骨形态发生蛋白-7复合纤维蛋白对大鼠骨质疏松性椎体骨折愈合的影响

目的:观察以纤维蛋白为载体的骨形态发生蛋白-7(BMP-7)对骨质疏松性椎体骨折愈合的影响,探讨局部应用BMP-7纤维蛋白复合物治疗骨质疏松性椎体骨折的可行性。方法:雌性SPF级8月龄SD大鼠54只,随机选取36只,经去除卵巢建立骨质疏松模型并随机分为A、B组,每组18只;另18只行伪手术,在背部卵巢周围切除等体积脂肪,作为对照组(C组)。术后3个月所有动物采用L5椎体手术开窗刮除术区内松质骨方法建立骨折模型,A组骨折区内放入含BMP-724μg和纤维蛋白20mg的凝胶状混合物,B组和C组于同部位放入等体积小牛血清,盖好窗口骨瓣。建立骨折模型后4、6、8周,每组处死动物3只,取L5椎体切片行HE染色;6、8、12周时每组处死动物3只,行L5椎体力学性能测试(载荷能力、弹性模量和最大应变量)。结果:骨折后4周3组骨折区均有纤维骨痂形成,但B组纤维骨痂量少于A、C组;6周时A、C组有较多骨性骨痂形成,B组仅有微量骨性骨痂;8周时A、C组均为成熟小梁骨,骨折基本愈合,B组骨性骨痂量少,仍以纤维骨痂为主,尚有部分骨缺损存在;各时间点A组与C组相似。骨折后6、8、12周A、C组L5椎体的最大载荷、弹性模量及8、12周时的最大应变量均明显高于B组(P0.05或0.01),B组6周时的最大应变量与A、C组比较无显著性差异(P0.05),各时间点A组与C组比较无显著性差异(P0.05)。结论:局部应用以纤维蛋白为载体的BMP-7能明显促进大鼠骨质疏松性椎体骨折的愈合,纤维蛋白可作为BMP-7的载体。     

仙灵骨葆胶囊对骨质疏松性骨折大鼠骨生长因子及骨折愈合的影响

目的 探讨仙灵骨葆胶囊对骨质疏松性骨折大鼠骨生长因子BMP-2、IGF-1表达及骨折愈合的影响。方法 48只雌性SD大鼠随机分为：假手术组、模型组、雌二醇组、仙灵骨葆组，12只/组，采用“双侧卵巢切除术+右侧股骨干骨折髓内固定术”构建骨质疏松性骨折大鼠模型，评估骨折愈合情况，检测股骨骨痂BMD、股骨骨生物力学指标和血清骨代谢相关指标，检测骨痂BMP-2、IGF-1蛋白表达。结果 模型组较假手术组骨折愈合评分、股骨痂BMD、股骨骨生物力学指标（最大载荷、最大应力、最大位移）、骨痂BMP-2和IGF-I阳性表达均显著降低（P<0.05），雌二醇组、仙灵骨葆组较模型组骨折愈合评分、股骨痂BMD、股骨骨生物力学指标、骨痂BMP-2和IGF-I阳性表达均显著升高（P<0.05），均以仙灵骨葆组最高。模型组较假手术组血清骨代谢指标（BGP、PICP、TRACP-5b）均显著升高（P<0.05），雌二醇组、仙灵骨葆组较模型组血清骨代谢指标均显著降低（P<0.05），以仙灵骨葆组最低。结论 仙灵骨葆胶囊可能通过介导提高骨质疏松性骨折大鼠骨生长因子BMP-2和IGF-1表达，改善骨代谢，加速骨痂形成，增加骨密度，提高骨生物力学，促进骨折愈合。     

