title: Protection of chronic intermittent hypobaric hypoxia against collagen-induced arthritis in rat through increasing apoptosis.
abstract: The aim of present study was to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on collagen-induced arthritis (CIA) in rat. Fifty male adult Sprague-Dawley rats were randomly divided into 5 groups: CIHH pre-treatment group (Pre-T), pre-control group (Pre-C), CIHH post-treatment group (Post-T), post-control group (Post-C) and blank control group (Con). The rats in Pre-T and Post-T groups were exposed to 28 d of hypobaric hypoxia (simulated 3 000 m altitude, 5 h per day, pO2 = 108.8 mmHg, 14% O2) in a hypobaric chamber before and 12 days after CIA induction, respectively. The rats in Pre-C and Post-C groups were only experienced CIA induction, being control groups for Pre-T and Post-T groups, respectively. The rats in Con group were not given any treatment. The thickness of two-hind paw of rat was measured with spiral micrometer and the degree of arthritis was evaluated by arthritis index (AI). Morphological changes of ankle joint were observed through HE staining. The apoptotic rate in synovial tissue was measured by terminal dUTP nick end labeling (TUNEL) and the apoptotic rate of CD3(+) T lymphocyte in spleen was measured by flow cytometry technique. The protein expressions of Bcl-2 and Bax were measured using immunohistochemistry SP method. The results showed that incidence rate of CIA in Pre-T rats was lower than that in Pre-C rats (P < 0.05). AI in Pre-T and Post-T rats were smaller than those in Pre-C and Post-C, respectively (P < 0.05). In Pre-C and Post-C rats, there were hyperplasia of synovial cell, pannus forming, infiltration with inflammatory cell, and destroyed cartilage and bone in ankle joint. On the contrary, pathological changes of ankle joint were alleviated significantly in Pre-T and Post-T rats. Compared with Pre-C and Post-C rats, apoptotic rates of synovial cell and T lymphocyte in Pre-T and Post-T rats were increased (P < 0.05). As to the possible anti-apoptosis mechanism, CIHH, no matter before and after CIA induction, decreased Bcl-2 expression and increased Bax expression in joint synovial cells and spleen T lymphocytes (P < 0.05), respectively. In conclusion, CIHH possesses a protective effect against CIA in rat by enhancing apoptosis of synovial cells and T lymphocytes, which may be related to the inhibition of Bcl-2 protein expression and the promotion of Bax protein expression.
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Fang
authors.initials: F
authors.lastname: Cui
authors.forename: Ai-Jing
authors.initials: AJ
authors.lastname: Liu
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Ma
authors.forename: Ming
authors.initials: M
authors.lastname: Cheng
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000860:Hypoxia / Q000503:physiopathology*; D057775:Ischemic Postconditioning / Q000379:methods*; D019194:Ischemic Preconditioning / Q000379:methods*; D007596:Joints / Q000473:pathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology; D013583:Synovial Membrane / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein