Protective effect of melatonin on formaldehyde exposure-induced acute lung injury in rats through modulation of the Nrf2 pathway
10.19405/j.cnki.issn1000-1492.2024.01.004
- Author:
Bihong Wang
1
;
Xiaoyu Nie
2
;
Weijie Ding
2
;
Jiating Zhou
2
;
Beiqi Xu
2
;
Ying Zhang
2
;
Jianguo Lv
3
;
Yanling Sun
2
Author Information
1. School of Pharmacy,Dept of Medicine,Hubei University of Science and Technology,Xianning 437100
2. School of Basic Medical Sciences,Hubei University of Science and Technology,Xianning 437100
3. School of Clinical Medical Sciences,Hubei University of Science and Technology,Xianning 437100
- Publication Type:Journal Article
- Keywords:
melatonin;
nuclear factor E2-related factor 2;
acute lung injury;
formaldehyde
- From:
Acta Universitatis Medicinalis Anhui
2024;59(1):23-28
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the protective effect of melatonin (MT) on formaldehyde (FA) inhalation-in- duced acute lung injury (ALI) in rats and its mechanism through the regulation of nuclear factor E2-related factor 2 (Nrf2) signaling pathway.
Methods :Fifty female Wistar rats were randomly divided into Control group ,FA group,FA + MT 5 mg / kg group,FA + MT 10 mg / kg group and FA + MT 20 mg / kg group,with 10 rats in each group.Except for the Control group,all other groups inhaled 3 mg / m3 FA daily for 21 d consecutively to construct the tainted model,and then treated with different MT doses for 14 d.The tainting was continued during the MT treatment.Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in lung tissue,lung water content and lung coefficient were weighed and measured,glutathione ( GSH) ,superoxide dismutase (SOD) and 8-hydroxydeoxyguanosine ( 8-OHdG) levels were measured by absorbance photometric method ,and enzyme linked immunosorbent assay(ELISA) was used to measure the levels of tumor necrosis factor-alpha (TNF-α) ,in- terleukin (IL) -6,and IL-1 β concentrations,Western blot to detect the protein expression levels of Nrf2,heme ox- ygenase-1 (HO-1) ,nuclear factor-κB ( NF-κB) ,and phosphorylated nuclear factor-κB ( p-NF-κB) in lung tis- sues,and quantitative polymerase chain reaction(qPCR) to detect the Nrf2,HO-1,and Kelch-like ECH-associated protein 1 (Keap1) mRNA expression levels.
Results :Compared with the control group,lung injury was obvious in rats in the FA group ; lung tissue GSH and SOD levels were reduced ,and 8-OHdG levels were elevated ( P < 0. 05) ; alveolar lavage fluid TNF-α , IL-6,and IL-1 β levels were elevated (P<0. 05) ; Nrf 2 and HO-1 protein expression levels were reduced in the lung tissue (P<0. 05) ,and p-NF-κB protein expression levels were was ele- vated (P<0. 05) ; the relative mRNA expression of Nrf2 and HO-1 in lung tissue was decreased,and the relative mRNA expression of Keap1 was elevated (P<0. 05) .Compared with the FA group,the lung injury of rats in the MT group was improved ; the levels of GSH and SOD in the lung tissue were increased (P<0. 05) ,and the level of 8-OHdG was decreased (P<0. 05) ; the levels of TNF-α , IL-6,and IL-1 β in the alveolar lavage fluid were de- creased (P<0. 05) ; and the expression levels of the Nrf2 and HO-1 proteins in the lung tissue were increased (P <0. 05) .p-NF-κB protein expression level was decreased (P <0. 05) ; the relative mRNA expression levels of Nrf2 and HO-1 in lung tissues were increased (P<0. 05) ,and the relative mRNA expression level of Keap1 was decreased (P<0. 05) in lung tissues,and all of them were in a dose-dependent manner.
Conclusion :MT can al- leviate oxidative stress and inflammatory responses and mitigate FA exposure-induced acute lung injury by regula- ting the Nrf2 / Keap1 / HO-1 signaling pathway.
- Full text:202406111717445491褪黑素通过调控Nrf2通路...致大鼠急性肺损伤的保护作用_王碧红.pdf