肺表面活性蛋白-D在高原肺水肿发生发展中的表达及作用

doi:10.3877/cma.j.issn.2096-1537.2022.03.009

中华重症医学电子杂志 ›› 2022, Vol. 08 ›› Issue (03) : 235 -239. doi: 10.3877/cma.j.issn.2096-1537.2022.03.009

基础研究

肺表面活性蛋白-D在高原肺水肿发生发展中的表达及作用

殷志颖¹, 王皓², 李永强³, 王宇娟¹, 马世霞⁴, 马四清²^,^†(

)

^1. 810000　西宁，青海大学研究生院
^2. 810007　西宁，青海省人民医院重症医学科
^3. 810000　西宁，青海省妇女儿童医院脑外科
^4. 811600　西宁，西宁市湟中区中医院内科

收稿日期:2022-05-27 出版日期:2022-08-28
通信作者: 马四清
基金资助:
国家自然科学基金项目(81860351); 青海省高原重症医学重点实验室项目(2020-81); 高原低氧损害防治重症医学创新创业团队项目(2020-66)

Expression and effect of pulmonary surfactant protein-D in the occurrence and development of high altitude pulmonary edema

Zhiying Yin¹, Hao Wang², Yongqiang Li³, Yujuan Wang¹, Shixia Ma⁴, Siqing Ma²^,^†()

^1. Graduate School of Qinghai University, Xining 810000, China
^2. Department of Intensive Care Unit, Qinghai Provincial People's Hospital, Xining 810007, China
^3. Department of Brain Surgery, Qinghai Women's and Children's Hospital, Xining 810000, China
^4. Department of Internal Medicine, Huangzhong District Hospital of Traditional Chinese Medicine, Xining 811600, China

Received:2022-05-27 Published:2022-08-28
Corresponding author: Siqing Ma

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引用本文：

殷志颖, 王皓, 李永强, 王宇娟, 马世霞, 马四清. 肺表面活性蛋白-D在高原肺水肿发生发展中的表达及作用[J]. 中华重症医学电子杂志, 2022, 08(03): 235-239.

Zhiying Yin, Hao Wang, Yongqiang Li, Yujuan Wang, Shixia Ma, Siqing Ma. Expression and effect of pulmonary surfactant protein-D in the occurrence and development of high altitude pulmonary edema[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2022, 08(03): 235-239.

目的

探讨肺表面活性蛋白-D（SP-D）在高原肺水肿发生发展中的表达及作用。

方法

将64只Wistar雄性大鼠随机分为4组，正常对照组（16只，586 m室温饲养），低压低氧24 h、48 h及72 h组（各16只，于模拟海拔6000 m低压低氧舱内分别饲养24 h、48 h及72 h），取右侧肺组织行HE染色，观察肺组织损伤情况，收集左侧肺组织肺泡灌洗液，采用酶联免疫吸附法（ELISA）测定支气管肺泡灌洗液（BALF）中SP-D、白介素（IL）-1β、IL-6、C反应蛋白（CRP）及肿瘤坏死因子α（TNF-α）的含量。

结果

成功建造高原肺水肿动物模型；与正常对照组相比，低压低氧24、48、72 h组肺组织病理评分升高，差异有统计学意义（P＜0.05）；SP-D含量均有所下降，IL-1β、IL-6、CRP、TNF-α含量均上升，且各组间两两比较差异均有统计学意义（P＜0.05）；BALF中SP-D含量与肺组织病理评分呈负相关（r=-0.687，P＜0.05），炎症因子IL-1β、IL-6、CRP及TNF-α与肺组织病理评分均呈正相关（r=0.705，P＜0.05；r=0.728，P＜0.05；r=0.733，P＜0.05；r=0.737，P＜0.05）。

结论

SP-D在高原肺水肿的发生发展中起着一定的作用，其可能是防治高原肺水肿的新靶点。

关键词: 肺表面活性蛋白-D, 高原肺水肿, 炎症因子, 低压低氧

Objective

To investigate the expression and effect of pulmonary surfactant protein-D (SP-D) in the occurrence and development of high altitude pulmonary edema.

