国际权威的医学学术期刊American Journal of Respiratory and Critical Care Medicine近日刊登了一篇关于慢阻肺持续存在的细胞死亡文章《The Saga of Necroptosis in Chronic Obstructive Pulmonary Disease Continues》。

        文章概要如下

        慢性阻塞性肺疾病(COPD)是一种常见的呼吸系统疾病，慢性炎症导致不可逆的气道重塑和气道结构破坏，导致慢性支气管炎和肺气肿。据预测，到2030年，慢性阻塞性肺病将成为全球第三大死因，而目前仍缺乏有效治疗方法。

        吸烟(CS)暴露是COPD发展的主要危险因素，随后的氧化应激、炎症和生长因子信号的失衡引起肺内上皮细胞、内皮细胞和免疫细胞室的失调和(或)死亡。其相关治病途径及方式目前仍有待研究，目前慢阻肺的治疗仍然是以改善症状为主，气道慢性存在的炎症持续存在。

        人体在受到烟雾刺激，细胞应激和/或损伤后，调控细胞死亡(RCD)途径是基因编码的程序，可以维持组织内环境稳定，同时RCD途径也可以代表组织损伤的发病机制中的异常反应，导致人类疾病的有害后果。

        细胞凋亡是RCD的典型形式，其中半胱氨酸蛋白酶的激活与染色质缩合、细胞收缩、DNA片段和最终线粒体功能障碍有关，残存的细胞片段被包含在被吞噬的凋亡小体中，使得这种形式的RCD是非炎症性的。

        细胞坏死依赖于坏死小体形成的信息，坏死小体是通过激活RIPK1和RIPK3(受体相互作用的丝氨酸/苏氨酸蛋白激酶1和3)以及随后的MLKL(混合谱系激酶结构域样蛋白)磷酸化形成的，MLKL是细胞死亡的诱导物，与凋亡相反，这一途径是通过释放死亡细胞释放损伤相关分子模式的强诱导剂。类似的途径还有很多。

        细胞死亡失调是人类COPD肺组织的一个已知特征，与肺气肿表型相关。肺泡内皮细胞和上皮细胞都经历了细胞死亡，但是否有一种细胞类型导致了这种疾病尚不清楚。很多途径也有待进一步研究。这些坏死途径有可能作为COPD治疗的潜在靶点，坏死性抑制物是可用的，它们作为COPD治疗的潜在效用是非常令人感兴趣的。

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