细胞周期蛋白依赖性激酶9（CDK9）在腰椎后路术后多裂肌损伤性萎缩中的作用和机制

项目名称： 细胞周期蛋白依赖性激酶9（CDK9）在腰椎后路术后多裂肌损伤性萎缩中的作用和机制

项目编号： No.81472064

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 范顺武

作者单位： 浙江大学

项目金额： 72万元

中文摘要： 腰椎后路术后多裂肌损伤性萎缩是顽固性腰背痛的重要原因，临床通过微创技术进行预防，取得了一定疗效，但并不能完全防治其发生发展。国外研究表明骨骼肌损伤后 24h内是中性粒细胞浸润、破坏肌纤维的主要时期；我们观察到术后3h多裂肌损伤轻微，但随着中性粒细胞的浸润，肌损伤逐渐加剧、扩散，术后24h中性粒细胞浸润程度与多裂肌早期损伤和远期萎缩程度密切相关。体外研究发现细胞周期蛋白依赖性激酶9（CDK9）是中性粒细胞凋亡的重要调控因子，但其确切分子机制尚不明了。骨骼肌损伤后第2天，巨噬细胞开始浸润，激活肌卫星细胞，启动肌再生。研究也表明高表达CDK9能明显促进肌卫星细胞分化成熟，促进肌再生，但其确切分子机制也不明确。因此本项目拟通过体内手术模型，分析CDK9在多裂肌损伤和肌再生中的作用；通过体外细胞培养，探讨CDK9调控中性粒细胞凋亡和肌卫星细胞分化成熟的机制；最终为多裂肌损伤性萎缩的治疗提供分子靶标。

中文关键词： 细胞周期蛋白依赖性激酶9；腰椎；多裂肌；损伤；萎缩

英文摘要： Traumatic atrophy of multifidus muscle after posterior lumbar surgery is the important reason of refractory low back pain. Although clinical studies have reported that minimally invasive techniques can reduce this traumatic atrophy of multifidus, they still can't totally avoid it. Previous studies have shown ~24 h post skeletal muscle injury is the major period of neutrophil infiltration and destroying the muscle fibers. In our own animal study, we found slight injury changes in multifidus muscle at 3 h after posterior lumbar surgery, but as more and more neutrophil infiltrating, the injury changes became severe and spread throughout the specimen, and the degree of neutrophil infiltration 24 h postoperatively was signigicantly associated with the degree of muscle injury at the early stage and the degree of muscle atrophy for long-term follow-up. And latest researches in vitro found that cyclin-dependent kinase 9 (CDK9) is the important regulatory factor of neutrophil apoptosis, however the exact molecular mechanisms have not been studied. From 2nd day post muscle injury, the macrophages began to infiltrate, coincide with the activation and recruitment of muscle progenitor cells to the wound site, and muscle regeneration started. Researches showed that the high expression of CDK9 can significantly promote muscle satellite cell differentiation and maturation, and increase muscle fiber regeneration, however the exact molecular mechanisms are also not clear. So, this project will analyze the effect of CDK9 in the multifidus muscle injury and atrophy, using a rat model in vivo, and the mechanisms of CDK9 on neutrophil apoptosis and muscle satellite cell differentiation and maturation, by cell cultrue in vitro. The object is to provide a theoretical basis for developing new treatments of postoperative multifidus traumatic atrophy.

英文关键词： cyclin-dependent kinase 9;lumbar spine;multifidus muscle;injury;atrophy