卵巢切除股骨骨折大鼠骨愈合中降钙素的作用

背景：降钙素可活化腺苷酸环化酶蛋白激酶A通路及磷脂酶C通路,抑制破骨细胞的活性,可能治疗骨质疏松性骨折。 目的：观察降钙素对去卵巢大鼠股骨骨折愈合的作用。 方法：构建双侧卵巢切除骨质疏松右股骨骨折SD大鼠模型,然后分别皮下注射生理盐水和降钙素(16 IU/kg),隔日1次,于骨折后3周和6周测量右股骨行骨密度,苏木精-伊红及抗酒石酸酸性磷酸酶染色,骨形态发生蛋白2及血管内皮生长因子免疫组化染色。 结果与结论：骨折后给予降钙素治疗的大鼠抗酒石酸酸性磷酸酶染色阳性细胞积分吸光度值较生理盐水治疗的大鼠显著减少(P < 0.05)。骨折后3周,两组骨折线均较清晰,骨痂体积无明显差别,骨折愈合以软骨内化骨过程为主,骨密度无显著性差异(P > 0.05)。骨折后6周,两组骨折线较模糊,骨痂体积无差别,骨小梁排列较有序,用药组股骨骨密度较对照组升高(P < 0.05)。两组在骨折后3周和6周的骨形态发生蛋白2及血管内皮生长因子差异无显著性意义(P > 0.05)。证实降钙素可以抑制去卵巢大鼠骨折部位破骨细胞活性,但无明显促进大鼠股骨骨折愈合的作用。     

辛伐他汀局部注射对大鼠骨质疏松性骨折愈合的影响

目的： 研究辛伐他汀局部注射对去势大鼠骨折愈合的影响。方法: 2月龄雌性SD大鼠采用去势方法模拟人绝经后骨质疏松症,模型成立后进一步建立胫骨骨折髓内钉内固定模型,实验组于骨折端皮下注射辛伐他汀(10 mg·kg^-1·d^-1,5 d),另一组仅注射无辛伐他汀的溶剂作为空白对照组。骨折后1、2、4周取标本,通过X片、生物力学、组织病理学以及组织形态计量学等方法评价两组骨折愈合质量。结果: 与空白对照组相比,实验组骨痂横截面积在骨折后1周、2周分别增加21.3% (P<0.05) 和21.5% (P<0.05);骨痂最大载荷在骨折后2周、4周分别增加57.5% (P<0.05) 和31.4% (P<0.05);组织学显示实验组新生编织骨较对照组多且排列致密;组织形态计量学测量结果表明辛伐他汀可明显增加矿化宽度(MLW)、矿化容积(MLV) 以及矿化率(MAR)。结论: 局部应用辛伐他汀可促进去势大鼠骨折愈合。     

辛伐他汀涂层内固定对大鼠骨质疏松骨折愈合晚期的影响

背景：降脂类药物辛伐他汀具有一定的促进骨形成作用潜能,局部应用效果更佳。先前研究对骨质疏松大鼠骨折愈合中期的观察证实辛伐他汀涂层内固定可促进骨质疏松大鼠骨折愈合,但其对骨折愈合晚期的影响未见报道。 目的：观察局部应用辛伐他汀涂层内固定对骨质疏松大鼠骨折愈合晚期进程的影响。 方法：将雌性SD大鼠分为单纯骨折组、骨质疏松性骨折组及辛伐他汀干预组。单纯骨折组仅暴露腹腔卵巢不予切除,其余2组采用双侧卵巢切除法建立骨质疏松模型。卵巢切除后6周,所有大鼠建立股骨中段开放性骨折模型,单纯骨折组、骨质疏松性骨折组及辛伐他汀干预组分别采用无涂层、聚乳酸涂层和辛伐他汀复合聚乳酸涂层克氏针内固定。骨折造模后12周分析骨折侧股骨骨密度,X射线摄片和苏木精-伊红染色分析骨折愈合情况,免疫组织化学分析骨形态发生蛋白2在骨折局部的表达。 结果与结论：骨密度检测结果提示股骨全长及中段骨密度骨质疏松性骨折组、辛伐他汀干预组显著低于单纯骨折组,辛伐他汀干预组骨折部位骨密度显著高于骨质疏松性骨折组。X射线摄片结果提示,单纯骨折组骨折两端对位、对线良好,骨痂与骨皮质密度接近相同并相互连接,塑形基本完成;骨质疏松性骨折组愈合质量差,骨痂密度浅淡,部分标本仍见模糊的骨折线;辛伐他汀干预组骨折线消失,骨痂填满骨缺损,骨膜反应深,单纯骨折组、辛伐他汀干预组X射线评分显著高于骨质疏松性骨折组(P < 0.05)。苏木精-伊红染色提示,骨质疏松性骨折组骨折愈合进程较单纯骨折组延迟,辛伐他汀干预组骨小梁较骨质疏松性骨折组更规则有序。免疫组化结果提示各组大鼠骨形态发生蛋白2的表达水平差异无显著性意义。提示辛伐他汀局部应用可有效促进骨质疏松大鼠骨折愈合。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