骨形态发生蛋白-7在前列腺癌组织中的表达及意义

目的 研究骨形态发生蛋白-7(BMP-7)在前列腺癌(PCa)组织中的表达及意义.方法 经病理检查确诊PCa组织标本87例.患者平均年龄66(59～78)岁,术前或穿刺前血清总PSA(t-PSA)平均45.7(2.4～138.2)ng/ml.Gleason评分≤6分37例,7分18例,≥8分32例.临床分期:I期(T1a N0 M0)+Ⅱ期(T1b N0M0,T1cN0M0,T2N0M0)20例,Ⅲ期(T3N0M0)20例.Ⅳ期(T4N0M0,TxN1M0,TxN0M1)47例,其中TxN0M1 45例.根据核素骨扫描或正电子发射计算机体层成像CT检查结果分为:PCa无骨转移42例,PCa伴骨转移45例.以30例BPH组织标本为对照,患者平均年龄68(57～88)岁.免疫组织化学PV法检测BMP-7在PCa组织和BPH组织中的表达,统计学分析2组及PCa组内表达差异,PCa组织中BMP-7与血清t-PSA相关性采用Pearson相关性分析. 结果BPH组织中BMP-7表达吸光度A值为70.55±5.41,PCa组织中为70.47±6.18,2者比较差异无统计学意义(P>0.05).PCa无骨转移组BMP-7表达吸光度A值为65.94±1.76,伴有骨转移组为74.80±5.76,2者比较差异有统计学意义(P<0.05).Gleason评分≤6分者吸光度A值为65.96±1.56,7分者为65.83±2.75,≥8分者为78.06±1.39.≤6分和7分者分别与≥8分相比,BMP-7表达A值差异有统计学意义(P<0.05).临床分期编组中Ⅰ期+Ⅱ期BMP-7表达A值为65.86±1.72,Ⅲ期为65.87±1.85,Ⅳ期为74.49±5.83,Ⅰ期+Ⅱ期和Ⅲ期分别与Ⅳ期相比,差异有统计学意义(P<0.05).PCa组织中BMP-7表达A值与血清t-PSA值呈正相关关系(r=0.77,P<0.05).结论 病理Gleason高评分、临床分期、已发生骨转移的PCa组织中高表达BMP-7,BMP-7表达水平与血清t-PSA具有正相关性,提示BMP-7可能是促进PCa细胞发生骨转移的重要细胞因子之一.     

Bone morphogenetic protein-2 coating of titanium implants increases biomechanical strength and accelerates bone remodeling in fracture treatment: a biomechanical and histological study in rats

Bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor (TGF)-beta superfamily, is known to be a very potent osteoinductive growth factor. The purpose of this study was to investigate the effect of BMP-2 (5% [w/w], 50 microg on each nail), locally released from poly(D,L-lactide) (PDLLA)-coated intramedullary implants, on fracture healing. A closed fracture of the right tibia of 5-month-old Sprague-Dawley rats (n = 64) was intramedullary stabilized with uncoated vs. BMP-2-coated titanium Kirschner wires. X-ray examinations (posteroanterior and lateral) were performed throughout the experiment. At 28 and 42 days after fracture, the animals were killed and both tibiae were dissected for biomechanical torsional testing. For histological and histomorphometric evaluation, 5 microm sections were obtained, stained with Safranin-O/light green and von Kossa, and examined using an image analysis system. The radiological results demonstrated progressed callus consolidation in the BMP-2-treated groups compared with the uncoated groups at both timepoints. Histomorphometric evaluation showed progressed callus remodeling with significantly increased mineralization and less cartilage of the periosteal callus. Due to the BMP-2 treatment, increased mineralization of the cortices was detected at 28 and 42 days after fracture. Biomechanical testing revealed significantly elevated maximum load and torsional stiffness in the BMP-2-treated groups compared with controls at both timepoints. The results clearly demonstrate that local application of BMP-2 from PDLLA-coated implants is feasible and significantly accelerates fracture healing. Local administration of growth factors from coated implants could reduce clinical problems in fracture treatment without opening of the fracture, implantation of further devices, or injection with the risk of infection or side effects caused by other carriers.     

Health economics: a cost analysis of treatment of persistent fracture non-unions using bone morphogenetic protein-7

OBJECTIVE: To compare the cost implications of treatment of persistent fracture non-unions before and after application of recombinant human bone morphogenetic protein-7 (BMP-7). METHOD: Of 25 fracture non-unions, 9 were treated using BMP-7 alone and 16 using BMP-7 and bone grafting. These patients were prospectively followed up, and the costs incurred were analysed. RESULTS: The mean number of procedures per fracture performed before application of BMP-7 was 4.16, versus 1.2 thereafter. Mean hospital stay and cost of treatment per fracture before receiving BMP-7 were 26.84 days and pound 13,844.68, versus 7.8 days and pound 7338.4 thereafter. The overall cost of treatment of persistent fracture non-unions with BMP-7 was 47.0% less than that of the numerous previous unsuccessful treatments (p=0.001). CONCLUSIONS: Treating fracture non-unions is costly, but this could be reduced by early BMP-7 administration when a complex or persistent fracture non-union is present or anticipated.     

