辛伐他汀与骨粉复合物填充大鼠胫骨骨缺损修复作用的实验研究

目的研究辛伐他汀作为激活物对大鼠胫骨骨缺损修复的促进作用。方法实验组用辛伐他汀与Bio-Oss骨粉复合物填入大鼠胫骨骨缺损模型,对照组骨缺损单纯填入Bio-Oss骨粉,空白组骨缺损部位不放入骨粉。术后4、8、12周分别处死大鼠,定性、定量分析,观测骨增量变化和骨缺损修复进程。结果空白组无法正常愈合;实验组在新骨生成和改建速度上明显好于对照组。结论辛伐他汀有促进新骨生成作用,加速了骨缺损修复进程。     

辛伐他汀骨粉复合物对骨质疏松大鼠骨缺损的作用

目的 探讨辛伐他汀(simvastatin,Simv)骨粉复合物对骨质疏松大鼠骨缺损愈合的影响.方法 36只雌性SD大鼠去势建立骨质疏松模型,随后在大鼠右侧胫骨建立3 mm骨缺损模型,随机分成3组:A组为空白对照,B组填充单纯骨粉,C组填充2.5% Simv复合骨粉.术后观察骨缺损区局部反应,术后4、 8、 12周对缺损区分别进行Villanueva Bone Stain染色,显微观察;不脱钙骨磨片,荧光显微观察及骨形态计量学分析;X线定性分析缺损部位密度.结果 所有大鼠局部创面愈合正常,无破溃及排斥反应. 4周时,A组1只大鼠缺损处不完全骨折,C组较B组纤维组织少,成骨细胞增多,类骨质形成明显. 8周时,C组骨粉边缘见明显较宽的荧光带,骨小梁和类编织骨结构形成,与B组相比,除类骨质周长百分数外,其余骨形态计量分析指标均显著提高,差异有统计学意义. 12周时,X线显示C组骨密度比B组增高,骨缺损边界基本消失,缺损部位成均匀团状密度增高影;A组缺损未完全愈合.结论 局部填充人工骨粉与Simv复合物对骨质疏松大鼠的胫骨缺损愈合有促进作用.     

辛伐他汀复合骨粉在大鼠颞骨表面成骨作用的实验研究

目的 研究辛伐他汀作为激活物对骨生成的促进作用.方法 72只大鼠随机分为3组.实验组大鼠左侧颞骨骨膜下袋内放置辛伐他汀与Bio-Oss骨粉复合物,对照组单纯填入Bio-Oss骨粉.观察大鼠术区情况和生活状态,于术后4、 8、 12周分别处死大鼠,进行组织学观察、新骨总面积测量、成骨细胞计数和红外光谱分析,观察骨增量变化.结果 空白组4、 8、12周颞骨厚度均无明显变化. 4周,骨粉或复合物相对稳定,未见骨痂生长. 8、 12周,实验组与对照组对比明显.新骨面积和成骨细胞数目实验组多于对照组,实验组新骨生长活跃且速度较快;红外光谱分析,骨痂内无机成分高于对照组.结论 辛伐他汀在大鼠颞骨表面植骨过程中,有促进新骨生成作用.     

辛伐他汀4种给药方法影响大鼠骨缺损愈合的实验研究

目的探讨辛伐他汀的4种给药方式对骨缺损愈合的影响。方法在40只SD大鼠胫骨上建立3mm的骨缺损模型，械侧缺损部位不作处理设为空白对照组、右侧分别给予单纯骨粉修复（A组）、单纯骨粉修复加局部注射辛伐他汀（B组）、局部骨粉复合2.5％辛伐池汀（C组）和骨粉复合15.0％辛伐他汀（D组）修复。术后第4周、8周分别处死各组大鼠，观察骨缺损区成骨情况，结果C组局部愈合正常，无破溃及组织反应，缺损处骨量和骨密度增加明显（比A组高32％．P〈0.05），镜下成骨细胞多，纤维组织最少，整体愈合效果最佳；而B组和D组局部都有破溃及类排斥反应性奶酪状分泌物，缺损局部骨量及骨密度与A组相比没有明显增加（P〉0.05）．炎性细胞及纤维组织较多．个别大鼠局部发生骨折。A组骨密度较空白组高，未见局部有破溃和组织反应，缺损侧胫骨未见完全骨折。而空白组缺损未完全骨性愈合．局部皮肤无破溃及类排除反应．部分大鼠局部发生骨折，结论骨粉复合一定浓度的辛代他汀对正常大鼠的胫骨缺损愈合有促进作用。     