辛伐他汀对去卵巢骨质疏松大鼠股骨生物力学的影响

目的研究辛伐他汀(Simvastatin,SIM)对去卵巢(OVX)骨质疏松大鼠股骨生物力学性能的影响。方法48只3月龄雌性SD大鼠,随机分成3组,假手术(SHAM)组、OVX组和OVX+SIM组,每组8只。适应性喂养一周后进行手术。术后8周开始给药,OVX+SIM组给予SIM 5mg.kg-1·d-1,其余两组用等量生理盐水灌服。用药后第4周每组随机处死半数大鼠,12周后处死剩余大鼠,取股骨进行三点弯曲试验,检测股骨最大载荷、弹性载荷、最大桡度、弹性桡度、弯曲刚度系数、弯曲韧度系数等生物力学性能。结果(1)用药4周,最大载荷:SHAM组较OVX组明显增加(P<0.05);弹性载荷:OVX+SIM组较OVX组明显降低(P<0.05);最大桡度:SHAM组较OVX组明显增加(P<0.05);弯曲韧度系数:OVX+SIM组较OVX组明显增加(P<0.01)。(2)用药12周,最大载荷:OVX+SIM组、SHAM组较OVX组明显增加(P<0.05,P<0.01);弹性载荷:OVX+SIM组较OVX组明显增加(P<0.05);弯曲韧度系数:OVX+SIM组、SHAM组较OVX组明显降低(P<0.05,P<0.01)。(3)用药12周较4周,OVX+SIM组最大载荷、弹性载简明显增加(P<0.01),OVX组弯曲韧度系数明显增加(P<0.01)。结论SIM能促进去势大鼠骨的再建,改变骨的空间微结构和骨组织有机成分和无机成分的比例及结合,随时间的延长能提高股骨的强度。     

卵巢切除对大鼠子宫雌激素受体亚型的影响

雌激素在生长、分化及雌性生殖功能中扮演重要角色.雌激素的作用是由靶细胞内雌激素受体(estrogen receptor,ER)所介导的,ER是类固醇受体超家族成员之一,它是通过与雌激素受体反应元件结合调控基因转录,而在靶细胞中发挥功能的.     