Local ZnCl2 accelerates fracture healing

This study evaluated the effect of local zinc chloride (ZnCl₂), an insulin mimetic agent, upon the early and late parameters of fracture healing in rats using a standard femur fracture model. Mechanical testing, radiographic scoring, histomorphometry, qualitative histological scoring, PCNA immunohistochemistry, and local growth factor analysis were performed. Fractures treated with local ZnCl₂ possessed significantly increased mechanical properties compared to controls at 4 weeks post fracture. The radiographic scoring analysis showed increased cortical bridging at 4 weeks in the 1.0 (p = 0.0015) and 3.0 (p < 0.0001) mg/kg ZnCl₂ treated groups. Histomorphometry of the fracture callus at day 7 showed 177% increase (p = 0.036) in percent cartilage and 133% increase (p = 0.002) in percent mineralized tissue with local ZnCl₂ treatment compared to controls. Qualitative histological scoring showed a 2.1× higher value at day 7 in the ZnCl₂ treated group compared to control (p = 0.004). Cell proliferation and growth factors, VEGF and IGF‐I, within fracture calluses treated with local ZnCl₂ were increased at day 7. The results suggest local administration of ZnCl₂ increases cell proliferation, causing increased growth factor production which yields improved chondrogenesis and endochondral ossification. Ultimately, these events lead to accelerated fracture healing as early as 4 weeks post fracture. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:834–841, 2014.     

Effect of strontium ranelate on fracture healing in the osteoporotic rats

The aim of this study was to evaluate the effect of strontium ranelate (SrR) on fracture healing in the osteoporotic rat model. Forty female Sprague–Dawley rats aged 3 months were enrolled in the study. Osteoporosis was induced by bilateral ovariectomy and subsequent daily heparin injection started 1 week after surgery and lasted for 4 weeks. Osteoporosis was confirmed by a reduction of bone mineral density (BMD). Twenty of the osteoporotic rats were assigned to the SrR group and the remaining 20 to the control group. An open right tibial midshaft transverse fracture was created and then an intramedullary fixation was performed. SrR group was treated by 450 mg/kg/day SrR per oral. Six weeks after surgical induction of fracture, all animals were sacrificed. One animal from each group died after ovariectomy. Two tibiae from the control group failed to unite. SrR‐treated group showed higher mechanical strength and fracture stiffness when compared to the control group (p = 0.006, p = 0.001, respectively). SrR‐treated group had mature woven bone or predominantly woven bone compared with osteoporotic control group (p = 0.038). SrR‐treated group's callus maturity was significantly higher than control group (p = 0.001). SrR is associated with better fracture healing in the osteoporotic rat model. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:138–142, 2011     

Bone morphogenetic proteins in orthopaedic surgery

Bone morphogenetic proteins (BMPs) are growth factors which induce new bone formation. They are an increasingly important adjunct in the treatment of certain musculoskeletal disorders. Their underlying basic science and role in bone healing is explained. Delivery systems, safety issues and current evidence-based clinical applications of BMPs in orthopaedic surgery are described.     

BMP-7 stimulates early diaphyseal fracture healing in estrogen deficient rats

Estrogen deficiency causes postmenopausal osteoporosis. The relationship between estrogen deficiency and the high failure rate after osteoporotic fracture treatment is unclear, as is the effect of possible interventions, either with anti-resorptive agents or with anabolic agents such as bone morphogenetic proteins (BMPs). To investigate the influence of estrogen deficiency as well as the effect of early intervention, forty female wistar rats underwent ovarectomy (OVX) followed by low calcium diet. Ten rats underwent sham operations, followed by normal diet. After 6 weeks, a closed midshaft femoral fracture was induced. Ten animals received a systemic bisphosphonate injection, 10 injection of BMP-7 in the fracture, and 10 a combination. All then received a normal diet. After 2 weeks healing was evaluated using radiographs, CT, biomechanical testing, and histology. Radiography showed significant increase of bridging in groups treated with BMP-7. Callus volume was higher in these groups. Bending stiffness and strength were similar between OVX and sham, and not influenced by bisphosphonates. Significant increase was seen in groups treated with BMP-7. Histology was in accordance with other endpoints. Early fracture healing was not affected by estrogen deficiency. While no beneficiary effect of bisphosphonate treatment was found, injection of BMP-7 stimulated healing in ovarectomized rats.     

