大鼠内侧半月板切除后髌骨的组织学变化及疼痛发生的机制  

Analysis of Histological Change of Patella from Meniscectomized Rats and Study of Mechanism of Pain

作　　者：任建华[1] 金文涛[1] 朱蕾[2] 张荣凯[3] 曾春[1] 王昆[1] 

机构地区：[1]中山大学附属第三医院骨科,广东广州510630 [2]中山大学附属第三医院整形外科,广东广州510630 [3]中山大学附属第五医院骨科一区,广东珠海519000

出　　处：《中山大学学报（医学科学版）》2011年第3期303-310,共8页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东自然科学基金(8151008901000049)

摘　　要：【目的】分析大鼠内侧半月板切除后髌骨的组织学改变,并探讨髌骨疼痛产生的机制。【方法】大鼠分为实验(MMx)组(n=30),假手术(Sham)组(n=30)和对照(Control)组(n=30)。实验组切除右膝内侧半月板及内侧副韧带,Sham组仅暴露半月板,Control组未予手术。术前1d及术后第1、2、4、7、14、21及28天测量各组大鼠右后肢机械刺激撤足阈值。术后第1、2和4周各组分别杀死10只大鼠,取右侧髌骨,分析其大体改变以及软骨和软骨下骨的组织病理学变化,并测量软骨下骨增生的血管。同时,应用免疫组化技术检测髌骨中血管内皮生长因子(VEGF)、神经生长因子(NGF)、P物质和肿瘤坏死因子α(TNF)的表达和分布。【结果】①术后MMx组右后肢的机械刺激疼痛阈值显著下降并维持在较低水平至实验结束,且显著低于Sham组和Control组。术后1周内Sham组右后肢痛阈下降但2周左右恢复到术前水平;实验过程中Control组痛阈无变化。②术后第1周开始MMx组髌软骨发生退变,且随时间而不断加重,Mankin's评分也逐渐增加。术后第2周MMx组软骨下骨出现重塑,第4周更加显著:软骨下骨增生的血管突破潮线侵蚀深层软骨,呈多重潮线和潮线中断,软骨下骨平均厚度显著下降。Sham组与Control组各时间点髌软骨及软骨下骨无显著退变,Mankin's评分无明显变化改变。③免疫组化显示MMx组术后髌软骨中VEDF和NGF的表达较Sham组和Control组显著增强,且随时间逐渐增强。MMx组术后髌骨中TNF-α和P物质的表达显著增强,且主要分布于增生的血管壁周围基质和软骨细胞中。Sham组和Control组上述各因子表达微弱。【结论】①内侧半月板及内侧副韧带切除后髌骨有逐渐加重的骨关节炎改变,患肢有骨关节炎疼痛反应;②软骨内上调的VEDF和NGF与软骨退变、软骨下骨重塑及血管增生相关;③软骨下骨增生的血管及其周围上调的疼痛相关分子可�[Objective] To analyze histological change at patella from meniscectomized rats and subsequently to study the mechanism of pain from patella.[Methods] Rats were divided into 3 groups：operation（MMx）group（n=30）,sham-operation（Sham） group（n=30）,and normal（Control） group（n=30）.Medial meniscus and medial collateral ligament（MCL） of right knee was resected in MMx group while reserved after being exposed in Sham group.No surgery in Control group.Then mechanical thresholds of pain were tested and histological change of cartilage and subchondral bone at patella were evaluated on 1,2,and 4 weeks post-operation.Angiogenesis at the subchondral bone was measured and molecules such as tumor necrosis factor-α（TNF-α）,vascular endothelial growth factor（VEDF）,nerve growth factor（NGF）,substance P were detected by immunohistochemistry.[Results]（1） The pain thresholds in MMx group declined dramatically after surgery and remained at lower level than that in Sham and Control group.（2） The patella cartilage degenerated more in MMx group in accordance with Mankin＇s score of cartilage after surgery.Subchondral bone remolding occurred 2 weeks post surgery and significant change appeared 4 weeks later：blood vessels crossing the osteochondral junction,breaching tidemarks and eroded deep cartilage.The tidemarks doubled and disappeared.The thickness of subchondral bone decreased.The cartilage and subchondral bone appeared normally in Sham and Control group.（3）VEDF and NGF were identified at cartilage and TNF-α and substance P were expressed excessively around neo-vascularization at osteochondral junction in MMx group.All cytokines were detected weakly in Sham and Control group.[Conclusions],（1）The patella from rats with MCL and medial meniscus resection presents change of osteoarthritis（OA）and the model imitate OA pain of knee joint;（2）Up-regulation of VEDF and NGF correlate with the degeneration of cartilage,remolding of subchondral bone and angiogenesis;（3）Neo-vascu

关 键 词：髌骨 疼痛 肿瘤坏死因子α 血管内皮生长因子 神经生长因子 P物质 

分 类 号：R363[医药卫生—病理学]