辛伐他汀对去卵巢大鼠骨痂骨保护素表达的影响

目的: 研究去卵巢及辛伐他汀(simvastatin, SVS)对大鼠骨痂骨保护素(osteoprotegerin, OPG)表达的影响。方法: 2月龄雌性SD大鼠采用去卵巢(ovariectomy, OVX)方法模拟人绝经后骨质疏松症,造模成功后进一步建立胫骨骨折髓内钉内固定模型。大鼠分为3组:假手术组(sham+vehicle)、空白组(OVX+vehicle)及实验组(OVX+SVS)。OVX+SVS组于骨折端皮下注射辛伐他汀(10 mg·kg^-1·d^-1×5 d),sham+vehicle及OVX+vehicle组仅注射无辛伐他汀的空白溶剂。骨折后1、2、4周取骨痂标本,切片免疫组化染色,分析骨痂中的增殖细胞核抗原(PCNA)、OPG表达情况。结果: 结果显示OVX+vehicle组骨折后1、2、4周PCNA阳性率较sham+vehicle组分别下降17.3%、32.1%和26.1%(P<0.01);OVX+SVS组骨折后1、2、4周PCNA阳性率较OVX+vehicle组分别增加60.1%、67.7%和67.7%(P<0.01);半定量结果显示OVX+vehicle组OPG表达水平最低,sham+vehicle组最高,而OVX+SVS组的OPG表达水平介于2组之间,OVX+SVS组与OVX+vehicle组间差异显著(P<0.01)。结论: 本实验显示去势可明显减少骨痂OPG的表达,而辛伐他汀可刺激骨痂分泌OPG,提示他汀类药物具有间接抑制破骨细胞的作用。     

卵巢切除对椎体骨力学强度的影响研究

三个月龄SD雌性大鼠64只,平均体重180～240g,作双侧卵巢切除(OVX组)和假手术(Sham-O组):术后第1,3,5,7月取L2椎体。另职新生24～72小时雌性SD鼠48只,丝线结扎切除双前肢及尾根部,建立双后肢大鼠模型。3月时再同法分OVX及Sham-O组,术后第2,5,7月时分别处死动物切取L2椎体,在测量椎体几何形态后进行垂直压缩试验,结果显示:OVX组椎体平均高度减低(P<0.05),椎体上端前后缘变大(P<0.05),OVX组1月时椎体载荷及能承受的应力等均已明显下降(P<0.01),7月时降至低值。双后肢大鼠组:力学测试显示各阶段OVX组力学强度明显下降,各力学参数呈现较正常应力组为高的趋势,可能与双后肢站立后椎体承受的应力增加有关。椎体力学强度的减低,以致即便是较小的创伤亦具有极高的骨折危险性。     

卵巢切除对四氯化碳诱导大鼠肝纤维化形成的影响

为探讨卵巢切除对CCl4 诱导大鼠肝纤维化形成的影响 ,采用CCl4 诱导雌性大鼠肝纤维化动物模型 ,观察卵巢切除及雌激素替代治疗 (苯甲酸雌二醇 1mg kg)对肝脏胶原沉积和I、Ⅲ型胶原蛋白表达的影响 ,并分别检测血清学标志及肝脏组织学等变化。结果显示CCl4 模型组大鼠肝脏发生典型的肝纤维化改变 ,卵巢切除组的肝脏胶原沉积更为明显 ,肝脏表达I、Ⅲ型胶原及血清肝纤维化指标也明显高于CCl4 摸型组 (P <0 0 5 ) ,而雌激素干预及替代治疗则可抑制肝纤维化的形成。表明卵巢切除加速CCl4 诱导大鼠肝纤维化的形成 ,其发生可能与卵巢分泌的雌激素对肝纤维化的抑制作用有关。     