急性和亚急性骨质疏松椎体骨折不同愈合时期骨组织形态学分析

目的 观察急性和亚急性骨质疏松性椎体压缩骨折（osteoporotic vertebral compression fracture,OVCF）发生后,不同愈合时期椎体内骨组织病理特点。方法 将119例（OVCF）患者按发病时间分为四期：I期(0~15 d);II期(15~30 d);III期(30~60 d);IV期(60~90 d)。常规行椎体内骨折区活检骨组织取出,制备脱钙活检标本,运用光镜观察并骨组织形态计量学分析。结果 共获得活检标本119例,其中I期67例(56.3 %)、II期28例(23.5 %)、III期12例(10.8 %)、IV期13例(10.9 %)。所有病理标本均未发现肿瘤或结核。骨折时间与骨组织形态学改变呈显著正相关,镜下表现为骨折区域的修复变化：从早期血肿和炎性浸润到肉芽期织和纤维组织的增生,进一步软骨成骨、钙盐沉积,最终形成新的编织骨。骨组织形态学测量结果显示I期、II期FV/TV(%)显著增高(P<0.0001,r=0.4882),III期OS/BS(%)显著增高(P<0.0001,r= -0.5727),IV期WBV/TV(%)显著增高(P<0.0001,r= -0.5836)。结论 骨折时间是骨折愈合分期重要的预测因素,发病时间不同,其椎体内部的病理变化也不尽相同。     

输尿管逆向注射重组腺病毒介导的BMP-7对大鼠肾间质纤维化的作用

目的：构建出具有转染后能表达活性的骨形成蛋白-7（BMP-7）的重组腺病毒,将其直接导入肾纤维化大鼠肾脏,观察其抗肾纤维化的作用。方法：无菌级雄性SD大鼠48只随机分为假手术组、单侧输尿管梗阻（UUO组）组、BMP-7治疗组,以免疫组织化学方法检测肾组织中α-SMA蛋白的表达水平,以逆转录-多聚酶链反应技术检测TGF-β1的表达水平。结果：免疫组化结果示：BMP-7组肾小管间质α-SMA表达显著减少（P〈0.05）。RT-PCR结果显示：TGF-β1随梗阻时间延长而逐渐增多,第28天,有所下降,但无统计学意义。在治疗组,BMP-7组比同一识相点UUO组TGF-β1表达减少（P〈0.05）。结论：BMP-7能够明显减轻肾间质纤维化,下调TGF-β1的表达,从而发挥其在单侧输尿管结扎模型中对肾脏的保护作用,延缓和抑制了肾间质纤维化的发展。     

