Department of Pediatrics, the First Affiliated Hospital of Hainan Medical College, Haikou 570102, China.
J Physiol Pharmacol. 2024 Jun;75(3). doi: 10.26402/jpp.2024.3.10. Epub 2024 Jul 18.
Bronchopulmonary dysplasia (BPD) is a common serious complication of premature babies. No effective means control it. Hyperoxia damage is one of the important mechanisms of BPD. The reaserach confirmed pyroptosis existed in BPD. Dexmedetomidine is a new, high-specific α2 receptor agonist. Previous research foundation found that dexmedetomidine has a protective effect on BPD. To investigate how dexmedetomidine improves hyperoxic lung injury in neonatal mice by regulating pyroptosis. Neonatal rats were randomly divided into four groups: normal control group, hyperoxic injury group, air plus dexmedetomidine group, and hyperoxia plus dexmedetomidine group. After seven days the lungs of rats in each group were extracted, and the wet-to-dry weight ratio of the lung was measured. The lung injury in rats was observed using hematoxylin-eosin staining. Additionally, the expression and localization of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and gasdermin D (GSDMD) proteins were examined in the lungs of rats using immunofluorescence staining. The mRNA levels of NLRP3, ASC, caspase-1, and interleukin 18 (IL-18) in the lungs of rats were determined using real-time PCR. Moreover, the protein levels of NLRP3, ASC, caspase-1/cleaved caspase-1, interleukin 1beta (IL-1β), IL-18, and tunor necrosis factor alpha (TNF-α) were detected in lungs of rats using Western blot. The extent of mitochondrial damage in lung tissues of each group was observed by transmission electron microscopy. The lung tissue injury of the neonatal rats was significantly improved in the hyperoxia plus dexmedetomidine group compared to the hyperoxic injury group. Furthermore, the expressions of pyroptosis-related proteins such as NLRP3, ASC, cleaved-caspase-1, and GSDMD were significantly decreased, along with the expressions of inflammatory factors in lung tissues. By inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway, dexmedetomidine reduces the activation and release of inflammatory factors and provides a protective effect against hyperoxic lung injury in neonatal mice.
支气管肺发育不良（BPD）是早产儿常见的严重并发症。目前尚无有效的方法对其进行控制。过度氧暴露损伤是 BPD 的重要机制之一。研究证实，BPD 中存在细胞焦亡。右美托咪定是一种新型、高特异性的α2 受体激动剂。前期研究基础发现，右美托咪定对 BPD 具有保护作用。本研究旨在探讨右美托咪定通过调控细胞焦亡改善新生鼠高氧肺损伤的作用机制。将新生大鼠随机分为四组：正常对照组、高氧损伤组、空气加右美托咪定组和高氧加右美托咪定组。7 天后提取各组大鼠的肺组织，测量肺组织的湿干重比。苏木精-伊红染色观察大鼠肺损伤情况。免疫荧光染色检测大鼠肺组织核苷酸结合寡聚化结构域样受体热蛋白结构域相关蛋白 3（NLRP3）、凋亡相关斑点样蛋白（ASC）和 Gasdermin D（GSDMD）蛋白的表达和定位。实时 PCR 检测大鼠肺组织 NLRP3、ASC、半胱天冬酶 1 和白细胞介素 18（IL-18）mRNA 水平。Western blot 检测大鼠肺组织 NLRP3、ASC、半胱天冬酶 1/cleaved caspase-1、白细胞介素 1β（IL-1β）、IL-18 和肿瘤坏死因子 α（TNF-α）蛋白水平。透射电镜观察各组大鼠肺组织线粒体损伤程度。与高氧损伤组相比，高氧加右美托咪定组新生大鼠肺组织损伤明显改善。此外，NLRP3、ASC、cleaved-caspase-1 和 GSDMD 等焦亡相关蛋白的表达以及肺组织中炎症因子的表达均明显降低。右美托咪定通过抑制 NLRP3/caspase-1/GSDMD 细胞焦亡途径，减少炎症因子的激活和释放，对新生鼠高氧肺损伤起保护作用。
