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本文旨在研究慢性间歇性低压低氧(chronic intermittent hypobaric hypoxia,CIHH)对大鼠胶原诱导性关节炎(collagen-induced arthritis,CIA)的影响。雄性成年Sprague-Dawley大鼠50只,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)及空白对照组(Con)。Pre-T和Post-T大鼠分别在CIA造模前和造模开始后第12天给予28d模拟海拔3000m(pO2=108.8mmHg,14%O2)、每天5h的CIHH处理;Pre-C和Post-C不接受CIHH处理,CIA造模处理分别与Pre-T和Post-T相同;Con大鼠不给予任何处理。通过螺旋测微器测定大鼠双后足爪厚度,以关节炎指数(ar-thritis index,AI)评价关节炎程度;HE染色法观察踝关节组织形态学变化;原位末端标记法(TUNEL)检测膝关节滑膜组织细胞凋亡率;流式细胞术检测脾脏CD3+T淋巴细胞凋亡率;免疫组化SP法检测滑膜细胞和脾脏淋巴细胞Bcl-2、Bax蛋白表达水平。结果显示:(1)Pre-T大鼠CIA发生率明显低于Pre-C组大鼠(P<0.05);Pre-T和Post-T组大鼠的AI值分别明显低于Pre-C和Post-C组大鼠(P<0.05)。(2)Pre-C及Post-C大鼠踝关节滑膜细胞明显增生,形成血管翳,侵蚀软骨及骨,炎细胞浸润增加;Pre-T和Post-T大鼠关节组织病理改变明显减轻。(3)Pre-T和Post-T大鼠滑膜细胞及脾脏淋巴细胞的凋亡率分别较Pre-C及Post-C大鼠明显增加(P<0.05)。(4)与Pre-C及Post-C大鼠相比较,Pre-T和Post-T动物滑膜组织细胞及脾脏淋巴细胞Bcl-2蛋白表达明显降低(P<0.05),而Bax蛋白表达则明显升高(P<0.05)。以上结果表明,CIHH可通过抑制Bcl-2蛋白和增强Bax蛋白表达,促进关节滑膜细胞和淋巴细胞凋亡,从而发挥抗大鼠CIA作用。
This article aims to investigate the effects of chronic intermittent hypobaric hypoxia (CIHH) on collagen-induced arthritis (CIA) in rats. Fifty male adult Sprague-Dawley rats were randomly divided into five groups: Pre-T CI, Pre-C, Post-T CIHH, (Post-C) and blank control group (Con). Pre-T and Post-T rats were given CIHH at a simulated altitude of 3000m (pO2 = 108.8mmHg, 14% O2) for 28 days before CIA and at 12th day after modeling respectively. Pre-C and Post -C did not receive CIHH treatment, CIA modeling treatment with Pre-T and Post-T the same; Con rats without any treatment. The thickness of the rat double hind paw was measured by a spiral micrometer, the degree of arthritis was evaluated by the arthritis index (AI), the morphological changes of the ankle were observed by HE staining, the TUNEL The apoptotic rate of synovial tissue in knee joint was measured. The apoptosis rate of CD3 + T lymphocytes in spleen was detected by flow cytometry. The expression of Bcl-2 and Bax protein in synovial cells and spleen lymphocytes was detected by immunohistochemical SP method. The results showed that: (1) The incidence of CIA in Pre-T rats was significantly lower than that in Pre-C rats (P <0.05); AI values in Pre-T and Post-T rats were significantly lower than those in Pre-C and Pre- Post-C rats (P <0.05). (2) The hyperplasia of ankle synovial cells in Pre-C and Post-C rats resulted in the formation of angiostenosis, erosion of cartilage and bone, and increased infiltration of inflammatory cells. The pathological changes of joint tissue in Pre-T and Post-T rats were significantly reduced. (3) The apoptotic rate of Pre-T and Post-T rats synovial cells and spleen lymphocytes were significantly increased compared with Pre-C and Post-C rats (P <0.05). (4) Compared with Pre-C and Post-C rats, the expression of Bcl-2 protein in pre-T and Post-T animal synovial tissue cells and splenic lymphocytes was significantly decreased (P <0.05), while the expression of Bax protein Was significantly higher (P <0.05). These results suggest that CIHH exerts anti-rat CIA effect by inhibiting Bcl-2 protein and enhancing Bax protein expression, promoting synoviocyte and lymphocyte apoptosis.