rhBMP-2与人工骨粉复合物对大鼠胫骨骨缺损12周时修复作用的研究

目的：研究重组人骨形成蛋白-2（rhBMP-2）作为激活物促进骨缺损修复的进程。方法：72只大鼠采用左侧胫骨3mm长的骨块缺损模型，随机分为3组，空白组、对照组（填入人工骨粉），实验组（填入100μg／ml浓度的rhBMP-2与人工骨粉复合物）。观察大鼠术区情况和生活状态，于术后4、8、12周分别处死大鼠，进行组织学检测和红外光谱分析。结果：空白组无法正常愈合；实验组的骨量形成和新骨改建速度明显高于对照组。结论：rhBMP-2对骨生成有促进作用，复合材料加速了骨缺损修复的进程。     

骨缺损修复的研究及进展

由于先天性畸形、外伤、肿瘤及失牙后废用性萎缩等原因，需要进行不同程度的骨缺损修复或骨增量治疗，尤其是当前随着牙种植技术的应用和普及，对各种骨修复及骨增量技术发展提出了更紧迫的要求。目前这方面的研究涉及简单的骨块移植、各种骨代用品的运用、骨引导再生技术以及微观领域的细胞因子、转基因工程等多方面。但总的来说，     

HIF-1在骨缺损修复中的作用

骨缺损时,缺损端及其附近的骨膜和血管受损,因此缺损区血管生长能力差,促进细胞增殖及成骨分化所需的营养因子缺乏。而充足的血供是维系骨缺损修复重建的必要条件,因此只有尽早地在骨缺损区构建有效的血管网络,才能为各种细胞的成骨活动提供营养支持和代谢保证。     

载辛伐他汀PLGA/CPC支架材料复合BMSCs修复大鼠颅骨缺损的实验研究

目的:探讨载辛伐他汀PLGA/CPC支架材料复合骨髓间充质干细胞(BMSCs)构建组织工程骨,修复大鼠颅骨临界尺寸骨缺损的可行性以及效果。方法:24只雄性大鼠随机均分为3组;在大鼠颅骨人字缝两侧各做一直径5 mm的骨缺损。每组16个骨缺损再随机分为:载辛伐他汀PLGA/CPC/BMSCs(Brdu标记的BMSCs)组(n=4);载辛伐他汀PLGA/CPC组(n=4);单纯PLGA/CPC组(n=4)以及空白对照组(n=4)。术后4、8、12周取标本分别进行大体观察,HE染色及免疫组织化学染色来评价骨再生情况。结果:术后4、8、12周组织学观察表明载辛伐他汀PLGA/CPC/BMSCs组的成骨质量和速度明显优于其他3组,免疫组化结果显示载辛伐他汀PLGA/CPC/BMSCs组骨钙素(OC)阳性表达IOD值明显高于其他3组。结论:载辛伐他汀PLGA/CPC支架材料复合BMSCs可以诱导大鼠颅骨临界尺寸骨缺损内的新骨形成,成骨质量优于其他3组,而且可以明显缩短骨愈合时间。     

载辛伐他汀PCL-Gt/PCL屏障膜对兔颅骨缺损修复作用的研究

目的　采用同轴静电纺丝技术制备载有辛伐他汀的PCL-Gt/PCL膜修复兔颅骨缺损,观察PCL-Gt/PCL-辛伐他汀膜修复兔骨缺损的作用。方法：制备PCL-Gt/PCL-辛伐他汀膜,扫描电镜观察表面形态,检测辛伐他汀缓释量。选取18只雄性新西兰大白兔随机分为3组,每组6只,制备兔颅骨临界骨缺损模型。空白组缺损区不放置生物膜,阴性对照组缺损区植入PCL-Gt/PCL膜,实验组缺损区植入PCL-Gt/PCL-辛伐他汀膜。分别于术后4、12周处死各组动物,行Micro-CT、HE染色等检测。结果：扫描电镜结果提示所获得的PCL-Gt/PCL-辛伐他汀电纺膜呈多层纤维交错结构,不同组织面具有不同的孔径,所载的辛伐他汀能够稳定、缓慢释放长达28天。Micro-CT检测及HE染色结果显示,实验组新生骨形成及骨缺损愈合情况显著优于阴性对照组及空白组(P<0．05)。结论：实验表明PCL-Gt/PCL-辛伐他汀膜具有明显的促进成骨能力,防止纤维细胞长入缺损区,可加速骨缺损的修复效果,提高修复质量。     