利塞膦酸钠对大鼠骨质疏松性非典型性骨折愈合的影响

目的 探讨利塞膦酸钠对大鼠骨质疏松性非典型性骨折愈合的影响。方法 选取健康6月龄SD雌性大鼠60只,随机分为正常对照组（A组）、去卵巢模型+股骨干骨折模型+利塞膦酸钠灌胃治疗组（B组）、去卵巢模型+股骨干骨折模型+生理盐水灌胃组(C组), 每组20只。骨折模型建模后第3周和第6周时动态观察股骨骨密度(bone mineral density,BMD)、骨矿物质含量(bone mineral content,BMC)、影像学及骨组织显微形态学的改变。结果 ①通过X线检查结果可知,B组在第3、第6周时,骨折处骨痂形成,局部骨密度越来越高,前3周骨折出现愈合加速,后3周出现明显延迟愈合情况;同时期B组、C组骨折处相比较,前3周B组大鼠出现骨折处骨连续性较A组、C组好,但在第6周时,B组大鼠出现骨折处骨连续性较A组、C组差,骨折处局部出现骨折延迟愈合情况;②同时期各组大鼠病理切片结果对比,B组大鼠在前3周骨折处增殖的软骨细胞较A组、C组多,骨小梁较密集,骨小梁相互之间连接性较好,骨皮质厚度更大,骨折愈合情况更好;但在后3周时,B组大鼠较A组、C组骨折处增殖的软骨细胞少,骨小梁稀疏,骨小梁相互之间连接性差,骨皮质厚度变化不明显,出现骨折愈合延迟现象;在同时期前后对比中,B组大鼠在前3周局部骨折处出现明显加速现象,后3周则出现明显延迟愈合现象;③各组大鼠BMD、BMC组间、组内对比中,结果具有统计学意义,说明利塞膦酸钠在前3周可显著提高大鼠骨折处BMD、降低大鼠骨折处BMC,且显著提高骨折处BMD增加速度,延缓骨折处BMC降低速度,但在后3周出现延迟骨折愈合情况。结论 早期骨质疏松性非典型性骨折患者愈合过程中建议使用利塞膦酸钠,中、后期则不建议使用。     

Recombinant human bone morphogenetic protein‐7 enhances fracture healing in an ischemic environment

Ischemia predisposes orthopedic trauma patients to delayed fracture healing or nonunion. The goal of this study was to test the ability of bone morphogenetic protein 7 (BMP7) to stimulate fracture repair in an ischemic environment. Ischemic fractures were generated in male adult mice by resecting the femoral artery prior to the creation of a nonstabilized tibia fracture. Recombinant human BMP7 (rhBMP7, 50 µg) was injected into the fracture site immediately after surgery. At 7 days after injury, more tissue vascularization was observed in rhBMP7 treated fractures. Histomorphometric analyses revealed that rhBMP7 induced more cartilage at day 7, more callus and bone at days 14 and 28, and more adipose tissue and fibrous tissue at days 7, 14, and 28 compared to controls (n = 5/group/time). At day 28, all fractures treated with rhBMP7 (50 µg, n = 5) healed, whereas only three of five control fractures exhibited slight bony bridging. In addition, we found that rhBMP7 (both 10 and 50 µg) significantly increased the amount of cartilage compared to controls in stabilized fractures, confirming its chondrogenic effect. Lastly, using bone marrow transplantation, we determined that no donor‐derived osteocytes or chondrocytes were present in rhBMP7‐treated fractures, suggesting rhBMP7 did not recruit mesenchymal stem cells from the bone marrow to the fracture site. In conclusion, our results indicate that rhBMP7 is a promising treatment for fractures with severely disrupted blood supply. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:687–696, 2010     

局部应用CPC/rhBMP-2复合材料对骨质疏松大鼠骨折愈合的影响

目的研究磷酸钙骨水泥（Calcium Phosphate Cement，CPC）与重组人骨形态发生蛋白-2（Recombinant Human Bone Morphogenefic Protein-2，rhBMP-2）复合材料对骨质疏松大鼠骨折愈合的影响。方法取4月龄雌性清洁大鼠106只，随机分成实验组96只，对照组10只。实验组行双侧卵巢切除术，对照组行假手术，术后行双能X线骨扫描确定骨质疏松动物模型形成。然后将实验组96只大鼠制作右侧股骨远端松质骨骨折，将上述动物随机分成3组，每组32只：（1）克氏针组，从髁间窝穿入直径1mm克氏针固定；（2）CPC组，将CPC从12号针头注入骨髓腔，手法固定至骨水泥凝固；（3）CPC-BMP组，将CPC与rhBMP-2复合材料用12号针头注入骨髓腔，手法固定至骨水泥凝固。术后第2、4、6、8wk三组各取8只动物处死，取手术侧股骨远端标本行压缩实验。结果在上述4个时间点，CPC-BMP组的骨折段最大载荷较克氏针组及CPC组增高（P〈0．05）；第2周CPC组骨折段最大载荷较克氏针组增高（P〈0．05）。结论（1）局部注射CPC-BMP复合材料可以促进骨质疏松大鼠骨折的愈合，提高骨折愈合后的强度；（2）CPC局部应用可以对骨折起到即时固定作用。     

