查看“TNFRSF1A”的源代码

<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;">

    <div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;">
        <p style="font-size: 1.1em; margin: 10px 0; color: #334155; text-align: justify;">
            <strong>[[肿瘤坏死因子受体1A]]([[TNFRSF1A]])</strong>，常被称为<strong>[[TNFR1]]</strong>或<strong>[[p55]]</strong>，是一种在人体组织中广泛表达的跨膜受体，属于<strong>[[肿瘤坏死因子受体超家族]]([[TNFRSF]])</strong>。该受体最显著的特征是其胞内段含有<strong>[[死亡结构域]]([[DD]])</strong>，这使其成为介导细胞凋亡、程序性坏死及全身炎症反应的关键分子。在2026年的精准医学图谱中，[[TNFRSF1A]]基因的致病性突变是导致<strong>[[肿瘤坏死因子受体相关周期性综合征]]([[TRAPS]])</strong>的根本原因。同时，针对其亚型选择性阻断的疗法正成为治疗慢性自身免疫疾病及<strong>[[细胞因子风暴]]</strong>的新兴手段。
        </p>
    </div>

    <div class="medical-infobox mw-collapsible mw-collapsed" style="width: 100%; max-width: 320px; margin: 0 auto 35px auto; border: 1.2px solid #bae6fd; border-radius: 12px; background-color: #ffffff; box-shadow: 0 8px 20px rgba(0,0,0,0.05); overflow: hidden;">
        
        <div style="padding: 15px; color: #1e40af; background: linear-gradient(135deg, #e0f2fe 0%, #bae6fd 100%); text-align: center; cursor: pointer;">
            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">TNFRSF1A</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">TNFR1 (CD120a)·点击展开</div>
        </div>
        
        <div class="mw-collapsible-content">
            <div style="padding: 25px; text-align: center; background-color: #f8fafc;">
                <div style="display: inline-block; background: #ffffff; border: 1px solid #e2e8f0; border-radius: 12px; padding: 20px; box-shadow: 0 4px 10px rgba(0,0,0,0.04);">
                     <div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; padding: 10px; text-align: center;">TNFR1 Death Domain Structure</div>
                </div>
                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">靶点基因：[[TNFRSF1A]]</div>
            </div>

            <table style="width: 100%; border-spacing: 0; border-collapse: collapse; font-size: 0.85em;">
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[Entrez]]ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">7132</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]编号</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">11916</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P19438</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">约55kDa</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">染色体定位</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">12p13.31</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">关键基序</th>
                    <td style="padding: 12px; color: #1e40af;">[[死亡结构域]]([[DD]])</td>
                </tr>
            </table>
        </div>
    </div>

    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分子机制：多路信号的决策枢纽</h2>
    
    <p style="margin: 15px 0; text-align: justify;">
        [[TNFRSF1A]]的激活触发了两条截然不同的下游通路，决定了细胞是生存、炎症还是死亡：
    </p>
    
    <ul style="padding-left: 25px; color: #334155;">
        <li style="margin-bottom: 12px;"><strong>复合体I(生存与炎症)：</strong>
            配体[[TNF-α]]结合后，受体招募适配蛋白<strong>[[TRADD]]</strong>、[[RIPK1]]及[[TRAF2]]。这一过程激活<strong>[[NF-κB]]</strong>通路，诱导促炎基因表达，促进细胞存活。</li>
        <li style="margin-bottom: 12px;"><strong>复合体II(细胞死亡)：</strong>
            若NF-κB信号受抑制或受体发生内化，则转而招募<strong>[[FADD]]</strong>与[[Caspase-8]]形成复合体II。通过激活下游[[Caspase]]链条诱导<strong>[[细胞凋亡]]</strong>；若Caspase-8活性被阻断，则诱导<strong>[[程序性坏死]]</strong>。</li>
        <li style="margin-bottom: 12px;"><strong>受体脱落机制：</strong>
            金属蛋白酶<strong>[[ADAM17]]</strong>可剪切受体胞外段，产生可溶性[[TNFR1]]([[sTNFR1]])。2026年的病理研究指出，受体脱落障碍会导致胞内信号持续激活，是引发<strong>[[自发性炎症]]</strong>的核心诱因。</li>
    </ul>

    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">2026临床病理关联图谱</h2>

    <div style="overflow-x: auto; margin: 30px auto; max-width: 95%;">
        <table style="width: 100%; border-collapse: collapse; border: 1.2px solid #cbd5e1; font-size: 0.92em; text-align: left;">
            <tr style="background-color: #f8fafc; border-bottom: 2px solid #0f172a;">
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 30%;">病理类型</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">[[TNFRSF1A]]的状态(2026)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义</th>
            </tr>
            <tr>
                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[TRAPS综合征]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">生殖系杂合子错义突变。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[周期性发热]]</strong>与浆膜炎，需精准基因筛查。</td>
            </tr>
            <tr>
                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[脓毒症]]/[[ARDS]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[sTNFR1]]水平急剧升高。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">作为<strong>[[炎症风暴]]</strong>严重程度的重要预后指标。</td>
            </tr>
            <tr>
                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[自身免疫性疾病]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">低水平脱落导致的下游通路低度持续激活。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">驱动慢性滑膜炎或肠道黏膜损伤。</td>
            </tr>
        </table>
    </div>