不同孔径新型复合材料硅／磷酸钙修复骨缺损实验研究

目的：探讨不同孔径新型复合材料硅，磷酸钙植入兔下颌骨缺损区的成骨能力。方法：将3种不同孔径硅膦酸钙（大孔型300μm、150μm及致密型）分别植入兔下颌骨缺损区。分别在术后3、6、12周取材进行大体、组织学观察及新骨形成的统计学分析。结果：3种不同孔径硅，磷酸钙在12周均能与邻近骨组织骨性结合：2种大孔型硅，磷酸钙新生骨面积百分比均显著大于致密型硅，磷酸钙（P〈0．01）。结论：大孔型硅，磷酸钙骨引导性、成骨活性优于致密型硅，磷酸钙。     

膜诱导组织再生技术治疗牙根尖周区骨腔缺损的实验研究

目的:利用外科手术造成的犬牙根尖周区骨腔缺损模型,观察应用膜诱导组织再生技术后骨组织再生修复的效果。方法:应用外科手术造成4只犬双侧1、2、3磨牙根尖区骨腔缺损分别为10 mm×10 mm,3个月后双侧进行根尖周刮治术,一侧应用胶原膜为实验组,另一侧未用为对照组,分别于3、6、12月拍摄X线片,观察骨腔愈合效果。结果:结果显示实验组骨腔缺损于3月后愈合,与对照组有显著性差异。结论:表明可应用膜诱导组织再生技术治疗牙根尖周区骨腔缺损。     

Simvastatin enhances bone formation around titanium implants in rat tibiae

Summary Statins are cholesterol‐lowering drugs that have been reported to promote bone formation. The purpose of this study was to investigate the effect of simvastatin on the enhancement of bone formation around titanium implants. Thirty‐week‐old female rats received pure titanium implants in both tibiae. The animals were intra‐peritoneally administered 0, 0·125, 1, 5 or 10 mg kg^?1 of simvastatin daily. After 30 days, the animals were sacrificed, and specimens were prepared. The bone contact ratio of the implant, bone density in the medullary canal and percentage of cortical bone were obtained. Markers for bone turnover were also measured using sera collected at the time of euthanasia. In the medullary canal, a scanty amount of bone was observed in the 0, 0·125 and 1 mg kg^?1 groups. In contrast, in both the 5 and 10 mg kg^?1 groups, thicker bone trabeculae were abundant. Histometric observations showed that the bone contact ratio and the bone density of both groups were significantly greater than those of the other groups (anova , P < 0·01). However, no significant difference in the percentage of cortical bone was found between groups. Serum chemistry showed that statin increased bone formation markers and decreased bone resorption markers. In conclusion, although the dose equivalent to that used in human patients with hypercholesterolemia was not effective, a simvastatin dose of 5 mg kg^?1 or higher increased medullary bone formation around the titanium. In contrast, no effect of simvastatin on pre‐existing cortical bone was indicated.     

天然羟基磷灰石-壳聚糖复合材料修复骨缺损的实验研究

目的　观察天然羟基磷灰石-壳聚糖复合材料作为骨修复材料的可能性。方法　12只新西兰白兔随机分成4组,在一侧胫骨设计两处方形缺损,其中一处植入相应大小的复合材料,另一处作为空白对照。分别于第2、4、8、12周末处死动物并取标本,行肉眼及组织学观察。结果　复合材料植入区未见明显排斥反应,术后2周可见到轻微的炎症反应,其余各组未见明显的异物巨细胞反应,术后2～8周复合材料周围的纤维包囊逐渐变薄,术后12周时可见复合材料和受植骨床形成部分骨性连接。结论　天然羟基磷灰石-壳聚糖复合材料有良好的生物相容性、骨引导活性和潜在的骨诱导作用。     

