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[关节腔内注射p38丝裂原活化蛋白激酶抑制剂对骨关节炎大鼠模型关节软骨基质金属蛋白酶的影响]

[Effects of intra-articular injection of p38 mitogen-activated protein kinase inhibitor on matrix metalloproteinase in articular cartilage of a rat model of osteoarthritis].

作者信息

Chen Wei-Dong, Jiang Qing, Chen Dong-Yang, Xu Hua, Zhang Ya-Feng

机构信息

Center of Diagnosis and Treatment for Joint Disease, Nanjing Gulou Hospital, Medical School of Nanjing University, Nanjing 210008, China.

出版信息

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2007 Dec;29(6):777-81.

PMID:18595258
Abstract

OBJECTIVE

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.

METHODS

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).

CONCLUSION

SB203580 can inhibit the expressions of MMP-3 and MMP-13 and thus protect the cartilage.

摘要

目的

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。

方法

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)。

结论

SB203580可抑制MMP-3和MMP-13的表达,从而保护软骨。

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