Abstract: Objective To observe the effect of type I diabetes induced by streptozotocin （STZ） on inflammatory arthritis in mice. Methods Sixteen SPF grade 6 weeks old male C57BL/6J mice were randomly divided into two groups, with 8 mice in each group. At the age of 6 weeks, the diabetic mice model was established by intraperitoneal injection of 150 mg/kg streptozotocin, while the control group was injected with the same volume of citrate buffer. At the age of 7 weeks, mouse arthritis model of two groups was established by foot pad injection of 0.5 ml complete emulsifier of bovine type Ⅱ collagen and Freund's adjuvant at both sides of hide foots. The electronic vernier caliper was used to measure the thickness of foot. The mRNA expression levels of OPG and RANKL genes in ankle joints of two groups of mice were detected by real-time qPCR. The protein expression levels of OPG and RANKL in ankle joints were detected by Western blot. Results Compared with CON group, fasting blood glucose increased in STZ group （P<0.001）, and a diabetes model was successfully established. After the establishment of CIA model, red, swelling and joint movement disorder were observed in both hind feet of mice, and arthritis developed faster in CON+CIA group, and the difference was statistically significant at week 2 and 3 （P<0.05）. RT-qPCR and Western blot results showed that compared with CON+CIA group, the expressions of OPG and RANKL in joint tissues of mice in STZ+CIA group were significantly increased （P<0.01）. The RANKL/OPG ratio >1 indicated that the process of bone resorption was significantly higher than that of bone formation. Conclusion In the collagen-induced inflammatory arthritis model mice, although the non-diabetic mice developed faster arthritis and more severe swelling, the diabetic mice had longer duration of arthritis and more severe bone resorption. However, the specific mechanism of hyperglycemia on arthritis remains to be further researched.

Key words: streptozotocin, bovine type Ⅱ collagen, freund's adjuvant, mouse diabetes model, mouse arthritis model, osteoprotegerin, RANKL

摘要： 目的 探讨链脲佐菌素（STZ）诱导的Ⅰ型糖尿病模型对小鼠炎症性关节炎的影响。方法 将16只6周龄SPF级雄性C57BL/6J小鼠随机分成两组,每组8只。糖尿病组小鼠采用于6周龄时一次性腹腔注射链脲佐菌素150 mg/kg建立小鼠Ⅰ型糖尿病模型;对照组注射同等体积柠檬酸盐缓冲液。在7周龄时对两组小鼠均于双侧后足足垫注射牛Ⅱ型胶原和完全弗氏佐剂的完全乳化剂,每只足0.5 mL建立小鼠关节炎模型。采用电子游标卡尺测量小鼠双足足趾厚度。采用实时荧光定量PCR检测两组小鼠踝关节OPG、RANKL基因mRNA的表达水平。采用western blot检测踝关节OPG、RANKL的蛋白表达水平。结果 与CON组比较,STZ组小鼠空腹血糖升高（P<0.001）,成功建立糖尿病模型。CIA模型建立后,小鼠双侧后足均出现明显红、肿和关节运动障碍,且CON+CIA组小鼠关节炎发展较快,在第2、3周时差异有统计学意义（P<0.05）。RT-qPCR和Western blot结果显示,与CON+CIA组相比,STZ+CIA组小鼠关节组织中OPG、RANKL表达明显升高,差异具有统计学意义（P<0.01）。且RANKL/OPG比值>1,表明骨吸收过程显著高于骨生成过程。结论 在胶原诱导炎症性关节炎模型小鼠中,虽然非糖尿病小鼠的关节炎发展更快、肿胀程度更严重,而糖尿病小鼠关节炎持续时间更长,且骨吸收过程更严重。

关键词: 链脲佐菌素, 牛Ⅱ型胶原, 弗氏佐剂, 糖尿病模型小鼠, 关节炎模型小鼠, OPG, RANKL