辛伐他汀干预卵巢切除大鼠骨密度和生物力学性能的变化

BACKGROUND: Osteoporosis and its complications severely threaten the elder’s health. Simvastatin, widely accepted as a lipid-lowering drug, is reported to potentially promote bone formation, but it is in debate when orally administered, and there is no evidence to support whether this is due to the region difference. OBJECTIVE: To investigate the effect of orally administered simvastatin on bone mass and biomechanical properties of the femur and vertebrae in osteopenia rats induced by ovariectomy (OVX). METHODS: Twenty-four 6-month-old female Sprague-Dawley rats were subjected to OVX+orally administered saline vehicle (OVX group, n=8), OVX+orally administered simvastatin (5 mg/kg/d; intervention group, n=8) or sham surgery (sham group, n=8). After 8 weeks of treatment, all rats were sacrificed and the level of procollagen type I N-terminal propeptide in blood serum was assessed by ELISA. Bone mineral density was determined in the L5 vertebra and left femur using dual-energy X-rays. Furthermore, the biomechanical properties of the L4 vertebra and right femur, including maximum load and elastic modulus, were detected by compression testing and three-point bending test, respectively. RESULTS AND CONCLUSION: The serum level of procollagen type I N-terminal propeptide in the sham group was significantly lower than that in the other two groups. OVX rats showed significantly lower bone mineral density in both the L5 vertebra and left femur than sham rats (P < 0.05). Rats in the intervention group showed higher bone mineral density than those in the OVX group, with statistically significant difference in the L5 vertebra (P < 0.05), but insignificant difference in the femur. Maximum load and elastic modulus of the L4 vertebra in the OVX group were significantly lower than those in the sham and intervention group. Markedly lower elastic modulus of the femur was found in the OVX group than the sham and intervention groups. These findings demonstrate that simvastatin treatment can partially prevent bone loss in OVX rats with more notable effect on the vertebrae than the femur, and for this model, the vertebra is superior to the femur used in biomechanical test. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

植物雌激素对去卵巢大鼠骨质疏松性骨折愈合的影响

目的观察植物雌激素对卵巢去势大鼠骨折愈合过程中骨痂骨密度的影响。方法复制卵巢去势大鼠骨质疏松模型并制造股骨中段闭合性骨折,然后进行克氏针髓腔内固定,观察大鼠骨折内固定后骨痂与近骨痂段股骨骨密度的变化。结果异黄酮组、雌二醇组和假手术组骨痂的骨密度高于无用药组,差异具有统计学意义(P<0.05);而异黄酮组、雌二醇组和假手术组之间没有显著差别。结论植物雌激素能够显著提高骨质疏松大鼠骨痂及近骨痂段骨组织的骨密度、促进骨折愈合,与雌二醇组作用相近。     

阿仑膦酸钠可抑制骨质疏松性骨折的愈合

背景：阿仑膦酸钠作为治疗骨质疏松症的首选药物已被临床广泛应用。 目的：观察阿仑膦酸钠对骨质疏松性骨折大鼠股骨干骨折愈合的影响。 方法：将SD大鼠随机分成3组：假手术组,模型组和阿仑膦酸钠组。模型组及阿仑膦酸钠组于卵巢切除后4周进行右股骨干中段横行骨折,克氏针固定。阿仑膦酸钠组建模后皮下注射阿仑膦酸钠。 结果与结论：骨折造模后3及6周,阿仑膦酸钠组右股骨整体骨密度和远段骨密度高于模型组(P < 0.01),与模型组相比,阿仑膦酸钠组骨折端骨痂体积大、骨痂数量多,软骨性骨痂向骨性骨痂转换过程延迟,骨折愈合过程减慢,破骨细胞数量显著降低(P < 0.05)。结果证实,阿仑膦酸钠对大鼠骨质疏松性骨折愈合过程有抑制作用,其机制可能与阿仑膦酸钠抑制破骨细胞活性使骨痂钙化过程减慢有关。     

糖皮质激素对大鼠骨折愈合方式的影响

目的:探讨糖皮质激素对大鼠骨干骨折愈合方式的影响。方法:取3月龄雌性SD大鼠60只分为实验组和对照组,实验组肌肉注射醋酸强的松5mg·kg-1.d-1,对照组注射等容积的生理盐水。3周后制成胫骨干骨折模型,骨折后不同阶段处死,分别进行组织学、骨密度、Western印迹检测骨痂中Ⅱ型胶原蛋白的表达以及生物力学测定。结果:肌肉注射醋酸强的松3周后骨密度检查证实模型制造成功。骨折后第3d2组均开始形成原始骨痂;第2周实验组软骨骨痂明显比对照组少,第4-6周实验组骨痂面积高于对照组,且软骨骨痂比例较高,骨密度减低。实验组中Ⅱ型胶原蛋白表达明显延迟。第6周生物力学测定对照组实际最大载荷为(69.77±8.46)N,较实验组(51.38±3.37)N增加35.8%。结论:大剂量糖皮质激素在大鼠骨折早期延缓软骨骨痂的产生,在骨折中后期使软骨性骨痂至骨性骨痂演变过程减缓。Ⅱ型胶原蛋白的表达延迟可能是其对骨折愈合产生不利影响的原因之一。     

