Caspase-1抑制剂对大鼠急性痛风性关节炎的作用  

EFFECT OF Caspase-1 INHIBITOR ON ACUTE GOUTY ARTHRITIS IN RATS

作　　者：谷祖华[1] 苗志敏[1] 李长贵[1] 

机构地区：[1]青岛大学医学院附属医院内分泌科,山东青岛266003

出　　处：《青岛大学医学院学报》2009年第5期437-440,共4页Acta Academiae Medicinae Qingdao Universitatis

基　　金：青岛市科技局重大项目(No06-2-2-2-nsh-1)

摘　　要：目的研究Caspase-1抑制剂AC-YVAD-CMK对尿酸钠晶体诱导大鼠急性痛风性关节炎（GA）的作用。方法选用健康雄性Wistar大鼠50只,按随机区组法将大鼠分为5组：空白对照组（A组）,模型组（B组）,秋水仙碱组（C组）,低剂量AC-YVAD-CMK组（D组）,高剂量AC-YVAD-CMK组（E组）,每组10只。采用尿酸钠晶体制备大鼠GA模型,造模后给药3 d,A、B组给予生理盐水,C组给予秋水仙碱,D、E组给予不同剂量AC-YVAD-CMK。用皮尺测定造模后2、4、6、8、24、487、2 h大鼠的踝关节周径;造模后72 h,麻醉后心脏取血,生理盐水冲洗关节腔,行白细胞计数;采用放射免疫分析法测定大鼠关节冲洗液及血清中白细胞介素1β（IL-1β）的水平;以苏木精-伊红染色观察大鼠关节滑膜的病理学改变。结果造模后72 h,AC-YVAD-CMK能显著降低GA模型大鼠的踝关节肿胀度及关节冲洗液、血液白细胞水平（F=10.34-44.66,P〈0.01）。放射免疫分析检测结果显示,AC-YVAD-CMK可显著降低GA大鼠关节冲洗液及血清中IL-1β的水平（F=4.34、4.49,P〈0.01）。病理组织学检查结果显示,AC-YVAD-CMK可减轻GA模型大鼠踝关节滑膜增生,减少关节组织炎性细胞浸润。结论AC-YVAD-CMK对尿酸钠晶体诱导大鼠GA有显著的改善作用,其机制可能与降低IL-1β水平有关。Objective To study the effect of Caspas-1 inhibitor AC-YVAD-CMK on acute gouty arthritis （GA） induced by monosodium urate in rats. Methods Fifty healthy female Wistar rats were enrolled and equally randomized to five groups as： blank control （group A）, model （group B）, colchine （group C）, low-AC-YVAD-CMK （group D） and high-AC-YVAD-CMK （group E）. GA models were made using sodium urate crystal and medicating for three days： normal saline for the rats in groups A and B; colcnine for those in group C; different doses of AC-YVAD-CMK for groups D and E. The circumference of the ankle joints was measured by tape at 2 h, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after modeling. At 72 h after modeling, blood was taken from the hearts under anesthesia and the articular cavities were irrigated with normal saline, a white blood count was done. IL-1β in joint douche was detected by radioimmunoassay. Pathological changes in synovium of joint were observed with HE staining. Results At 72 h after modeling, AC-YVAI〉CMK could significantly relieve arthrocele in rat and decline leucocytes in blood and in rinse so lution of joint （F=10.34-44.66,P〈0.01）. Radio-immunoassay revealed that AC-YVAD-CMK could greatly reduce levels of IL-1β in blood and in rinse solution of joint （F=4.34,4.49;P〈0.01）. Histopathologically, AC-YVAD-CMK could abate synovium proliferation of ankle joint,reduce inflammatory cell infiltration of articlar tissue. Conclusion AC YVAD-CMK has remarkable effect on improving symptoms of acute gouty arthritis induced by monosodium urate crystals in rats,which might be related to its inhibition on levels of IL-1β.

关 键 词：AC-YVAD-CMK 尿酸 关节炎 痛风性 白细胞介素1 

分 类 号：R589.7[医药卫生—内分泌]