1.190 | 99 | 0.660 | 0.010 | 0.020 | |
图1
血红素铁致病机制示意图 血红素铁通过芬顿反应和哈伯-韦斯反应催化活性氧(ROS)的生成。由此产生的ROS,特别是高活性的·OH,可通过两条主要途径诱导细胞损伤。首先,·OH可直接攻击DNA,导致8-oxoG的形成及随后的遗传毒性。这种DNA损伤还能通过调节OGG1和激活NF-κB来触发炎症级联反应,上调促炎细胞因子(TNF、IL-1β、CXCL1、CXCL2),从而促进肿瘤发生和癌症发展。其次,ROS可引发脂质过氧化,这是一个产生MDA和4-HNE等活性醛类的链式反应。这些副产物通过上调清道夫受体CD36,促进巨噬细胞对oxLDL的摄取,导致泡沫细胞的形成,最终促进动脉粥样硬化的病理进程。"
图2
晚期糖基化终产物(AGEs)致病机制 在高温烹饪红肉过程中产生的AGEs,在与其受体结合后,会启动多种致病信号级联反应。AGE-RAGE的相互作用通过激活NADPH氧化酶以及一个涉及RAC1和c-Src的DIAPH1依赖性途径,触发ROS的产生。这种氧化应激促进了动脉粥样硬化的发展。同时,AGE-RAGE轴激活多个下游通路,包括Ras-ERK1/2和PKC/MAPKs,这些通路共同作用于转录因子NF-κB。活化的NF-κB转移至细胞核,并上调多种促炎和粘附分子基因(如MCP-1、TNF-α、IL-6、VCAM-1、ICAM-1)的表达,从而促进炎症、癌症和肾脏疾病。此外,AGE-RAGE的结合可诱导内质网应激,抑制Slc2a4基因转录,导致GLUT4蛋白水平降低。由此引起的葡萄糖摄取障碍导致高血糖,并促进了糖尿病的发病。"
图3
多环芳烃(PAHs)和杂环胺类化合物(HCAs)致病机制 在经过细胞摄取后,PAHs和HCAs均可与AhR结合。活化的AhR-配体复合物转移到细胞核,与ARNT二聚化,并结合到靶基因启动子区域的XRE,显著上调细胞色素P450酶基因(CYP1A1、CYP1B1、CYP1A2)。这些酶分别将PAHs和HCAs代谢为高活性中间体和环外氨基羟基化代谢物。HCAs的代谢物可被NATs或SULTs进一步活化,形成亲电物质,这些物质易与DNA加合,导致DNA毒性和链断裂。除了直接的DNA损伤,这些活性代谢物还会诱导一系列表观遗传改变,包括组蛋白修饰失衡(如H3K9乙酰化、H3S10磷酸化、H3K36三甲基化的改变)、DNA甲基化异常(如p16INK4的高甲基化、LINE-1的低甲基化)和miRNA失调(如miR-22/494和miR-21的上调,miR-29b和let-7家族的下调)。这些表观遗传修饰共同导致基因组不稳定和基因表达异常,从而驱动癌变。此外,PAHs和HCAs通过AhR激活,通过调节NF-κB、MAPK和JAK/STAT等关键信号通路,触发免疫反应和炎症,加剧细胞损伤并促进疾病进展。"
图4
N-羟乙醇酰神经氨酸(Neu5Gc)致病机制示意图 膳食中的Neu5Gc是一种富含于红肉中的外源性唾液酸,通过多种信号通路发挥其促癌作用,尤其是在结直肠癌中。它通过结合HRAS和SRC等靶点直接激活PI3K-Akt通路,导致AKT2磷酸化以及细胞周期调节因子(CDK2、CCNA2)的上调,从而加速细胞周期进程并促进细胞增殖。此外,Neu5Gc增强Wnt3a配体-受体结合,激活Wnt通路,导致β-catenin积累和下游基因(AXIN2、MYC)表达增加,从而促进结直肠癌细胞增殖。除了致癌信号,Neu5Gc还通过IκB-α和P65磷酸化激活NF-κB通路,导致ROS产生增加和炎症,从而促进炎症性肠病。同时,Neu5Gc显著降低紧密连接蛋白(ZO-1、occludin、claudin-1、claudin-4)的表达,损害肠上皮屏障的完整性,促进病原体和细菌的易位。此外,Neu5Gc诱导肠道菌群失调,表现为有益菌(如Muribaculaceae、Lachnospiraceae、Prevotellaceae)减少,促炎菌(如Bacteroidetes、Firmicutes、Prevotellaceae_NK3B31_group、Clostridia UCG-014)增加,进一步激活NF-κB通路并加剧慢性炎症。"
图5
氧化三甲胺(TMAO)致病机制示意图 人体摄入红肉后,胆碱和左旋肉碱被肠道微生物代谢为TMA,TMA随后在肝脏中被FMOs氧化为TMAO。全身TMAO水平升高通过促进SERCA2a与自噬蛋白ATG5的相互作用,导致SERCA2a降解和随后的钙稳态失衡,从而导致心肌肥厚。在动脉粥样硬化中,TMAO通过MAPK/JNK通路,上调清道夫受体(特别是CD36),增强巨噬细胞泡沫细胞的形成,从而增加oxLDL的摄取。此外,TMAO扰乱胆汁酸代谢,改变血清胆汁酸谱(如DCA升高,TMCA降低),从而激活核受体FXR和SHP。这一级联反应抑制Cyp7a1的表达,减少胆汁酸合成并损害RCT,最终加速动脉粥样硬化斑块的进展。在胃肠道中,TMAO通过下调紧密连接蛋白(ZO-1、occludin),激活TLR4/MyD88/NF-κB炎症通路,并抑制Wnt/β-catenin通路,从而损害肠道屏障完整性,导致肠道通透性增加以及细菌/毒素易位。同时,TMAO通过诱导肝窦内皮细胞毛细血管化(CD31、vWF表达上调;eNOS表达下调),促进纤维化基因(α-SMA、TIMP1)表达,并将巨噬细胞极化偏向促炎M1表型(TNF-α、IL-1β、IL-6增加;IL-10减少),从而导致非酒精性脂肪肝(NAFLD),共同加剧肝脏炎症和纤维化。"
图6
N-亚硝基化合物(NOCs)致病机制示意图 NOCs由加工肉类中的亚硝酸盐经微生物生物转化形成,是一类重要的遗传毒性物质。NOCs主要包括N-NAs和N-亚硝酰胺两大类。N-NAs(如NDMA和NDEA),主要通过细胞色素P450酶(CYP2E1/CYP2A1)进行α-羟基化代谢活化,生成不稳定的α-羟基衍生物,这些衍生物自发分解为高活性的烷基重氮离子。相反,N-亚硝酰胺无需代谢活化即可直接烷基化DNA。这两种途径最终都导致DNA烷基化,形成DNA加合物(如O⁶-烷基鸟嘌呤、N⁷-烷基鸟嘌呤),增加错配,并损害DNA修复机制,最终导致DNA损伤。此外,NOCs的代谢活化会产生ROS,从而诱导氧化应激、进一步的DNA损伤、脂质过氧化和蛋白质加合物形成。这些细胞损伤通过激活促炎细胞因子(IL-1β、IL-6、TNF-α)和促进胰岛素抵抗,共同导致多种慢性疾病的发生,包括神经退行性疾病、癌症和2型糖尿病。"
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