富血小板血浆修复种植体周围骨缺损的实验研究

目的探讨富血小板血浆(platelet-rich plasma,PRP)修复种植体周围骨缺损的能力。方法Beagle犬4只,拔除单侧下颌1、2、4前磨牙作为实验牙位。3个月后植入种植体,其周围制备骨缺损并植入相应骨移植材料:实验组植入PRP/磷酸三钙(tricalcium phosphate,TCP);对照组植入TCP。8、16周分别处死动物2只,进行组织学、扫描电镜观察,观察新骨形成和种植体-新骨界面情况,能谱分析种植体-新骨界面Ca含量。结果8周及16周通过肉眼及组织学观察,实验组修复效果优于对照组,种植体-新骨界面Ca含量均高于对照组,差异有显著性(P<0.05)。结论PRP/TCP作为修复种植体周围骨缺损的骨移植材料具有可行性。     

四环素骨诱导活性材料整复牙槽缺损的实验研究

目的将盐酸四环素处理的人离体非功能牙块用于诱导骨再生技术中,观察和比较其对牙槽骨再生修复的影响。方法拔除大鼠第一磨牙近中根做人工牙槽缺损。置入盐酸四环素处理的离体人牙块,以盐酸处理的离体人牙块为阳性对照,未做任何处理的离体人牙块为阴性对照。不同时期取材做组织观察和评价。结果四环素处理组炎症反应小,早期成骨明显。中晚期成骨量明显高于对照组。结论盐酸四环素处理的人离体非功能牙块有抑制骨吸收,诱导、促进牙槽骨再生等作用。     

Cyclooxygenase-2 inhibitor reduces simvastatin-induced bone morphogenetic protein-2 and bone formation in vivo

BACKGROUND AND OBJECTIVE: Simvastatin, a cholesterol-lowering drug, also stimulates oral bone growth when applied topically, without systemic side-effects. However, the mechanisms involved in vivo are not known. We hypothesized that bone morphogenetic protein-2, nitric oxide synthase, and cyclooxygenase-2 are involved, based on prior in vitro evidence. MATERIAL AND METHODS: A rat bilateral mandible model, where 0.5 mg of simvastatin in methylcellulose gel was placed on one side and gel alone on the other, was used to quantify nitric oxide, cyclooxygenase-2 and bone morphogenetic protein-2 (via tissue extraction, enzyme activity or immunoassay), and to analyze the bone formation rate (via undecalcified histomorphometry). Cyclooxygenase-2 and nitric oxide synthase inhibitors (NS-398 and L-NAME, respectively) were administered intraperitoneally. RESULTS: Simvastatin was found to stimulate local bone morphogenetic protein-2, nitric oxide and the regional bone formation rate (p < 0.05), whereas NS-398 inhibited bone morphogenetic protein-2 and reduced the bone formation rate (p < 0.05). CONCLUSION: These data suggest an association between simvastatin-induced bone morphogenetic protein-2 and bone formation in the mandibular microenvironment, and the negative effect of cyclooxygenase-2 inhibitors on bone growth.     

脱细胞脱钙人牙用于大鼠颅盖骨缺损修复的实验研究

目的: 探讨脱细胞脱钙牙作为骨支架材料的可行性和诱导大鼠颅盖骨缺损成骨能力。方法: 离体人牙24颗,分别进行脱钙和脱钙脱细胞处理。实验1—取6只10~12周龄雄性SD大鼠,在大鼠腹部皮下同时包埋脱钙牙、脱细胞脱钙牙,4周后处死大鼠,进行H-E染色,观察2种材料周围炎症反应情况。实验2—取12只10~12周龄雄性SD大鼠,制备双侧颅盖骨区域骨缺损,在左侧骨缺损处植入脱细胞脱钙牙,以未植入任何材料的右侧作为空白对照,4周、8周时分别处死6只,获取完整标本,进行Micro-CT扫描,从大体形态学上比较成骨量。取4周大鼠进行H-E染色,观察周围炎症反应,免疫组织化学观察新生成骨程度。采用SPSS 23.0软件包进行重复测量方差分析。结果: 实验1—4周时H-E染色显示,脱细胞脱钙牙与周围组织炎症反应程度显著小于脱钙牙。实验2—取4周和8周的大鼠颅盖骨进行Micro-CT扫描和骨缺损处新生骨量定量分析,显示植入脱细胞脱钙牙的骨缺损处成骨量显著多于空白对照组量（P<0.05）。4周时H-E染色结果显示,脱细胞脱钙牙周围的炎症反应程度与空白对照处相似。免疫组织化学染色显示,脱细胞脱钙牙周围新生的成骨细胞显著多于空白对照组。结论: 脱细胞脱钙人牙是一种具有良好生物相容性、成骨诱导能力和可塑性的生物支架材料。     

