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1.
目的:研究辛伐他汀对人牙髓干细胞成骨活性的影响.方法:将体外分离培养的人牙髓干细胞分别接种于含有不同浓度辛伐他汀的矿化培养液中诱导培养,测定碱性磷酸酶活性及骨唾液酸蛋白基因的表达情况.结果:与对照组比较,适宜浓度辛伐他汀(1×10^-6mol/L、1×10-7mol/L、1×10-8mol/L)促进人牙髓干细胞的成骨活性作用更为明显,差异具有统计学意义(P<0.05),当辛伐他汀浓度为1×10-7mol/L时,促进作用最显著.结论:适宜浓度的辛伐他汀可以有效促进人牙髓干细胞的成骨活性.  相似文献   

2.
目的寻找抗感染的块型重组合异种骨制备工艺简便的药物缓释方式,一期修复感染性长段骨缺损。方法将载药的自凝固磷酸钙骨水泥(calcium phosphate cement,CPC)分4柱置人块型重组合异种骨(massive reconstituted bone xenograft,MRBX),制成CPC载药核心的块型重组合异种骨(CPC—MRBX)。用18只成年大白兔行体内缓释实验。按照术后1、2、5、10、15、20、25、30和35d分为9组,每组2只。将CPC—MRBX植入兔骶棘肌肌袋中,按各时间点测定动物的血药浓度,并从植骨处取软组织测定植骨区周围的药物浓度。动物模型采用兔股骨感染长段骨缺损模型,共40只。外固定架位于膝上1.5~2.0cm,邻近截骨处的固定针距离截骨端0.5~0.8cm,针道方向垂直于股骨前外侧面,并在植人材料后适当加压。实验组(n=25)用CPC—MRBX修复,对照组(n=15)将自体骨段回植。术后观察动物饮食、活动和伤口的变化;在4、8、16和24周分别行影像学、组织学观察两组骨愈合情况。结果CPC—MRBX的制备过程在常温、常压下顺利完成,体内药物缓释实验显示组织中有效药物浓度可以维持30d左右,同时血药浓度无明显增高。动物模型的固定方法可靠,术后实验组动物一般情况可。术后4d动物能够正常站立,X线片示有明显的骨痂生成;8周时X线片示骨痂进一步增多,骨折线消失,可去除外固定架负重,以后功能活动基本正常。组织学4周时可见大量软骨组织长入载体;8周时新生骨组织进一步增多,CPC已有明显降解;16周时骨组织进一步增多,骨髓组织生成,CPC进一步降解;24周时髓腔再通,CPC基本降解完全。对照组4周时出现明显的骨髓炎表现,伤口局部脓性渗出,动物呈屈髋屈膝保护性体位,X线片示植骨处无愈合迹象,皮质变薄,2只针道处有骨折发生,光镜下可见明显的炎性细胞浸润和骨皮质溶解;8周前动物全部死亡,4只心脏无菌采血培养金葡菌阳性。结论CPC—MRBX制备工艺简便,且具有良好的抗感染、骨诱导和骨传导能力,能够修复有感染的长段骨缺损。  相似文献   

3.
目的探讨银杏叶提取物(Ginkgo Biloba Extract,GBE)不同体内给药方式对骨质疏松(Osteoporosis,OP)大鼠成骨的影响。方法构建去势大鼠骨质疏松模型(osteoporosis in ovariectomized rats,OVX)64只和糖皮质激素性骨质疏松大鼠模型(Glucococticoid-induced osteoporosis in rats,GIOP)64只。并将两组骨质疏松大鼠用随机数字表法分为3组不同浓度灌胃给药(100 mg/(kg·d)、200 mg(kg·d)、400 mg(kg·d)和3组注射给药(3.5 mg/(kg·d)、4.0 mg/(kg·d)、4.5 mg/(kg·d)),设立模型对照组2组,空白对照组1组(每组8只)。采用ELISA染色法检测血清骨钙素(OC)、抗酒石酸酸性磷酸酶(TRAP),观察股骨横切HE染色病理改变。结果与对照组相比,两组大鼠构模2个月后,OC、TRAP水平检测,大鼠股骨远端横断观察,符合骨质疏松改变。两组骨质疏松模型通过不同方式和浓度的给药后,与不给药对照组相比,OC水平上升(P0.01),TRAP水平下降(P0.05)。组织学观察可见,两组大鼠给药后均有不同程度新生骨小梁形成,骨小梁排列整齐,有不同程度的变粗,数量增多。结论 GBE灌胃给药与腹腔注射给药对骨质疏松大鼠的成骨均有促进作用,促进成骨细胞分泌OC,抑制破骨细胞的分泌TRAP,可以促进骨小梁的形成,增强骨的致密度,作用效果与给药方式和剂量有直接关系。  相似文献   