Effects of leptin on femoral fracture in rats

In this study, our objective was to evaluate effects of leptin on fracture healing in rats. Seventy two male SpragueDawley (SD) rats were randomized into 3 groups. Standardized femoral fractures were created in all the rats. Group A was treated with 1 mL normal saline (NS), group B with 0.3 μg/kg leptin in 1 mL NS, and group C with 0.5 μg/kg leptin in 1 mL NS for 2 weeks intraperitoneally. Each group was divided into three subgroups including 8 rats for evaluation at 2, 4 and 8 weeks. Radiological evaluation showed that callus formation of group B and C was all significantly higher than group A at 8 weeks (P = 0.04 and P = 0.013, respectively). There was no statistically significant difference in fracture healing between group B and group C at 8 weeks (P = 0.197). Histological evaluation revealed fracture healing of group B and C was better than group A at 4 weeks (P = 0.01 and P = 0.002, respectively) and 8 weeks (P = 0.008 and P = 0.003, respectively). Micro-computed tomography (Micro-CT) analysis demonstrated that greater amounts of bony callus and evidence of bone fusion were observed in group B and C at 4 weeks (P = 0.02 and P = 0.04, respectively) and 8 weeks (P = 0.005 and P = 0.001, respectively) compared to group A. Group C also had better fracture healing than group B at 8 weeks (P = 0.01). In conclusion, leptin has a positive effect on rat femoral fracture healing.     

低强度脉冲超声促进卵巢切除大鼠骨折愈合的超微结构研究

目的观察卵巢切除大鼠骨折愈合过程中细胞超微结构的变化,探讨低强度脉冲超声（Low-intensity Pulsed Ultrasound,LIPUS）促进其愈合过程的作用机理。方法60只4.5月龄的雌性SD大鼠,其中48只去势后10周证实已发生骨质疏松,建立双侧股骨中段骨折模型,按标准筛选,共34只接受治疗。造模后第2日起采用自制低强度脉冲超声仪随机对一侧后肢进行连续治疗,每天20min,超声波频率为1.5MHz,脉宽200S,重复频率1KHz,强度为50mW·cm^-2;另一侧做对照。分别在骨折后第4天和第1、2、4、6、8周各处死5只大鼠,透射电镜下观察骨痂内细胞超微结构的变化。结果与对照侧相比,治疗侧软骨细胞分化增殖明显,细胞功能活跃;成骨细胞数量增多,细胞合成功能旺盛,胶原纤维致密,矿化明显;破骨细胞极化现象多见。结论LIPUS作用于卵巢切除大鼠骨折愈合过程,促进了软骨细胞的分化成熟,刺激了成骨细胞的合成分泌以及破骨细胞的分化成熟,改善了骨折愈合的质量。     

Piper sarmentosum enhances fracture healing in ovariectomized osteoporotic rats: a radiological study

INTRODUCTION:

Osteoporotic fractures are common during osteoporotic states. Piper sarmentosum extract is known to possess antioxidant and anti-inflammatory properties.

OBJECTIVES:

To observe the radiological changes in fracture calluses following administration of a Piper sarmentosum extract during an estrogen-deficient state.

METHODS:

A total of 24 female Sprague-Dawley rats (200-250 g) were randomly divided into 4 groups: (i) the sham-operated group; (ii) the ovariectomized-control group; (iii) the ovariectomized + estrogen-replacement therapy (ovariectomized-control + estrogen replacement therapy) group, which was supplemented with estrogen (100 µg/kg/day); and (iv) the ovariectomized + Piper sarmentosum (ovariectomized + Piper sarmentosum) group, which was supplemented with a water-based Piper sarmentosum extract (125 mg/kg). Six weeks after an ovariectomy, the right femora were fractured at the mid-diaphysis, and a K-wire was inserted. Each group of rats received their respective treatment for 6 weeks. Following sacrifice, the right femora were subjected to radiological assessment.

