The protective effects of chronic intermittent hypobaric hypoxia pretreatment against collagen-induced arthritis in rats

Min Shi; Fang Cui; Ai-Jing Liu; Hui-Jie Ma; Ming Cheng; Shu-Xia Song; Fang Yuan; De-Pei Li; Yi Zhang

doi:10.1186/s12950-015-0068-1

The protective effects of chronic intermittent hypobaric hypoxia pretreatment against collagen-induced arthritis in rats

J Inflamm (Lond). 2015 Mar 25:12:23. doi: 10.1186/s12950-015-0068-1. eCollection 2015.

Authors

Min Shi¹, Fang Cui², Ai-Jing Liu³, Hui-Jie Ma², Ming Cheng², Shu-Xia Song⁴, Fang Yuan², De-Pei Li⁵, Yi Zhang⁶

Affiliations

¹ Department of Physiology, Hebei Medical University, Shijiazhuang, 050017 China ; Department of Clinical Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang, 050017 China.
² Department of Physiology, Hebei Medical University, Shijiazhuang, 050017 China.
³ Department of Immune and Rheumatism, The Second Hospital of Hebei Medical University, Shijiazhuang, 050017 China.
⁴ Department of Immunology, Hebei Medical University, Shijiazhuang, 050017 China.
⁵ Department of Critical Care, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030 USA.
⁶ Department of Physiology, Hebei Medical University, Shijiazhuang, 050017 China ; Hebei Key Laboratory of Medical Biotechnology, Shijiazhuang, 050017 China ; Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Shijiazhuang, Hebei 050000 PR China.

Abstract

Objective: To explore the immunological mechanisms underlying the effect of chronic intermittent hypobaric hypoxia (CIHH) pretreatment on collagen-induced arthritis (CIA) in rat.

Methods: Fifty-four adult male Sprague-Dawley rats were used in the experiment. Arthritis in CIA rats (n=18) was induced by injection of collagen. The CIHH+CIA rats (n=18) were treated with CIHH (simulated 3000 m altitude, 5 hours per day for 28 days, PO2=108.8 mmHg) before CIA. The control rats (n=18) were not given any treatment.

Results: (1) Incidence rate of CIA in CIHH+CIA rats was significantly lower than that in CIA rats (P<0.05). (2) The paw thickness and arthritis index (AI) value in CIHH+CIA rats were lower than those in CIA rats (P<0.05). (3) The hyperplasia with inflammatory infiltration in synovial tissue of joints in CIHH+CIA rats was much alleviative compared with CIA rats. (4) TNF-α, IFN-γ, IL-4 and IL-17 in synovial tissue of joint and serum in CIHH+CIA rats were decreased compared with CIA rats (P<0.05). (5) The number of CD4-positive T-lymphocytes and the ratio of CD4/CD8 T-lymphocytes in peripheral blood in CIHH+CIA rats were lower than those in CIA rats (P<0.05). (6) The protein expression of HIF-1α and NF-κB in synovial tissue of joint in CIHH+CIA rats was decreased compared with CIA rats (P<0.05).

Conclusion: CIHH pretreatment has a protective effect against collagen-induced arthritis in rat through down-regulation of HIF-1α and NF-κB, inhibition of inflammatory cytokines TNF-α and IL-17, and balance in CD4/CD8 and Th1/Th2 T lymphocytes.

Keywords: Chronic intermittent hypobaric hypoxia; HIF-1α; NF-κB; Rat; Rheumatoid arthritis; T lymphocytes; Th1/Th2.