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陆军军医大学大坪医院野战外科研究部第六研究室,重庆 400042
周 慈,Email:zhouci6524@tmmu.edu.cn,研究方向:爆炸武器伤的损伤特点及机制研究。
王建民,Email:jmwang@tmmu.edu.cn。
收稿:2025-10-09,
修回:2026-03-06,
录用:2026-03-20,
网络首发:2026-06-10,
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周慈, 邹杰, 邓蒙生, 等. 小鼠爆炸冲击伤后GNAS表达与肺泡上皮细胞骨架改变的相关性研究[J/OL]. 重庆医科大学学报, 2026,1-8.
Zhou Ci,Zou Jie,Deng Mengsheng,et al.Correlation between the expression of G-protein alpha subunit and cytoskeletal alterations in alveolar epithelial cells after blast-induced lung injury in mice[J].Journal of Chongqing Medical University,
周慈, 邹杰, 邓蒙生, 等. 小鼠爆炸冲击伤后GNAS表达与肺泡上皮细胞骨架改变的相关性研究[J/OL]. 重庆医科大学学报, 2026,1-8. DOI:
Zhou Ci,Zou Jie,Deng Mengsheng,et al.Correlation between the expression of G-protein alpha subunit and cytoskeletal alterations in alveolar epithelial cells after blast-induced lung injury in mice[J].Journal of Chongqing Medical University, DOI:10.13406/j.cnki.cyxb..
目的
2
探讨爆炸冲击伤不同损伤程度及不同时间G蛋白α亚基(G-protein alpha-subunit,GNAS)基因表达变化与肺泡上皮细胞骨架改变的时效、量效关系。
方法
2
8~10周龄的C57 BL/6雄性小鼠94只,随机分为2组,在距离爆炸物中心5.4 m和5.7 m处布放小鼠,致伤后随机取24只5.7 m冲击小鼠为冲击6、12、24、48 h组;随机取9只5.7 m冲击小鼠和9只5.4 m冲击小鼠,存活24 h后根据肺冲击伤病理严重度分级评分标准分为冲击轻度、中度和重度组,观察剩余小鼠48 h生存情况。采用苏木精-伊红染色观察各组小鼠肺组织损伤,采用酶联免疫吸附测定法检测各组小鼠肺组织中炎性因子含量,通过蛋白免疫印迹法检测各组肺组织中GNAS、细胞骨架与连接蛋白表达。
结果
2
光镜下各组冲击伤小鼠肺组织主要表现为肺泡结构破裂、融合,肺泡腔内出血、水肿,炎症细胞浸润。与对照组相比,不同损伤程度和损伤时间组的小鼠肺组织炎性因子白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α的含量
均明显升高(均
P
<
0.05)。与对照组相比,不同损伤程度和损伤时间组的GNAS蛋白表达均逐渐降低(均
P
<
0.05),同时不同损伤程度组细胞骨架蛋白(β-肌动蛋白、β-微管蛋白)、细胞连接蛋白(上皮-钙黏蛋白、闭锁小带蛋白-1)及黏着斑激酶也呈逐渐降低趋势(均
P
<
0.05);不同损伤时间组β-肌动蛋白、β-微管蛋白、闭锁小带蛋白-1及黏着斑激酶于6 h略有升高,随后逐渐降低(均
P
<
0.05),上皮-钙黏蛋白则随时间逐渐降低(
P
<
0.05)。
结论
2
小鼠肺冲击伤后引发强烈的炎症风暴,导致GNAS抑制和肺泡上皮细胞骨架-连接复合体的结构性破坏,且两者之间可能存在正相关性。
Objective
2
To investigate the time-effect and dose-effect relationships between the change in the expression of G-protein alpha subunit(GNAS) and cytoskeletal alterations in alveolar epithelial cells after blast-induced lung injury with different severities and durations.
Methods
2
A total of 94 male C57BL/6 mice,aged 8-10 weeks,were randomly divided into two groups and were placed at 5.4 m and 5.7 m from the blast epicenter,respectively. After injury induction,24 mice were randomly selected from the 5.7 m group and were divided into 6-hour,12-hour,24-hour,and 48-hour post-injury subgroups. Another 9 mice from the 5.7 m group and 9 mice from the 5.4 m group were assessed at 24 hours after injury,and according to the Pathologic Severity Scale of Lung Blast Injury score,they were divided into mild,moderate,and severe injury groups. The remaining mice were observed for 48-hour survival. HE staining was used to observe lung tissue injury;ELISA was used to measure the levels of inflammatory cytokines in lung tissue;Western blotting was used to measure the expression levels of GNAS,cytoskeletal components,and junctional proteins in lung tissue.
Results
2
Histological examination revealed alveolar structural disruption and fusion,intra-alveolar hemorrhage and edema,and inflammatory cell infiltration in mice with blast-induced injury in each group under a light microscope. Compared with the control group,the groups with different severities and durations of
injury had significant increases in the levels of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-α(
P
<
0.05). Compared with the control group,the groups with different severities and durations of injury had a gradual reduction in the protein expression level of GNAS(
P
<
0.05),and the groups with different severities had gradual reductions in cytoskeletal proteins(β-actin,β-tubulin),junctional proteins (E-cadherin,ZO-1),and focal adhesion kinase(FAK)(
P
<
0.05),while the groups with different durations had slight increases in β-actin,β-tubulin,ZO-1,and FAK at 6 hours,followed by gradual reductions(
P
<
0.05),as well as a gradual reduction in E-cadherin over time(
P
<
0.05).
Conclusion
2
Blast-induced lung injury in mice triggers a robust inflammatory storm,which subsequently suppresses the expression of GNAS and induces structural disruption of the alveolar epithelial cytoskeleton-junction complex,and there might be a potential positive correlation between these two phenomena.
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