RESULTS:

The mean axial callus volume was significantly higher in the ovariectomized-control group (68.2±11.74 mm³) than in the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups (20.4±4.05, 22.4±4.14 and 17.5±3.68 mm³, respectively). The median callus scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups had median (range, minimum - maximum value) as 1.0 (0 - 2), 1.0 (1 - 2) and 1.0 (1 - 2), respectively, which were significantly lower than the ovariectomized-control group score of 2.0 (2 - 3). The median fracture scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups were 3.0 (3 - 4), 3.0 (2 - 3) and 3.0 (2 - 3), respectively, which were significantly higher than the ovariectomized-control group score of 2.0 (1 - 2) (p<0.05).

CONCLUSION:

The Piper sarmentosum extract improved fracture healing, as assessed by the reduced callus volumes and reduced callus scores. This extract is beneficial for fractures in osteoporotic states.     

恶性外周神经鞘瘤临床与病理特征

目的　探讨恶性外周神经鞘瘤（MPNST）的临床与病理形态特征。 方法　收集本院收治的22例MPNST临床资料，应用光学显微镜观察病理形态特点，免疫组化分析其表型，并进行相关文献复习。 结果　22例MPNST中，男10例，女12例，年龄15~82岁，中位年龄43岁。头颈部3例，躯干及四肢近端13例，四肢远端5例，全身多发1例。临床表现主要是局部逐渐增大的无痛性肿块，症状与体征与肿块的部位及进展速度有关。19例患者行肿瘤切除手术，术后其中6例患者被嘱须行后续放疗，13例患者行化疗（以多柔比星和异环磷酰胺为主）。免疫组化检测，Vimentin（15/15）、CD99（8/8）、IMP3（10/11）、S-100蛋白（16/19）阳性，Ki-67增殖指数5%~80%。1年病死率45%，中位生存时间25个月。局部复发率55%（12例），远处转移率32%（7例）。末次随访3例无瘤生存。 结论　MPNST的临床及病理有其特点，但某些医生对其认识不足。本文总结辨析要点，以期提高该病确诊率，指导治疗和康复。     

新型带环克氏针张力带与普通克氏针张力带治疗粉碎性髌骨骨折的比较

目的观察对比新型带环克氏针张力带与普通克氏针张力带治疗粉碎性髌骨骨折的临床效果。方法选取本院2016年1月至2017年12月入院的87例粉碎性髌骨骨折患者作为观察对象,5例未完成随访(未纳入统计),余82例完成随访。按照随机数表法将入选患者随机分为:研究组(A组)45例,应用新型带环克氏针张力带技术治疗;对照组(B组)42例,应用普通克氏针张力带技术治疗。对比两组病例的临床数据(手术时间、术中出血量、术中透视次数、住院时间、随访时间、并发症)、术后NRS疼痛评分、膝关节AKS功能评分。结果共82例患者完成随访。其中,研究组(A组)42例,平均随访时间为(12.72±0.98)个月;对照组(B组)40例,平均随访时间为(12.96±1.16)个月。两组随访时间比较差异无统计学意义(0.05)。两组病例的手术时间、手术出血量、术中透视次数、住院时间、NRS疼痛评分、AKS评分、患者满意度的结果相似,差异无统计学意义(0.05)。两组的术后并发症:内固定松动(A组0例,B组4例,0.05)及克氏针引起的疼痛方面(A组0例,B组5例,0.05)两组比较差异有统计学意义。另外在伤口愈合不良方面(A组0例,B组1例,0.05),两组比较差异无统计学意义。结论新型带环克氏针张力带技术治疗髌骨粉碎骨折疗效可靠,能有效减少内固定松动及内固定引起的疼痛,值得临床使用和推广。