κ-opioid receptor agonist U50488H alleviates acute lung injury induced by cardiopulmonary bypass rats by regulating macrophage polarization

LI Long; GAO Guangjie

doi:10.7619/jcmp.20233434

Journal of Clinical Medicine in Practice > 2024 > 28(6): 46-50. > DOI: 10.7619/jcmp.20233434

LI Long, GAO Guangjie. κ-opioid receptor agonist U50488H alleviates acute lung injury induced by cardiopulmonary bypass rats by regulating macrophage polarization[J]. Journal of Clinical Medicine in Practice, 2024, 28(6): 46-50. DOI: 10.7619/jcmp.20233434

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κ-opioid receptor agonist U50488H alleviates acute lung injury induced by cardiopulmonary bypass rats by regulating macrophage polarization

LI Long,
GAO Guangjie^,

Department of Anesthesiology, Air Force Hospital of Northern Theater Command of the People's Liberation Army, Shenyang, Liaoning, 110042

More Information

Received Date: October 28, 2023
Revised Date: January 11, 2024
Available Online: April 01, 2024

Graphical Abstract

Abstract

Abstract

Objective
To investigate whether κ-opioid receptor (KOR) agonist U50488H alleviates acute lung injury (ALI) induced by cardiopulmonary bypass (CPB) in rats by regulating macrophage polarization.
Methods
Twenty-four adult male clean grade SD rats (weight of 50 to 450 g) were randomly divided into Sham group (sham surgery), CPB group (CPB), and U50488H group (KOR agonist+CPB), with 8 rats in each group. The U50488H group was intravenously injected with 1.5 mg/kg of U50488H 30 minutes before CPB. Arterial blood gas analysis was performed at 0, 1 hour and 2 hours after CPB to calculate the alveolar-arterial oxygen gradient (A-aDO₂) and respiratory index (RI). Rats of all three groups were euthanized 2 hours after CPB cessation, and the entire right lower lobe of the lung was excised. The extravascular lung water (EVLW) was measured using the gravimetric method, and lung tissue morphology changes were observed through hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of plasma lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-4 (IL-4). Immunofluorescence was used to measure the levels of iNOS and CD206 in the lung tissue of rats.
Results
Compared to the Sham group, the CPB group of rats showed significant increases in extravascular lung water (EVLW) and levels of TNF-α, plasma IL-6 and lung tissue iNOS expression, as well as significant decreases in plasma IL-4 levels and lung tissue CD206 expression (P < 0.05). At 0, 1 hour and 2 hours after CPB, A-aDO₂, RI and LPS in the CPB group weresignificantly higher than those in the Sham group, and A-aDO₂, RI and LPS in the U50488H group were significantly lower than those in the CPB group (P < 0.05). The rats in the CPB group showed severe lung injury with alveolar congestion/bleeding and extensive infiltration of inflammatory cells, while lung injury was significantly reduced in the U50488H group.
Conclusion
The KOR agonist U50488H can promote M2 polarization of lung macrophages in rats after CPB, reduce inflammatory response, increase anti-inflammatory factor release, and thereby reducing the occurrence of ALI after CPB.
- κ-opioid receptor agonist,
- cardiopulmonary bypass,
- acute lung injury,
- macrophage polarization

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References (16)

