Department of Intensive Care Medicine, Dongguan Affiliated Hospital of Jinan University, Dongguan City, Guangdong Province, China.
Department of Intensive Care Medicine, Binhaiwan Central Hospital of Dongguan, Dongguan City, Guangdong Province, China.
Shock. 2023 Jun 1;59(6):966-972. doi: 10.1097/SHK.0000000000002130. Epub 2023 Apr 12.
Objectives: This study investigated the role and potential involvement of pulmonary vascular glycocalyx degradation in acute lung injury in rats with severe heatstroke (HS). Methods: Rats in an established HS model were exposed to a heated environment for 60 min in an incubator (temperature, 40°C ± 2°C; humidity, 65% ± 5%). Following pretreatment with heparanase III (HPSE III) or heparin, pathological lung injury, arterial blood gas, alveolar barrier disruption, and hemodynamic changes were evaluated. The vascular endothelial structures of the lungs were examined using electron microscopy. The concentration of Evans blue dye in the lungs and arterial blood gas were assessed. An enzyme-linked immunosorbent assay was used to quantify the plasma concentration of heparan sulfate proteoglycan. The expression of glypican-1 and syndecan-1 in pulmonary vessels was measured using immunofluorescence. Western blots were used to detect the expression of TNF-α, IL-6, and vascular endothelial biomarkers in the rat lungs. Pulmonary apoptosis was assessed using a TUNEL (terminal dUTP nick end labeling) assay, and the concentrations of malondialdehyde were measured. Results: Glycocalyx shedding aggravated lung injuries. Severe histopathological damage was observed, and indexes of lung function deviated from abnormal ranges. In addition, pulmonary vascular endothelial cells were disrupted. Compared with the HS group, the plasma concentration of heparan sulfate proteoglycan significantly increased in the HPSE group ( P < 0.05). The expression of glypican-1 and syndecan-1 decreased, and the extravasation of Evans blue dye increased ( P < 0.01). Endothelial biomarker expression increased in the lung tissue, whereas occludin expression decreased. Moreover, TNF-α and IL-6 were overexpressed following heat stress. Furthermore, apoptosis of pulmonary tissues and the concentration of malondialdehyde in rat lungs increased in the HS and HPSE groups. Conclusions : Heatstroke induced pulmonary glycocalyx degradation, which increased vascular permeability and aggravated vascular endothelial dysfunction, contributing to apoptosis, inflammation, and oxidation in the pulmonary tissues.
本研究旨在探讨严重中暑（HS）大鼠急性肺损伤中肺血管糖萼降解的作用及其潜在参与机制。方法：将大鼠置于 40°C±2°C 温度和 65%±5%湿度的孵育箱中，使其暴露于建立的 HS 模型下 60min。用肝素酶 III（HPSE III）或肝素预处理后，评估肺部病理损伤、动脉血气、肺泡屏障破坏和血流动力学变化。使用电子显微镜观察肺血管内皮结构。评估肺部和动脉血中 Evans 蓝染料的浓度。采用酶联免疫吸附试验（ELISA）检测肝素硫酸蛋白聚糖的血浆浓度。使用免疫荧光法测量肺血管中糖胺聚糖-1 和 syndecan-1 的表达。Western blot 检测大鼠肺中 TNF-α、IL-6 和血管内皮生物标志物的表达。使用 TUNEL（末端脱氧核苷酸转移酶标记）检测肺细胞凋亡，测量丙二醛浓度。结果：糖萼脱落加重了肺损伤。严重的组织病理学损伤可见，肺功能指标偏离异常范围。此外，肺血管内皮细胞被破坏。与 HS 组相比，HPSE 组的肝素硫酸蛋白聚糖血浆浓度显著增加（P<0.05）。glypican-1 和 syndecan-1 的表达减少，Evans 蓝染料渗出增加（P<0.01）。肺组织中内皮生物标志物表达增加，occludin 表达减少。此外，热应激后 TNF-α和 IL-6 过表达。此外，HS 和 HPSE 组大鼠肺组织的细胞凋亡和丙二醛浓度增加。结论：中暑导致肺糖萼降解，增加血管通透性，加重血管内皮功能障碍，导致肺组织细胞凋亡、炎症和氧化。
