CAJ | 학술논문

目的：以胶原诱导关节炎（CIA）大鼠为模型，观察辛伐他汀对其血清细胞因子及滑膜组织天冬氨酸蛋白水解酶-3（Caspase-3）表达的影响，探索辛伐他汀治疗类风湿关节炎的可能机制。方法使用牛Ⅱ型胶原建立CIA模型，将造模成功的大鼠（16只）均分为模型组及药物组，未造模者（7只）为对照组。药物组用2.0 mg/（kg·d）灌胃，对照组和模型组用无菌注射用水5 mL/（kg·d）灌胃。记录大鼠关节炎评分（AI）和足趾容积，每周1次；初次免疫后第42天，眼内眦取血采用ELISA法检测各组血清肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6水平，处死大鼠取后肢踝关节进行HE染色，并用免疫组织化学检测滑膜组织Caspase-3表达。结果药物组和模型组AI在初次免疫后21 d开始下降，35 d后药物组均低于模型组（均P＜0.05）。2组足趾容积于初次免疫14 d后缓慢下降，但仍明显高于对照组；35、42 d时药物组均低于模型组（均P＜0.05）。初次免疫后42 d，药物组TNF-α和IL-6水平均低于模型组，高于对照组（均P＜0.05）。药物组较模型组踝关节滑膜组织增生明显减轻，仅有少量炎细胞浸润，Caspase-3的表达明显上调。结论辛伐他汀可明显抑制CIA大鼠血清TNF-α、IL-6的分泌，上调滑膜组织Caspase-3的表达及减轻滑膜组织增生。
목적：이효원유도관절염（CIA）대서위모형，관찰신벌타정대기혈청세포인자급활막조직천동안산단백수해매-3（Caspase-3）표체적영향，탐색신벌타정치료류풍습관절염적가능궤제。방법사용우Ⅱ형효원건립CIA모형，장조모성공적대서（16지）균분위모형조급약물조，미조모자（7지）위대조조。약물조용2.0 mg/（kg·d）관위，대조조화모형조용무균주사용수5 mL/（kg·d）관위。기록대서관절염평분（AI）화족지용적，매주1차；초차면역후제42천，안내자취혈채용ELISA법검측각조혈청종류배사인자（TNF）-α、백세포개소（IL）-6수평，처사대서취후지과관절진행HE염색，병용면역조직화학검측활막조직Caspase-3표체。결과약물조화모형조AI재초차면역후21 d개시하강，35 d후약물조균저우모형조（균P＜0.05）。2조족지용적우초차면역14 d후완만하강，단잉명현고우대조조；35、42 d시약물조균저우모형조（균P＜0.05）。초차면역후42 d，약물조TNF-α화IL-6수평균저우모형조，고우대조조（균P＜0.05）。약물조교모형조과관절활막조직증생명현감경，부유소량염세포침윤，Caspase-3적표체명현상조。결론신벌타정가명현억제CIA대서혈청TNF-α、IL-6적분비，상조활막조직Caspase-3적표체급감경활막조직증생。
Objective To evaluate therapeutic effects of simvastatin on serum expressions of cytokines and synovial tissue aspartic protease-3 (Caspase-3) in collagen induced arthritis (CIA) in rats, and the mechanism thereof. Methods The rat model of CIA was established by injecting bovine Ⅱ collagen. Sixteen model rats were randomly divided into two groups:CIA model group (sterile water 5 mL·kg-1·d-1 by gavage) and simvastatin group (2.0 mg·kg-1·d-1 by gavage). Seven normal rats were included in control group (sterile water 5 mL·kg-1·d-1 by gavage). The arthritis index (AI) and hind paw vol-umes were recorded once a week. The serum levels of cytokine, tumor necrosis factor (TNF)-αand interleukin (IL)-6 were measured by ELISA 42 days after the initial immunization. The expression of Caspase-3 in ankle synovial tissue was detect-ed by immunohistochemical method, and pathological results of HE staining in rat ankle were compared between three groups. Results Values of AI were decreased on the 24-d of the initial immunization in simvastatin group and CIA model group, which was significantly decreased on the 35-d of the initial immunization in simvastatin group than that of CIA model group (P<0.05). The values of hind paw volumes were decreased on the 14-d of the initial immunization in simvastatin group and CIA model group, which was still significantly higher than those of control group (P<0.05). The values of hind paw volumes were decreased on the 35-d and 42-d of the initial immunization in simvastatin group than those of CIA model group (P<0.05). The serum levels of TNF-αand IL-6 on the 42-d of the initial immunization were significantly lower in simvastatin group than those of CIA model group, but which were significantly higher than those of control group ( P<0.05). There were more synovial hyperplasia in simvastatin group than those of CIA model group. Only a small amount of inflamma-tory cell infiltration was found in simvastatin group. The expression of Caspase-3 was significantly higher in simvastatin group than that of CIA model group. Conclusion Simvastatin can significantly inhibit the serum levels of TNF-αand IL-6 in CIA model rats, and can up-regulate the expression of Caspase-3 in ankle of model rats.