Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Aug 16:20:1452-60.
doi: 10.12659/MSM.890736.

Effect of ERK1/2 signaling pathway in electro-acupuncture mediated up-regulation of heme oxygenase-1 in lungs of rabbits with endotoxic shock

Yuan Zhang  1 , Jian-Bo Yu  1 , Xiao-Qing Luo  2 , Li-Rong Gong  1 , Man Wang  1 , Xin-Shun Cao  1 , Shu-An Dong  1 , Yu-Miao Yan  1 , Yihyun Kwon  3 , Jia He  4
Affiliations

Effect of ERK1/2 signaling pathway in electro-acupuncture mediated up-regulation of heme oxygenase-1 in lungs of rabbits with endotoxic shock

Yuan Zhang et al. Med Sci Monit. .

Abstract

Background: The anti-oxidative and anti-inflammatory activities of electro-acupuncture (EA), a traditional clinical method, are widely accepted, but its mechanisms are not yet well defined. In this study, we investigated the role of extracellular signal-regulated kinases1/2 (ERK1/2) pathways on electro-acupuncture - mediated up-regulation of heme oxygenase-1 (HO-1) in rabbit lungs injured by LPS-induced endotoxic shock.

Material/methods: Seventy rabbits were randomly divided into 7 groups: group C, group M, group D, group SEAM, group EAM, group EAMPD, and group PD98059. Male New England white rabbits were given EA treatment on both sides once a day on days 1-5, and then received LPS to replicate the experimental model of injured lung induced by endotoxic shock. Then, they were killed by exsanguination at 6 h after LPS administration. The blood samples were collected for serum examination, and the lungs were removed for pathology examination, determination of wet-to-dry weight ratio, MDA content, SOD activity, serum tumor necrosis factor-α, determination of HO-1 protein and mRNA expression, and determination of ERK1/2 protein.

Results: The results revealed that after EA treatment, expression of HO-1and ERK1/2 was slightly increased compared to those in other groups, accompanied with less severe lung injury as indicated by lower index of lung injury score, lower wet-to-dry weight ratio, MDA content, and serum tumor necrosis factor-α levels, and greater SOD activity (p<0.05 for all). After pretreatment with ERK1/2 inhibitor PD98059, the effect of EA treatment and expression of HO-1 were suppressed (p<0.05 for all).

Conclusions: After electro-acupuncture stimulation at ST36 and BL13, severe lung injury during endotoxic shock was attenuated. The mechanism may be through up-regulation of HO-1, mediated by the signal transductions of ERK1/2 pathways. Thus, the regulation of ERK1/2 pathways via electro-acupuncture may be a therapeutic strategy for endotoxic shock.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Comparison of the lung IQA score among the 7 groups: “a” Significantly different compared with C group (P<0.05); “b” Significantly different compared with M group (P<0.05); “c” Significantly different compared with SEAM group (P<0.05); “d” Significantly different compared with EAM group (P<0.05). Data are presented as the mean ±SD, n=10 rabbits/group.
Figure 2
Figure 2
Microphotographs of morphological changes of lung tissues (×200): Few infiltrating neutrophils were observed and there was no evidence of hemorrhage or edema in the lungs of the control group rabbits (C and PD). In the models of the lung injury induced by endotoxic shock, whether given non-acupoint treatment or given PDTC, histologic examination showed typical pathologic traits of lung injury, such as diffuse edema and severe inflammatory cell (predominantly neutrophils) infiltration in alveoli and interstitium of the lung, hemorrhage, and thickened interlobular septa (M, SEAM and EAMPD), whereas the model with electro-acupuncture treatment showed minimal lung injury, with a mild degree of neutrophil infiltration and thickening of the alveolar walls (EAM).
Figure 3
Figure 3
Comparison of lung wet/dry weight ratio (W/D): “a” Significantly different compared with C group (P<0.05); “b” Significantly different compared with M group (P<0.05); “c” Significantly different compared with SEAM group (P<0.05); “d” Significantly different compared with EAM group (P<0.05). Data are presented as the mean ±SD, n=10 rabbits/group.
Figure 4
Figure 4
Comparison of malondialdehyde (MDA): “a” Significantly different compared with C group (P<0.05); “b” Significantly different compared with M group (P <0.05); “c” Significantly different compared with SEAM group (P<0.05); “d” Significantly different compared with EAM group (P<0.05). Data are presented as the mean ±SD, n=10 rabbits/group.
Figure 5
Figure 5
Comparison of superoxide dismutase (SOD) Activity: “a” Significantly different compared with C group (P<0.05); “b” Significantly different compared with M group (P<0.05); “c” Significantly different compared with SEAM group (P<0.05); “d” Significantly different compared with EAM group (P<0.05). Data are presented as the mean ±SD, n=10 rabbits/group.
Figure 6
Figure 6
Comparison of serum tumor necrosis factor-α (TNF-α): “a” Significantly different compared with C group (P<0.05); “b” Significantly different compared with M group (P<0.05); “c” Significantly different compared with SEAM group (P<0.05); “d” Significantly different compared with EAM group (P<0.05). Data are presented as the mean ±SD, n=10 rabbits/group.
Figure 7
Figure 7
Western blot analysis of HO-1 protein: β-actin served as loading control for HO-1 protein. “a” Significantly different compared with C group (P<0.05); “b” Significantly different compared with M group (P<0.05); “c” Significantly different compared with SEAM group (P<0.05); “d” Significantly different compared with EAM group (P<0.05). Data are presented as the mean ±SD, n=10 rabbits/group.
Figure 8
Figure 8
Fluorescence quantitative PCR of HO-1mRNA: “a” Significantly different compared with C group (P<0.05); “b” Significantly different compared with M group (P<0.05); “c” Significantly different compared with SEAM group (P<0.05); “d” Significantly different compared with EAM group (P<0.05). Data are presented as the mean ±SD, n=10 rabbits/group.
Figure 9
Figure 9
Comparison of total ERK1/2 protein and p-ERK1/2 protein: β-actin served as loading control for HO-1 protein. “a” Significantly different compared with C group (P<0.05); “b” Significantly different compared with M group (P<0.05); “c” Significantly different compared with SEAM group (P<0.05); “d” Significantly different compared with EAM group (P<0.05). Data are presented as the mean ±SD, n=10 rabbits/group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Tseng TL, Chen MF, Tsai MJ, et al. Oroxylin-A Rescues LPS-Induced Acute Lung Injury via Regulation of NF-κB Signaling Pathway in Rodents. PLoS One. 2012;7:e47403. - PMC - PubMed
    1. Yang RH, Yang LN, Shen XC, et al. Suppression of NF-κB pathway by crocetin contributes to attenuation of lipopolysaccharide-induced acute lung injury in mice. Eur J Pharmacol. 2012;674:391–96. - PubMed
    1. Holst LB, Haase N, Wetterslev J, et al. Transfusion requirements in septic shock (TRISS) trial – comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial. Trials. 2013;14:150. - PMC - PubMed
    1. Chon TY, Lee MC. Acupuncture. Mayo Clin Proc. 2013;10:1141–46. - PubMed
    1. Huang CL, Huang CJ, Tsai PS, et al. Acupuncture stimulation of ST-36 (Zusanli) significantly mitigates acute lung injury in lipopolysaccharide-stimulated rats. Acta Anaesthesiol Scand. 2006;50:722–30. - PubMed

Publication types

MeSH terms