4.
目的 观察辛伐他汀对绝经后骨质疏松症女性骨折术后骨密度、骨折愈合及骨代谢的影响。方法 回顾分析2015年6月至2018年6月在华北医疗健康集团峰峰总医院邯郸院区住院手术治疗骨折的298例绝经后骨质疏松症女性病人的临床资料,依据病人术后是否应用辛伐他汀(20 mg·d-1)分为治疗组(76例)和对照组(222例)。分析比较两组病人术后3个月骨折愈合情况,术前、术后1年的骨密度及血清骨代谢指标。结果 术后3个月,治疗组和对照组的骨折愈合率分别为90.79%、90.54%,组间比较,差异无统计学意义(P>0.05)。术后1年,两组的骨密度、血钙、血磷、骨碱性磷酸酶(BALP)、骨钙素(OC)、抗酒石酸酸性磷酸酶(TRACP)及Ⅰ型胶原交联氨基末端肽(CTX-1)水平比较,差异无统计学意义(P>0.05)。结论 术后1年内辛伐他汀对绝经后骨质疏松女性骨折愈合、骨密度、骨代谢无显著影响。  相似文献   

5.
目的 研究骨质疏松大鼠尾椎局部注射辛伐他汀刺激成骨的效果,探索疏松椎体局部给药,重 点强化,预防脆性骨折的治疗方法。方法 36只3月龄雌性SD大鼠双侧卵巢切除后加低钙饮食3 个月,制备大鼠骨质疏松模型。实验大鼠随机分为3组,每组12只,分别在实验大鼠的第5、6、7尾椎 内(C5-C7)单次注射空白载体、辛伐他汀溶液1mg、2mg。分别在术后12天及24天每组随机处死半数大鼠(n=6 )并取材。Micro-CT扫描并定量分析骨组织形态改变、骨生物力学测试研究骨骼力学性能的变化。结果 辛伐他汀局部注射后仅12天辛伐他汀注射组骨微结构参数如骨皮质厚度、骨小梁 密度及连接率明显优于对照组,椎体力学性能明显高于对照组,术后24天效果依然明显。结论 骨质疏松大鼠尾椎单次注射小剂量辛伐他汀(1mg与2 mg)可快速、强效地促进皮质骨形成及骨小梁改 建,改善骨骼微结构,提高骨强度,可作为强化局部、防治椎体骨质疏松骨折的新选择。  相似文献   

6.
7.
目的 观察辛伐他汀对去卵巢大鼠腰椎椎体骨形成功能的影响,评价辛伐他汀对躯干骨骼的骨质疏松是否具有预防和治疗作用。方法 6月龄雌性SD大鼠60只,每组10只,50只切除双侧卵巢分为剂量组和对照组,另10只作为假手术平行对照组。以不同剂量辛伐他汀(5mg、10mg 、20mg 及40mg /kg/d)灌胃。三个月后分别行腰4椎体的双能X线骨密度测试,周围定量CT(pQCT)纵向扫描和腰5椎体的生物力学压缩测试。结果 (1)骨密度和pQCT扫描值:10mg、20mg剂量组数值较高,但皆无统计学差异。(2)生物力学测试:10mg、40mg剂量组数值较高,但无统计学差异。结论 辛伐他汀10mg/kg/d灌胃组(相当人体口服辛伐他汀12 mg~24mg/天)在多数指标中好于其它剂量组,但未发现明显统计学差异。说明辛伐他汀对去卵巢大鼠的躯干骨骼并不具有明显的骨形成促进作用,即对脊柱椎体的骨质疏松并不具有预防和治疗的作用。  相似文献   

