Abstract：
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.
摘要：
支气管肺发育不良（BPD）是早产儿常见的严重并发症。没有有效的手段控制它。高氧毁伤是BPD的重要机制之一。证实了BPD中存在焦亡。右美托咪定是一种新的，高特异性α2受体激动剂。先前的研究基础发现右美托咪定对BPD具有保护作用。探讨右美托咪定如何通过调节焦亡改善新生小鼠高氧肺损伤。将新生大鼠随机分为4组:正常对照组,高氧损伤组，空气加右美托咪定组，高氧加右美托咪定组。七天后抽取各组大鼠的肺部,并测量肺的湿干重量比。采用苏木精-伊红染色观察大鼠肺损伤情况。此外,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）的表达和定位，凋亡相关斑点样蛋白(ASC)，使用免疫荧光染色在大鼠的肺中检查了gasderminD（GSDMD）蛋白。NLRP3、ASC、使用实时PCR测定大鼠肺中的caspase-1和白介素18（IL-18）。此外，NLRP3，ASC，caspase-1/裂解的caspase-1，白细胞介素1β（IL-1β），使用Westernblot检测大鼠肺中的IL-18和膜坏死因子α（TNF-α）。透射电镜观察各组肺组织线粒体损伤程度。与高氧损伤组相比,高氧+右美托咪定组新生大鼠肺组织损伤明显改善。此外，焦亡相关蛋白如NLRP3、ASC、cleaved-caspase-1和GSDMD显著降低,肺组织中炎症因子的表达。通过抑制NLRP3/caspase-1/GSDMD途径，右美托咪定可减少新生小鼠高氧肺损伤时炎症因子的激活和释放，并具有保护作用。