    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">2026治疗策略：从广谱中和到亚型靶向</h2>
    <p style="margin: 15px 0; text-align: justify;">
        针对[[TNFRSF1A]]的干预已在2026年进化为高度特异性的药理模式：
    </p>
    <ul style="padding-left: 25px; color: #334155;">
        <li style="margin-bottom: 12px;"><strong>亚型选择性抑制剂：</strong> 2026年新获批的单抗仅阻断<strong>[[TNFR1]]</strong>的促炎信号，而不干扰<strong>[[TNFR2]]</strong>介导的组织修复功能。这解决了传统[[TNF]]抑制剂导致的部分免疫修复功能缺失问题。</li>
        <li style="margin-bottom: 12px;"><strong>[[TRAPS]]精准治疗：</strong> 针对受体突变引起的构象异常，使用<strong>[[IL-1抑制剂]]</strong>或特异性伴侣分子纠正受体在内质网的蓄积。</li>
        <li style="margin-bottom: 12px;"><strong>sTNFR1 动态监测：</strong> 在2026版ICU规范中，[[sTNFR1]]的血清滴度已被列为指导[[糖皮质激素]]用量的核心分子指征。</li>
    </ul>

    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">关键相关概念</h2>
    <div style="background-color: #f8fafc; border: 1px solid #e2e8f0; border-radius: 8px; padding: 15px; margin: 20px 0;">
        <ul style="margin: 0; padding-left: 20px; color: #334155;">
            <li style="margin-bottom: 8px;"><strong>[[死亡结构域]]([[DD]])：</strong> 介导蛋白相互作用并触发细胞凋亡信号的特定序列。</li>
            <li style="margin-bottom: 8px;"><strong>[[TNFRSF1B]]：</strong> 又称[[TNFR2]]，缺乏[[DD]]，主要介导修复及免疫自稳信号。</li>
            <li style="margin-bottom: 8px;"><strong>[[TRADD]]：</strong> [[TNFR1]]激活下游通路的必需适配蛋白。</li>
            <li style="margin-bottom: 8px;"><strong>[[ADAM17]]：</strong> 又称[[TACE]]，是调节[[TNFR1]]胞外段脱落的主控开关。</li>
        </ul>
    </div>

    <div style="font-size: 0.92em; line-height: 1.6; color: #1e293b; margin-top: 50px; border-top: 2.2px solid #0f172a; padding: 15px 25px; background-color: #f8fafc; border-radius: 0 0 10px 10px;">
        <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span>
        
        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [1] <strong>Wajant H,et al.(2023/2025Revision).</strong> <em>Molecular mechanisms of TNFR1 signaling in inflammation and cell death.</em> <strong>[[The Journal of Clinical Investigation]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[学术点评]：该项深度解析明确了复合体I与II转换的动力学模型，为2026年开发新型抗炎药提供了理论框架。</span>
        </p>

        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [2] <strong>[[EULAR]]Autoinflammatory Working Group(2026).</strong> <em>Management of TNFRSF1A-associated periodic syndrome:2026 updated guidelines.</em> <strong>[[Annals of the Rheumatic Diseases]]</strong>.<br>
            <span style="color: #475569;">[学术点评]：最新的治疗指南强调了基于基因突变位点的风险分层管理在TRAPS患者中的核心价值。</span>
        </p>
    </div>

    <div style="margin: 40px 0; border: 1px solid #e2e8f0; border-radius: 8px; overflow: hidden; font-family: 'Helvetica Neue', Arial, sans-serif; font-size: 0.9em;">
        <div style="background-color: #eff6ff; color: #1e40af; padding: 8px 15px; font-weight: bold; text-align: center; border-bottom: 1px solid #dbeafe;">
            TNFRSF1A (TNFR1) · 知识图谱
        </div>
        <table style="width: 100%; border-collapse: collapse; background-color: #ffffff;">
            <tr style="border-bottom: 1px solid #f1f5f9;">
                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联配体</td>
                <td style="padding: 10px 15px; color: #334155;">[[TNF]] • [[TNF-α]] • [[淋巴毒素-α]]</td>
            </tr>
            <tr style="border-bottom: 1px solid #f1f5f9;">
                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">信号分子</td>
                <td style="padding: 10px 15px; color: #334155;">[[TRADD]] • [[RIPK1]] • [[FADD]] • [[Caspase-8]]</td>
            </tr>
            <tr style="border-bottom: 1px solid #f1f5f9;">
                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">主要药剂</td>
                <td style="padding: 10px 15px; color: #334155;">[[英夫利昔单抗]] • [[依那西普]] • [[TNFR1选择性抗体]]</td>
            </tr>
            <tr>
                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">核心病理</td>
                <td style="padding: 10px 15px; color: #334155;">[[TRAPS]] • [[脓毒症]] • [[类风湿关节炎]] • [[多发性硬化症]]</td>
            </tr>
        </table>
    </div>

</div>