关节内注射BMP-7影响骨关节炎进展的实验研究

目的拟应用骨形态发生蛋白-7（BMP-7）进行关节内注射干预骨关节炎的动物模型，观察和判断BMP-7关节内注射对于家兔骨关节炎进展的影响，为临床对于骨关节炎的防治提供新的方法和思路。方法拟选用雄性新西兰大白兔15只，体重2．8～3．2kg，平均3kg，双侧后腿膝关节采用ALCT方法联合内侧半月板前1／3切除建立骨关节炎模型后，取右膝关节作为实验组进行每周关节内定量注射BMP-7，左膝关节作为空白对照组不予处置，分别于4、8、12周各取5只实验兔双侧后腿膝关节进行观察对比，对骨关节炎关节软骨组织形态学观察和评分，通过对于病变明显部位进行病理切片、甲苯胺蓝染色观察关节软骨的退变情况，所得结果采用国际骨关节炎研究协会（OARSI）骨关节炎软骨组织病理分级制度进行评分及对比，通过免疫组化检测Ⅱ型胶原的表达情况。结果进行BMP-7关节内注射4、8、12周后实验组组织形态学评分以及病理切片苯胺蓝染色国际骨关节炎研究协会（OARSI）骨关节炎软骨组织病理分级制度评分均优于对照组，Ⅱ型胶原持续表达情况实验组明显高于对照组。结论关节内注射BMP-7可以减缓骨关节炎的病情进展。

The experimental study of the effect of intra-articular injections of bone morphogenetic protein-7 on the progress of osteoarthritis

Objective To observe and estimate the effect of intra-articular injections of bone morphogenetic protein-7 （BMP-7） on the progress of rabbit osteoarthritis, using animal models of osteoarthritis treated by intra- articular injections of BMP-7, so as to provide new method and thinking for clinical prevention and treatment. Methods 15 male New Zealand white rabbits weighing an average of 3kg （range; 2.8-3.2kg） were chosen for the experiment. Animals underwent anterior cruciate ligament transection （ALCT） and resection of the anterior 1/3 of medial meniscus in the knee joints of bilateral hind legs, forming the model group with osteoarthritis. Weekly intra-articular injections of BMP-7 were performed in the right legs, and the left legs were taken as the control group. The knee joints of bilateral hind legs of 5 rabbits were chosen and observed comparatively at the 4th, 8th, and 12th weeks respectively. Histomorphological observation and grading of the articular cartilage were carried out. The pathological sections in significant lesion sites and aniline blue staining were used to observe articular cartilage degeneration. The results were graded and compared according to the cartilage tissue pathology classification system of the International Osteoarthritis Research Association （OARSI）, and the expression of type Ⅱ collagen was detected by immunohistochemistry. Results Comparing with that of the control group, the histomorphological grades, pathological sections and aniline blue staining according to the cartilage tissue pathology classification system of OARSI for the rabbits in the experimental group receiving intra-articular injections of BMP-7 at the 4th, 8th, and 12th weeks were better. The constant expression of type Ⅱ collagen in the experimental group was significantly higher than that in the control group. Conclusions Weekly intra-articular injections of BMP-7 can alleviate the progression of osteoarthritis.