References

[1]	HE M, ZHANG Y, XIE F, et al. Role of PI3K/Akt/NF-κB and GSK-3β pathways in the rat model of cardiopulmonary bypass-related lung injury[J]. Biomedecine Pharmacother, 2018, 106: 747-754. doi: 10.1016/j.biopha.2018.06.125
[2]	PAN T, TUOERXUN T, CHEN X, et al. The neutrophil elastase inhibitor, sivelestat, attenuates acute lung injury in patients with cardiopulmonary bypass[J]. Front Immunol, 2023, 14: 1082830. doi: 10.3389/fimmu.2023.1082830
[3]	WANG L, ZHANG H S, SUN L Y, et al. Manipulation of macrophage polarization by peptide-coated gold nanoparticles and its protective effects on acute lung injury[J]. J Nanobiotechnology, 2020, 18(1): 38. doi: 10.1186/s12951-020-00593-7
[4]	高光洁. 体外循环后大鼠肺上皮屏障功能障碍的发生机制及κ-阿片受体激动剂保护作用的研究[D]. 沈阳: 中国医科大学, 2018.
[5]	杨延章, 韩楠, 孙莹杰. κ阿片受体激动剂对体外循环术后大鼠认知功能及海马p-tau、Aβ蛋白表达的影响[J]. 实用临床医药杂志, 2023, 27(17): 105-109. doi: 10.7619/jcmp.20231349
[6]	高光洁, 宋丹丹, 孙莹杰, 等. 基质金属蛋白酶-9在大鼠心肺转流肺损伤中的作用[J]. 临床麻醉学杂志, 2013, 29(4): 397-399. https://www.cnki.com.cn/Article/CJFDTOTAL-LCMZ201304039.htm
[7]	CLARK S C. Lung injury after cardiopulmonary bypass[J]. Perfusion, 2006, 21(4): 225-228. doi: 10.1191/0267659106pf872oa
[8]	RONG J, YE S, LIANG M Y, et al. Receptor for advanced glycation end products involved in lung ischemia reperfusion injury in cardiopulmonary bypass attenuated by controlled oxygen reperfusion in a canine model[J]. ASAIO J, 2013, 59(3): 302-308. doi: 10.1097/MAT.0b013e318290504e
[9]	WANG L X, ZHANG S X, WU H J, et al. M2b macrophage polarization and its roles in diseases[J]. J Leukoc Biol, 2019, 106(2): 345-358. doi: 10.1002/JLB.3RU1018-378RR
[10]	金佳明, 张庆云, 王均伟, 等. 靶向调控肿瘤相关巨噬细胞的小分子药物研究进展[J]. 药学进展, 2023, 47(9): 644-664. https://www.cnki.com.cn/Article/CJFDTOTAL-YXJZ202309001.htm
[11]	韩笑, 王雪莲. 巨噬细胞来源的外泌体对弥漫大B细胞淋巴瘤增殖、迁移、侵袭和凋亡的影响[J]. 检验医学与临床, 2023, 20(20): 2950-2954. https://www.cnki.com.cn/Article/CJFDTOTAL-JYYL202320002.htm
[12]	候梦琳, 莫婧, 李锡清. Krüppel样因子4在肿瘤相关巨噬细胞极化中的作用机制研究进展[J]. 中国临床医生杂志, 2023, 51(3): 276-279. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLYS202303006.htm
[13]	MUÑOZ J, AKHAVAN N S, MULLINS A P, et al. Macrophage polarization and osteoporosis: a review[J]. Nutrients, 2020, 12(10): 2999. doi: 10.3390/nu12102999
[14]	ARABPOUR M, SAGHAZADEH A, REZAEI N. Anti-inflammatory and M2 macrophage polarization-promoting effect of mesenchymal stem cell-derived exosomes[J]. Int Immunopharmacol, 2021, 97: 107823. doi: 10.1016/j.intimp.2021.107823
[15]	ISAKOW W, SCHUSTER D P. Extravascular lung water measurements and hemodynamic monitoring in the critically ill: bedside alternatives to the pulmonary artery catheter[J]. Am J Physiol Lung Cell Mol Physiol, 2006, 291(6): L1118-L1131. doi: 10.1152/ajplung.00277.2006
[16]	REICHEL D, TRIPATHI M, PEREZ J M. Biological effects of nanoparticles on macrophage polarization in the tumor microenvironment[J]. Nanotheranostics, 2019, 3(1): 66-88. doi: 10.7150/ntno.30052

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κ-opioid receptor agonist U50488H alleviates acute lung injury induced by cardiopulmonary bypass rats by regulating macrophage polarization

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