Chen Wei-Dong, Jiang Qing, Chen Dong-Yang, Xu Hua, Zhang Ya-Feng
Center of Diagnosis and Treatment for Joint Disease, Nanjing Gulou Hospital, Medical School of Nanjing University, Nanjing 210008, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2007 Dec;29(6):777-81.
To observe the effect of intra-articular injection of SB203580, a selective p38 mitogen-activated protein kinase inhibitor, on the expression of matrix metalloproteinase (MMP)-3, MMP-13 in a rat model of osteoarthritis (OA) and to explore the relationship between the MMP-3/MMP-13 expressions and the severity of OA.
Fourty SD rats underwent unilateral anterior cruciate ligament transection (ACLT) and then randomly divided into four groups, with 10 rats in each group. Group A received 0.1 ml intra-articular injection of SB203580 at a high concentration of 100 micromol/L (once a week) immediately after surgery, and group B were treated under the same condition using SB203580 with a low concentration of 10 micromol/ L Group C received 0.1 ml intra-articular normal saline, and group D were not injected as controls after ACLT. All rats were sacrificed seven weeks after the surgery. Macroscopic and immunohistochemical studies were performed on the cartilage. Protein expressions of MMP-3 and MMP-13 were determined by Western blot. RESULTS Cartilage degradation was significantly milder in group A and group B than in the control groups, as shown by morphological studies (P < 0. 05) and immunohistochemical studies (P < 0. 05). The protein expressions of MMP-3 and MMP-13 in cartilage were significantly lower in groups A and B than in groups C and D (P < 0.01).
SB203580 can inhibit the expressions of MMP-3 and MMP-13 and thus protect the cartilage.
观察关节腔内注射选择性p38丝裂原活化蛋白激酶抑制剂SB203580对骨关节炎(OA)大鼠模型中基质金属蛋白酶(MMP)-3、MMP-13表达的影响,并探讨MMP-3/MMP-13表达与OA严重程度之间的关系。
40只SD大鼠行单侧前交叉韧带切断术(ACLT),然后随机分为4组,每组10只。A组于术后立即关节腔内注射高浓度100μmol/L的SB203580 0.1 ml(每周1次),B组用低浓度10μmol/L的SB203580在相同条件下治疗,C组关节腔内注射0.1 ml生理盐水,D组ACLT后不注射作为对照。术后7周处死所有大鼠。对软骨进行大体和免疫组化研究。通过蛋白质印迹法测定MMP-3和MMP-13的蛋白表达。结果:形态学研究(P<0.05)和免疫组化研究(P<0.05)显示,A组和B组软骨退变明显轻于对照组。A组和B组软骨中MMP-3和MMP-13的蛋白表达明显低于C组和D组(P<0.01)。
SB203580可抑制MMP-3和MMP-13的表达,从而保护软骨。