降钙素对卵巢切除大鼠股骨骨折愈合的影响

目的观察降钙素对卵巢切除大鼠股骨骨折愈合的作用，为临床上治疗骨质疏松性骨折提供实验依据。方法50只雌性、14周龄SD大鼠共分成5组，每组10只。分成假手术组（Sham，G1），双侧卵巢切除术组（OVX，G2），假手术＋骨折组（Sham＋F，G3），卵巢切除术＋骨折组（OVX＋F，G4），卵巢切除＋骨折＋降钙素药物组（OVX＋F＋CT，G5），骨折组大鼠均采用右股骨中段横行骨折，髓内针固定；降钙素采用皮下给药，隔日1次（16IU·kg^-1）。所有大鼠于术后4周杀死，取右侧股骨标本。然后，分别进行CR摄片、组织形态学观察，并应用双能X线骨密度仪（DEXA）测量右股骨整体、远段和中段骨密度以及BMP-2免疫组化观察，并应用病理图像分析仪对BMP-2免疫组化进行光密度测量。结果（1）OVX组与Sham组比较，BMD显著下降。（2）OVX＋F＋CT组与OVX＋F组比较：骨痂mBMD显著增高；BMP-2的表达无显著性差异。结论降钙素对OVX大鼠股骨骨折具有明显促进骨折愈合的作用，加速编织骨向板层骨的演变过程。     

鲑鱼降钙素联合恒古骨伤愈合剂治疗腰椎OPF疗效分析

目的 探讨鲑鱼降钙素联合恒古骨伤愈合剂治疗腰椎骨质疏松性骨折(OPF)的疗效.方法 自2007年11月至2009年12月简阳市人民医院骨科共收治82例腰椎骨质疏松性骨折,随机分成治疗组和对照组,治疗组42例给予鲑鱼降钙素和恒古骨伤愈合剂联合治疗,对照组40例仅给予鲑鱼降钙素治疗,比较2组的疼痛缓解效果.结果 82例治疗前用视觉模拟评分法(VAS)评分为6～9分,2组间的疼痛评分差异无统计学意义(P>0.05).治疗后3、5、8、15 d,2组疼痛VAS评分分别经秩和检验差异有统计学意义(P<0.01).治疗组不但疼痛缓解快,3个月后复查骨矿物密度改善程度亦明显优于对照组.结论 鲑鱼降钙素联合恒古骨伤愈合剂治疗腰椎骨质疏松性骨折具有良好止痛和促进成骨作用,是一种安全、有效的方法.     

Local manganese chloride treatment accelerates fracture healing in a rat model

This study investigated the effects of local delivery of manganese chloride (MnCl₂), an insulin‐mimetic compound, upon fracture healing using a rat femoral fracture model. Mechanical testing, histomorphometry, and immunohistochemistry were performed to assess early and late parameters of fracture healing. At 4 weeks post‐fracture, maximum torque to failure was 70% higher (P < 0.05) and maximum torsional rigidity increased 133% (P < 0.05) in animals treated with 0.125 mg/kg MnCl₂ compared to saline controls. Histological analysis of the fracture callus revealed percent new mineralized tissue was 17% higher (P < 0.05) at day 10. Immunohistochemical analysis of the 0.125 mg/kg MnCl₂ treated group, compared to saline controls, showed a 379% increase in the density of VEGF‐C+ cells. In addition, compared to saline controls, the 0.125 mg/kg MnCl₂ treated group showed a 233% and 150% increase in blood vessel density in the subperiosteal region at day 10 post‐fracture as assessed by detection of PECAM and smooth muscle α actin, respectively. The results suggest that local MnCl₂ treatment accelerates fracture healing by increasing mechanical parameters via a potential mechanism of amplified early angiogenesis leading to increased osteogenesis. Therefore, local administration of MnCl₂ is a potential therapeutic adjunct for fracture healing. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:122–130, 2015.     

