新生血管生成抑制剂治疗膝骨性关节炎大鼠的疗效研究

Experimental treatment of knee osteoarthritis with angiogenesis inhibitor sunitinib in rats

目的探讨新生血管生成抑制剂舒尼替尼治疗膝骨性关节炎(KOA)大鼠的疗效,为防治KOA新类药物的研发提供实验基础。方法将32只SD大鼠随机分成4组,即空白组(不造模,不给药)、治疗4周组(KOA造模后灌胃舒尼替尼1mg·kg^(-1)·d^(-1),持续4周)、治疗8周组(KOA造模后灌胃舒尼替尼1mg·kg^(-1)·d^(-1),持续8周)及对照组(KOA造模后灌胃同等体积的0.9%氯化钠溶液),每组8只。实验结束后处死大鼠,收集关节液标本,采用ELISA法检测并比较4组大鼠关节液中血管内皮生长因子(VEGF)、基质金属蛋白酶13(MMP-13)的表达水平。结果对照组、治疗4周组、治疗8周组大鼠关节液中VEGF、MMP^(-1)3表达水平分别为(237.95±69.1)、(168.43±47.47)、(136.75±27.48)pg·ml^(-1)和(94.98±37.63)、(75.43±20.23)、(68.54±19.82)pg·ml^(-1);2个治疗组与对照组比较,关节液中VEGF、MMP-13表达水平均明显降低(均P<0.01);治疗4周组与治疗8周组比较,差异均无统计学意义(均P>0.05)。结论新生血管生成抑制剂舒尼替尼能有效降低关节液中VEGF、MMP-13表达水平,长期用药可将VEGF和MMP-13的表达维持在较低水平,从而达到防治KOA的作用。

Objective To explore the curative effect of angiogenesis inhibitor sunitinib in treatment of knee osteoarthritis(KOA) in rats. Methods Thirty two SD rats were randomly divided into 4 groups: control group, model group, 4 w-treatment group and 8 w-treatment group with 8 in each group. KOA model was induced by intra-articular injection of 4% papain in rats,sunitinib(1 mg·kg^(-1)·d^(-1)) was given by gavage after modeling for 4 or 8 weeks in 4 w-treatment group and 8 w-treatment group,respectively. The rats were sacrificed at the end of the experiment, and VEGF and MMP-13 levels in synovial fluid were detected by ELISA. Results The VEGF levels in synovial fluid of model group, 4 w-treatment and 8 w-treatment groups were 237.95±69.1, 168.43±47.47 and 136.75±27.48 pg·ml^(-1), respectively(P<0.01). The levels of MMP-1 were 94.98±37.63, 75.43±20.23 and 68.54±19.82 pg·ml^(-1), respectively(P<0.01). There were no significant difference in VEGF and MMP-1 levels in joint fluid between 4 w-and 8 w-treatment groups(P >0.05). Conclusion Angiogenesis inhibitor sunitinib can effectively inhibit VEGF and MMP-13 contents in the joint fluid of rats with knee osteoarthritis, indicating that long-term medication of sunitinib may be of value in prevention and treatment of the KOA.