Shi Min, Cui Fang, Liu Ai-Jing, Li Jiao, Ma Hui-Juan, Cheng Ming, Yang Jing, Zhang Yi
Department of Physiology, Hebei Medical University, Shijiazhuang, China.
Sheng Li Xue Bao. 2011 Apr 25;63(2):115-23.
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.
本研究旨在探讨慢性间歇性低压低氧（CIHH）对大鼠胶原诱导性关节炎（CIA）的影响。将50只成年雄性Sprague-Dawley大鼠随机分为5组：CIHH预处理组（Pre-T）、预处理对照组（Pre-C）、CIHH后处理组（Post-T）、后处理对照组（Post-C）和空白对照组（Con）。Pre-T组和Post-T组大鼠分别在CIA诱导前和诱导后12天，于低压舱内暴露于28天的低压低氧环境（模拟海拔3000米，每天5小时，pO2 = 108.8 mmHg，O2含量14%）。Pre-C组和Post-C组大鼠仅经历CIA诱导，分别作为Pre-T组和Post-T组的对照组。Con组大鼠未接受任何处理。用螺旋测微器测量大鼠双后足厚度，通过关节炎指数（AI）评估关节炎程度。通过苏木精-伊红（HE）染色观察踝关节的形态学变化。采用末端脱氧核苷酸转移酶介导的缺口末端标记法（TUNEL）检测滑膜组织中的凋亡率，用流式细胞术检测脾脏中CD3(+) T淋巴细胞的凋亡率。采用免疫组织化学SP法检测Bcl-2和Bax的蛋白表达。结果显示，Pre-T组大鼠的CIA发病率低于Pre-C组大鼠（P < 0.05）。Pre-T组和Post-T组大鼠的AI分别小于Pre-C组和Post-C组（P < 0.05）。在Pre-C组和Post-C组大鼠中，踝关节出现滑膜细胞增生、血管翳形成、炎性细胞浸润以及软骨和骨破坏。相反，Pre-T组和Post-T组大鼠踝关节的病理变化明显减轻。与Pre-C组和Post-C组大鼠相比，Pre-T组和Post-T组大鼠滑膜细胞和T淋巴细胞的凋亡率升高（P < 0.05）。关于可能的抗凋亡机制，无论在CIA诱导前还是诱导后，CIHH均可使关节滑膜细胞和脾脏T淋巴细胞中的Bcl-2表达降低，Bax表达升高（P < 0.05）。综上所述，CIHH通过增强滑膜细胞和T淋巴细胞的凋亡对大鼠CIA具有保护作用，这可能与抑制Bcl-2蛋白表达和促进Bax蛋白表达有关。
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