Methods

64 male Wistar rats were randomly divided into four groups: normal control group (n=16, 586 m altitude with room temperature feeding), low-pressure hypoxia 24 h, 48 h and 72 h group (n=16, feeding in a simulated altitude 6000 m with low-pressure hypoxia chamber for 24 h, 48 h and 72 h, respectively). The right lung tissue was used for HE staining to observe the lung tissue injury. The alveolar lavage fluid of the left lung was taken to measure the SP-D, IL-1β, IL-6, CRP and TNF-α by enzyme-linked immunosorbent assay.

Results

The animal model of high-altitude pulmonary edema was successfully established. Compared with the control group, the pathological scores of lung tissue in the 24, 48 and 72 h hypoxia groups were increased. The protein expression of SP-D was decreased while IL-1β, IL-6, CRP and TNF-α were increased significantly (P＜0.05). SP-D in alveolar lavage fluid was negatively correlated with lung histopathological score (r=-0.687, P＜0.05). Inflammatory factors IL-1β, IL-6, CRP and TNF-were positively correlated with lung histopathological score (r=0.705, P＜0.05; r=0.728, P＜0.05; r=0.733, P＜0.05; r=0.737, P＜0.05).

Conclusion

SP-D plays a important role in the occurrence and development of high altitude pulmonary edema, which may be a new target for the prevention and treatment.

Key words: Pulmonary surfactant protein-D, High altitude pulmonary edema, Inflammatory factor, Low-pressure hypoxia

图1 各组间肺组织病理学改变比较（HE，×100）。图a为正常对照组，结构清楚，未见充血肿胀；图b为H24 h组，肺泡壁增厚，可见少量红细胞；图c为H48 h组，肺泡壁较24 h组增厚，部分肺泡壁破裂融合成腔；图d为H72 h组，肺泡壁增厚，毛细血管充血，镜下可见有出血

表1 各组间BALF中SP-D及各炎症指标水平比较（

x ˉ

±s）

组别	只数	SP-D（pg/ml）	IL-1β（pg/ml）	IL-6（pg/ml）	CRP（ng/ml）	TNF-α（pg/ml）
正常对照组	16	32.41±2.67	13.80±3.02	82.16±8.47	15.84±2.45	162.80±12.24
H24 h组	16	27.26±2.79^a	24.23±2.93^a	126.56±8.93^a	31.77±2.75^a	226.73±14.26^a
H48 h组	16	17.83±2.35^ab	36.63±3.84^ab	159.99±14.55^ab	55.08±2.98^ab	280.14±17.93^ab
H72 h组	16	13.25±1.29^abc	53.30±4.74^abc	196.12±18.88^abc	83.90±2.92^abc	366.17±21.47^abc
F值		212.484	328.524	56.701	1749.291	408.150
P值		＜0.01	＜0.01	＜0.01	＜0.01	＜0.01

表1 各组间BALF中SP-D及各炎症指标水平比较（

x ˉ

±s）

组别	只数	SP-D（pg/ml）	IL-1β（pg/ml）	IL-6（pg/ml）	CRP（ng/ml）	TNF-α（pg/ml）
正常对照组	16	32.41±2.67	13.80±3.02	82.16±8.47	15.84±2.45	162.80±12.24
H24 h组	16	27.26±2.79^a	24.23±2.93^a	126.56±8.93^a	31.77±2.75^a	226.73±14.26^a
H48 h组	16	17.83±2.35^ab	36.63±3.84^ab	159.99±14.55^ab	55.08±2.98^ab	280.14±17.93^ab
H72 h组	16	13.25±1.29^abc	53.30±4.74^abc	196.12±18.88^abc	83.90±2.92^abc	366.17±21.47^abc
F值		212.484	328.524	56.701	1749.291	408.150
P值		＜0.01	＜0.01	＜0.01	＜0.01	＜0.01

图2 BALF中细胞因子含量与肺病理评分的相关性分析。图a为SP-D含量与肺病理评分的相关性；图b为IL-1β与肺病理评分的相关性；图c为IL-6与肺病理评分的相关性；图d为CRP与肺病理评分的相关性；图e为TNF-α与肺病理评分的相关性注：BALF为支气管肺泡灌洗液；SP-D为肺表面活性蛋白-D；IL为白介素；CRP为C反应蛋白；TNF-α为肿瘤坏死因子α

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