炎症小体NLRP3在子痫前期中的研究进展

doi:10.12280/gjfckx.20221032

摘要/Abstract

摘要：

子痫前期（pre-eclampsia，PE）是一种以胎盘及全身系统性炎症为特征的妊娠并发症。PE归类于妊娠期高血压疾病，有进一步发展为子痫的可能，是影响母胎妊娠结局及预后的重要因素，严重影响母婴健康。PE的病理生理机制仍然在进一步的研究中，目前临床上对血压和蛋白尿的检查仍然是识别和诊断PE的重要方式，及时终止妊娠是目前治疗的重要措施。全身系统性的炎症反应是PE发病机制的关键。研究表明，炎症小体NOD样受体家族含pyrin结构域蛋白3（NOD-like receptor family pyrin domain-containing protein 3，NLRP3）是触发级联式炎症反应的“交通枢纽”，是促使炎症因子产生、引起PE炎症反应的“扳机”，NLRP3的激活或抑制与PE的发病及严重程度有关。因此，寻找NLRP3活性改变的原因对于了解PE发病机制及靶向治疗具有重要意义。

关键词: 先兆子痫, NLR家族, 热蛋白结构域包含蛋白3, 炎症, 妊娠, 胎盘

Abstract:

Pre-eclampsia(PE) is a pregnancy complication characterized by placental and systemic inflammation. It is classified as hypertensive disorder during pregnancy and may develop into eclampsia. It is an important factor affecting the outcome and prognosis of maternal and fetal pregnancy, and seriously affects the health of mother and infant. However, its related pathophysiological mechanism is still under further study, and currently clinical examination of blood pressure and proteinuria is still an important way to identify and diagnose PE, and timely termination of pregnancy is an important treatment measure. Systemic inflammation is the key to the pathogenesis of PE. Studies have shown that the inflammasome NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) is the "traffic hub" that triggers the cascade inflammatory response, and the "trigger" that promotes the production of inflammatory factors and causes the inflammatory response of PE. The activation or inhibition of NLRP3 is related to the onset and severity of PE. Therefore, it is of great significance to find the cause of the change of NLRP3 activity for understanding the pathogenesis and targeted therapy of PE.

Key words: Pre-eclampsia, NLR family, pyrin domain-containing 3 protein, Inflammation, Pregnancy, Placenta

李书明, 关红琼. 炎症小体NLRP3在子痫前期中的研究进展[J]. 国际妇产科学杂志, 2023, 50(3): 327-331.

LI Shu-ming, GUAN Hong-qiong. Research Progress of Inflammasome NLRP3 in Pre-Eclampsia[J]. Journal of International Obstetrics and Gynecology, 2023, 50(3): 327-331.

图/表 2

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激活物	受体	效应
内质网应激	TXNIP	激活炎症小体NLRP3，引起PE样症状^[11]
S100A9蛋白	NLRP3	激活炎症小体NLRP3和IL-1β，中性粒细胞积聚和可溶性内切酶含量增高^[8]
胆固醇晶体	-	激活炎症小体NLRP3、IL-1β表达增加、蜕膜产生炎症^[22]
LPS	激活氧化应激	促进NLRP3、caspase-1转换酶和IL-1β表达^[2,9,23]
尿酸钠	-	炎症小体NLRP3、NF-κB、IL-1β、IL-18和TNF-α含量增加，产生过度炎症反应^[21]
细胞外囊泡、血小板	ATP、嘌呤能信号	滋养层细胞中NLRP3激活，触发PE样症状^[25]

激活物	受体	效应
内质网应激	TXNIP	激活炎症小体NLRP3，引起PE样症状^[11]
S100A9蛋白	NLRP3	激活炎症小体NLRP3和IL-1β，中性粒细胞积聚和可溶性内切酶含量增高^[8]
胆固醇晶体	-	激活炎症小体NLRP3、IL-1β表达增加、蜕膜产生炎症^[22]
LPS	激活氧化应激	促进NLRP3、caspase-1转换酶和IL-1β表达^[2,9,23]
尿酸钠	-	炎症小体NLRP3、NF-κB、IL-1β、IL-18和TNF-α含量增加，产生过度炎症反应^[21]
细胞外囊泡、血小板	ATP、嘌呤能信号	滋养层细胞中NLRP3激活，触发PE样症状^[25]

抑制物	中间物质	效应
SIRT1	ROS	抑制滋养层细胞中炎症小体NLRP3的活化及IL-1β的表达^[2]
高浓度miR-520c-3p	NLRP3	抑制炎症小体NLRP3的激活，降低IL-18、IL-1β和TNF-α的表达水平^[4]
二甲双胍	TLR4/NF-κB/PFKFB3信号通路	抑制氧化应激和炎症小体NLRP3诱导的细胞焦亡^[17]
NLRP3特异性抑制剂MCC950	NLRP3	抑制炎症小体NLRP3、IL-1β及sEng的表达^[8,31]
水飞蓟宾	NF-κB信号通路	炎症小体NLRP3、IL-1β、IL-18和TNF-α含量降低，IL-10含量增加^[21]
TBK1	mTORC1	抑制LPS诱导的炎症小体NLRP3激活、胎盘炎症和IL-1的表达^[30]
高浓度miR-135	PCSK6	NLRP3、IL-1β和TNF-α表达水平降低，减弱细胞凋亡和炎症，增强细胞的集落形成能力、生存能力、侵袭和迁移能力^[31]
维生素D	-	抑制尿酸钠诱导的炎症小体NLRP3、caspase-1转换酶、IL-1β和IL-18的mRNA和蛋白表达^[32-33]

抑制物	中间物质	效应
SIRT1	ROS	抑制滋养层细胞中炎症小体NLRP3的活化及IL-1β的表达^[2]
高浓度miR-520c-3p	NLRP3	抑制炎症小体NLRP3的激活，降低IL-18、IL-1β和TNF-α的表达水平^[4]
二甲双胍	TLR4/NF-κB/PFKFB3信号通路	抑制氧化应激和炎症小体NLRP3诱导的细胞焦亡^[17]
NLRP3特异性抑制剂MCC950	NLRP3	抑制炎症小体NLRP3、IL-1β及sEng的表达^[8,31]
水飞蓟宾	NF-κB信号通路	炎症小体NLRP3、IL-1β、IL-18和TNF-α含量降低，IL-10含量增加^[21]
TBK1	mTORC1	抑制LPS诱导的炎症小体NLRP3激活、胎盘炎症和IL-1的表达^[30]
高浓度miR-135	PCSK6	NLRP3、IL-1β和TNF-α表达水平降低，减弱细胞凋亡和炎症，增强细胞的集落形成能力、生存能力、侵袭和迁移能力^[31]
维生素D	-	抑制尿酸钠诱导的炎症小体NLRP3、caspase-1转换酶、IL-1β和IL-18的mRNA和蛋白表达^[32-33]