细胞焦亡及其在角膜炎疾病中的作用机制研究进展

doi:10.11843/j.issn.0366-6964.2025.03.011

Abstract

Abstract:

Keratitis is an inflammation of the cornea caused by external pathogens or diseases, due to a reduction in the corneal defense ability. Pyroptosis is a programmed cell death related to inflammation. The pores formed on the cell membrane can allow the efflux of various inflammatory substances and mediate the inflammatory response. Studies have shown that keratitis is related to the occurrence of pyroptosis. Inhibiting the occurrence of pyroptosis can improve the clinical symptoms of the disease, which is a new direction for clinical treatment. This article reviews and summarizes the definition and morphological changes of pyroptosis, the mechanism of pyroptosis, the role of pyroptosis in keratitis, and the application of common pyroptosis inhibitors in ophthalmic diseases, to promote the research process of pyroptosis in keratitis.

Key words: pyroptosis, keratitis, prevention and control, inflammation

CLC Number:

S845

WANG Zhihao, GUO Long, WANG Peili, LI Jianji, WANG Heng. Progress of Pyroptosis and Its Mechanism of Action in the Keratitis Disease[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(3): 1089-1099.

Figures/Tables 1

Table 1

Characteristics of programmed cell death in different cells[13]"

项目 Item	焦亡 Pyroptosis	凋亡 Apoptosis	坏死 Necrosis	铁死亡 Ferroptosis	NETs的形成过程 NETosis	自噬 Autophagy
激活信号 Activate signal	DAMP和PAMP、dsDNA、病原体、LPS、炭疽致死毒素、微生物毒素和代谢产物、病毒RNA、ROS、细胞外ATP、溶酶体损伤、细胞膜对钾离子的渗透性等	DNA损伤、缺氧、病毒感染、毒素	缺血再灌注、物理或化学创伤、病毒或细菌感染	半胱氨酸或谷氨酰胺摄取减少，铁摄取增加，GPX4抑制	细菌成分、真菌β-葡聚糖、细胞因子	mTOR抑制剂，海藻糖，依托泊苷、十字孢碱、毒胡萝卜素处理
启动信号 Start signal	炎症小体的激活(例如，NLRP3、NLRC4、AIM2、pyrin等)/DR与TAK1结合/GzmA或GzmB激活/中性粒细胞弹性蛋白酶/组织蛋白酶G	死亡受体(TNF超家族)激活(外源性)/细胞内信号(内源性)	依赖于半胱天蛋白酶-8抑制的死亡受体激活(TNFR1、CD95、TRAIL-R1、TRAIL-R2、TLR3、TLR4、ZBP1)	xCT系统抑制，GSH耗竭	中性粒细胞表面受体的激活，如GPCR、TNF和Fc受体(中性粒细胞活化)	ULK复合体(由ATG101、ATG13、FIP200组成)和ATG9
调节信号 Adjust signal	NEK7	Caspase-8(外源性)/caspase-9 (内源性)	RIPK1-RIPK	GPX4抑制，FSP1抑制，CoQ₁₀减少，铁代谢相关蛋白，	PAD4、NE和MPO丝氨酸蛋白酶的联合作用	PtdIns3K复合物、ATG2Atg18/WIPI复合物、ATG12偶联系统、Atg8/微管相关蛋白1轻链3(LC3)偶联系统
执行蛋白 Execute protein	Caspase-1, caspase-4/5/11, caspase-3/8, gasdermin家族	Caspase-3/7	MLKL寡聚化，易位到质膜内叶	铁依赖性脂质过氧化	NETs失调, GSDMD	自噬体，自噬溶酶体
形态变化 Morphological changes	细胞外吐大泡	呈葡萄串状	细胞膨大、变形	-	-	产生空泡
质膜破裂 Rupture of plasma membrane	是	否(细胞膜完整)	是	是	是	否
细胞肿胀 Cell swelling	是	否(细胞皱缩)	是	否	是	否
核膜完整 Intact nuclear membrane	是	否	否	是	否	-
DNA断裂 DNA crack	是	是	是	否	否	-
染色质聚集 Chromatin aggregation	是	是	是	否	否	-
线粒体损伤 Mitochondrion damage	是(肿胀)	是	是(线粒体外膜破裂，线粒体嵴减少或消失，线粒体膜固缩)	是(膜密度、线粒体嵴减少或消失、线粒体外膜破裂)	是(肿胀)	是
细胞裂解死亡 Cell lysis and death	是	否	是	是	是	-
炎症 Inflammation	是	否	是	是	是	部分有

Table 1

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Progress of Pyroptosis and Its Mechanism of Action in the Keratitis Disease

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