Bone formation after implantation of autolysed antigen extracted allogeneic bone in ovariectomized rabbits

This study was undertaken to evaluate the bone formation response to AAA bone in healthy and oestrogen deficient animals. Seventeen young healthy New Zealand female rabbits were used. Nine rabbits were subjected to ovariectomy and the remaining eight were sham-operated. Four weeks after ovariectomy standardized round cavities, 5mm in diameter, were made medially in the cortical part of each proximal tibia. To half of the cavities autolysed antigen-extracted allogeneic AAA bone granules were added. After another 8 weeks the animals were sacrificed and sections of the tibial experimental areas were obtained. These were studied in light microscopy and the bone and non-bone areas were measured with computer support.The study showed that the addition of a bone inductive substance such as AAA bone enhances bone formation also in oestrogen deficient animals.     

Simvastatin therapy in cyclosporine A-induced alveolar bone loss in rats

Background and Objective:  Cyclosporine A treatment is important in the therapy of a number of medical conditions; however, alveolar bone loss is an important negative side-effect of this drug. As such, we evaluated whether concomitant administration of simvastatin would minimize cyclosporine A-associated alveolar bone loss in rats subjected, or not, to experimental periodontal disease.
Material and Methods:  Groups of 10 rats each were treated with cyclosporine A (10 mg/kg/day), simvastatin (20 mg/kg/day), cyclosporine A and simvastatin concurrently (cyclosporine A/simvastatin) or vehicle for 30 days. Four other groups of 10 rats each received a cotton ligature around the lower first molar and were treated similarly with cyclosporine A, simvastatin, cyclosporine A/simvastatin or vehicle. Calcium (Ca²⁺), phosphorus and alkaline phosphatase levels were evaluated in serum. Expression levels of interleukin-1β, prostaglandin E₂ and inducible nitric oxide synthase were evaluated in the gingivomucosal tissues. Bone volume and numbers of osteoblasts and osteoclasts were also analyzed.
Results:  Treatment with cyclosporine A in rats, with or without ligature, was associated with bone loss, represented by a lower bone volume and an increase in the number of osteoclasts. Treatment with cyclosporine A was associated with bone resorption, whereas simvastatin treatment improved cyclosporine A-associated alveolar bone loss in all parameters studied. In addition, simvastatin, in the presence of inflammation, can act as an anti-inflammatory agent.
Conclusion:  This study shows that simvastatin therapy leads to a reversal of the cyclosporine A-induced bone loss, which may be mediated by downregulation of interleukin-1β and prostaglandin E₂ production.     

提取并部分纯化bBMP促进节段性骨缺损愈合的定量组织学研究

目的　从小牛骨基质中提取并部分纯化bBMP ,以促进节段性骨缺损的愈合。方法　通过SDS PAGE电泳及生物活性鉴定实验 ,证实bBMP保留了其活性蛋白成分 ,具有良好的骨诱导活性。在此基础上 ,合成一种新型复合人工骨材料即HA bBMP Co ,用以整复家兔尺骨中段 1.5cm节段性骨缺损 ,并对缺损区新骨生长量进行定量组织学测定。结果　HA bBMP Co复合人工骨植入整复节段性骨缺损 ,其新骨生长量明显高于同期HA Co复合人工骨组 (P <0 .0 1)。结论　HA bBMP Co复合人工骨能有效地促进节段性骨缺损的愈合 ,是一种具有良好应用前景的骨替代材料