负载重组人骨形态发生蛋白-2的超高相对分子质量聚-DL-乳酸接骨板修复骨折的研究

目的利用可吸收超高相对分子质量聚-DL-乳酸（PDLLA）接骨板作为缓释重组人骨形态发生蛋白-2（rhBMP-2）的载体，通过体内活性实验来评估其固定骨折及修复缺损的效果。方法新西兰大白兔32只，制成双侧尺骨中段2．5mm骨及骨膜缺损模型，右侧为实验组，左侧为对照组，实验组采用复合rhBMP-2的PDLLA接骨板固定，对照组采用普通PDLLA接骨板固定。随机分为四组，每组8只，分别于术后2、4、8、12周行大体观察、X线片、组织病理切片观察及计算机图像分析观察，比较两种不同方法在不同时段对骨折与缺损的修复情况，以及固定效果与体内降解情况。结果术后2、4、8、12周行大体观察及X线片检查示两种生物活性接骨板均固定牢固，骨折端无移位，对位、对线良好。结合组织病理切片观察，术后8周，7只动物实验侧骨折及缺损区获得骨折修复，2只动物对照侧存在较少量骨痂相连，其余动物骨缺损主要由纤维结缔组织填充；术后12周，8只动物两种不同方法固定的骨折及缺损区均获得修复，但实验组固定板材与周围组织的相容性、成骨速度、骨再生量、再生髓腔结构等方面均优于对照组，计算机图像分析结果显示同时期内实验组骨小梁的生成数量和质量均显著优于对照组（P〈0．01）。结论复合rhBMP-2的可吸收PDLLA接骨板生物相容性好，对X线等成像检查无干扰，并具有良好骨诱导性和骨缺损修复能力，无需二次手术取出。     

骨形态发生蛋白-7在幼年大鼠肾小管间质损伤中的表达及意义

目的：探讨单侧输尿管梗阻（UUO）幼年大鼠肾间质纤维化形成过程中骨形态发生蛋白-7（BMP-7）的表达趋势及其与转化生长因子-β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）的相关关系;观察血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体拮抗剂（ARB）的干预作用。方法：采用单侧输尿管结扎制备UUO模型。3～4周龄幼年Wistar雄性大鼠随机分为对照组、模型组和干预组。于实验第3、7、14、28天取大鼠8只处死。HE及Masson染色观察肾组织的病理改变;免疫组化半定量检测各组大鼠肾组织BMP-7、TGF-β1及α-SMA蛋白表达。了解BMP-7与TGF-β1、α-SMA、肾间质纤维化程度的关系。结果：随梗阻时间延长,模型组BMP-7表达逐渐下降,TGF-β1、α-SMA表达进行性增高,干预组BMP-7表达较模型组显著增加（P〈0.05）;TGF-β1、α-SMA表达较模型组明显减少（P〈0.05）。模型组肾小管间质TGF-β1、α-SMA表达明显增高（P〈0.05）,BMP-7表达显著减少（P〈0.05）。与模型组相比,干预组肾小管间质TGF-β1、α-SMA表达显著减少（P〈0.05）,而BMP-7表达显著增多（P〈0.05）。BMP-7与TGF-β1、α-SMA、肾间质纤维化程度成负相关（r分别为-0.844、-0.787、-0.952,P均〈0.01）。结论：BMP-7表达减少伴随着肾小管上皮细胞转分化出现,提示BMP-7可能具有维持小管上皮细胞表型作用。苯那普利联合氯沙坦可能通过下调TGF-β1、α-SMA蛋白的异常高表达,上调BMP-7蛋白的异常低表达,直接或间接负性调控肾小管上皮细胞转分化,阻止肾间质纤维化进展。     

骨质疏松性骨折愈合过程中的骨重建因子

一般性骨折愈合过程分为血肿机化演进期、原始骨痂形成期和骨痂改造塑形期;而骨质疏松性骨折愈合过程分为纤维骨痂期、软骨骨痂期和骨性骨痂期。骨质疏松性骨折愈合的组织学观察表明,纤维骨痂期主要是成纤维细胞合成Ⅲ型胶原;软骨骨痂期主要是成软骨细胞合成、分泌Ⅱ型胶原;骨性骨痂期主要是随着软骨内成骨的出现和发展,Ⅱ型胶原消失,逐渐由抗张力性能较强的Ⅰ型胶原所取代。一般来说,实验性骨质疏松性骨折的愈合方式与一般性骨折愈合方式相似,软骨内成骨和膜内成骨共同参与了骨质疏松性骨折的修复过程,但以软骨内成骨为主。