降钙素基因相关肽对大鼠胫骨骨折早期愈合的影响  

Effects of calcitonin gene-related peptide on tibial fracture healing at early stage in rats

作　　者：韩娜[1] 张殿英[1] 王天兵[1] 张培训[1] 姜保国[1] 

机构地区：[1]北京大学人民医院创伤骨科,北京100044

出　　处：《第三军医大学学报》2008年第21期2011-2014,共4页Journal of Third Military Medical University

基　　金："十一五"国家科技支撑计划(2007BA104B00);国家重点基础研究发展计划(973计划)(2003CB515306)~~

摘　　要：目的建立大鼠单纯胫骨骨折模型,分别给予大鼠腹腔注射不同浓度的外源性降钙素基因相关肽(calcitonin gene-related peptide,CGRP)及其特异性受体拮抗剂,评价并探讨CGRP对骨折早期愈合的影响及其对骨形成蛋白-2(bone morphogenetic protein-2,BMP-2)的表达。方法制作单纯胫骨骨折模型,将SD大鼠应用随机数字表法随机分为3组,每组10只,分别给予腹腔注射生理盐水(对照组)、CGRP及CGRP受体拮抗剂。术后1、2周和4周时取材,进行骨折部骨痂测量,HE染色观察骨折局部形态变化;利用免疫组织化学检测骨组织中BMP-2的表达情况。结果大鼠腹腔内注射CGRP1周时,各组均可见到少许骨痂,组间未见明显差别;术后2周时,各组外观有差别,CGRP组大鼠胫骨骨折部呈膨大样,大鼠骨痂量多于盐水对照组和拮抗剂组;术后4周CGRP组骨折部膨大明显缩小,骨皮质连续性好,各组外形已接近正常胫骨形态及大小。免疫组织化学结果显示:CGRP组胫骨骨折大鼠在骨折断端附近BMP-2的表达信号强于对照组和拮抗剂组。用药1周时,BMP-2免疫活性细胞从对照组的(18.52±10.08)增加为(36.80±11.18),增加了近2.2倍,拮抗剂组则减少为(14.50±8.80);用药2周时,BMP-2免疫活性细胞从对照组的(20.26±6.78)增加为(52.18±10.42),拮抗剂组减少为(11.21±8.40),变化幅度最大;用药4周时,BMP-2免疫活性细胞的增加从对照组的(21.25±8.65)增加为(31.41±9.18),拮抗剂组则减少为(18.32±10.28)。结论CGRP可能具有促进大鼠胫骨骨折早期愈合的作用,CGRP可以诱导骨组织中BMP-2的表达,推测CGRP的成骨作用与BMP-2的表达具有相关性。Objective To investigate the effect of calcitonin gene-related peptide （CGRP） on early-stage bone fracture healing and on the expression of bone morphogenetic protein-2 （ BMP-2 ） in bone tissue of rats. Methods Totally 30 SD rats with tibial fracture were randomly and equally divided into 3 group and received normal saline （control group）, CGRP or CGRP receptor antagonist injection intraperitoneally. In 1, 2 and 4 weeks later, the fracture sites from the 3 groups were subjected to X-ray scanning, callus measurement and HE staining. The expression of the BMP-2 was detected by immunohistochemical method. Results There was no obvious difference on callus amounts among the 3 groups, but at 2 weeks after treatment, there were significantly more callus in CGRP group with enlargement in the fracture site than in the other 2 groups ; The enlargement of CGRP group became minimized with fused cortex and almost normal morphology and size. So were the other 2 groups, hnmunohistochemical results showed that exogenous CGRP significantly increased BMP-2 expression, but the expression was decreased significantly after administration of CGRP receptor antagonist. Conclusion Our results suggest that CGRP may participate in the regulation of bone fracture healing, and induce BMP-2 production, implying that BMP-2 may be related functionally with CGRP in the mechanism of bone metabolism.

关 键 词：降钙素基因相关肽 大鼠 骨折 BMP-2 

分 类 号：R-332[医药卫生] R341