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

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