Therapeutic effects of carbon monoxide-saturated hemoglobin-loaded oxygen carrier on idiopathic pulmonary fibrosis in mice
10.13303/j.cjbt.issn.1004-549x.2026.04.009
- VernacularTitle:一氧化碳血红蛋白携氧载体对特发性肺纤维化小鼠的作用研究
- Author:
Peichen XU
1
;
Shen LI
1
;
Wanjin LI
1
;
Hong WANG
1
;
Jiaxin LIU
1
;
Ye CAO
1
;
Rui ZHONG
1
Author Information
1. Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China
- Publication Type:Journal Article
- Keywords:
idiopathic pulmonary fibrosis;
carbon monoxide-loaded hemoglobin-based oxygen carrier;
complement and coagualation cascades
- From:
Chinese Journal of Blood Transfusion
2026;39(4):478-485
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.