8.
目的探讨辛伐他汀联合阿仑膦酸钠干预对去卵巢大鼠骨质疏松骨代谢的影响。方法 60只雌性SD大鼠随机平均分为5组:假手术组、去势组、辛伐他汀组、阿仑膦酸钠组、联合药物组,首先构建去卵巢大鼠骨质疏松性模型。分别检测骨代谢相关生化指标、氧化应激生化指标和骨组织骨密度(bone mineral density,BMD),HE染色观察骨组织形态学。结果去势组大鼠血清Ca、P、SOD、CAT和骨组织BMD均较假手术组显著降低(P0.05),辛伐他汀组、阿仑膦酸钠组、联合药物组上述指标均较去势组升高,以联合用药组升高最显著(P0.05)。去势组大鼠血清ALP、BGP、PICP、TRAP、GLA、ICIP和MDA较假手术组均显著增高(P0.05),辛伐他汀组、阿仑膦酸钠组、联合药物组上述指标较去势组均降低,以联合用药组降低最显著(P0.05)。去势组股骨骨小梁明显稀疏,连接不完整,大量纤维组织,髓腔内大量空泡状脂肪细胞。联合药物组骨小梁数目明显增多,结构较完整,粗细均匀致密,连接成网状。结论辛伐他汀联合阿仑膦酸钠通过调节去卵巢大鼠骨代谢,抗氧化应激,增加骨密度,改善骨组织结构,发挥抗骨质疏松作用。  相似文献   

9.
目的 研制载药骨基质明胶缓释体 ,为人工关节感染和松动的防治提供新方法。方法 将BMG溶于头孢唑林钠溶液 ,通过真空吸附、冻干等处理 ,制得载药BMG。测定其体内、体外释药浓度及持续时间以及载药BMG的诱导成骨能力。结果 载药BMG体外对金葡菌的抑制作用为 2 2d ,体内为 14d。载药BMG体内释药时 ,局部组织浓度高 ,血浆浓度低 ;局部组织早期浓度高 ,以后为稳定的低浓度释放。载药BMG中掺入抗生素后不影响BMG的诱导成骨能力。结论 载药BMG既能持续释放有效浓度的抗生素 ,又具有强的诱导成骨能力 ,可望成为防治人工关节感染和松动的一种新方法。  相似文献   

10.
载药骨基质明胶缓释体的研制与实验   总被引:6,自引:0,他引:6  
  相似文献   

11.
Acute and chronic osteomyelitis can be difficult to treat by conventional means. Current methods of treatment involve the use of systemic antibiotics, the local implantation of non-degradable drug carriers, and surgical débridement. Each method has specific drawbacks. We report on the use of a new controlled release system utilizing gentamicin and bioerodible, biocompatible polymers (polyanhydrides) designed for drug delivery applications for the treatment of clinical osteomyelitis. We compared this system's ability to reduce bacterial levels in infected bone with that of conventional non-degradable delivery systems based on polymethylmethacrylate (PMMA) and gentamicin. Polyanhydride copolymers of bis-carboxyphenoxypropane and sebacic acid P loaded with gentamicin sulfate and PMMA/gentamicin matrices were implanted in the long bones of Sprague-Dawley rats infected with a strain of Staphylococcus aureus. After 3 weeks of implantation, the polymeric delivery devices were removed and quantitative cultures were used to determine bacterial levels in bone. The polyanhydride/gentamicin matrices demonstrated significant degradation over the 3 week implantation period. Levels of bacteria, measured in colony forming units, were significantly lower in bone implanted with the polyanhydride/gentamicin release system than in long bones of control animals without an implant (p ≤ 0.01) of animals with a polyanhydride polymer implant alone (p ≤ 0.01), and of animals with a PMMA/gentamicin implant (p =0.03). Bioerodible polyanhydrides show promise as a new treatment modality for infections in bone.  相似文献   

12.
We describe a self-contained system for the continuous infusion of drugs into the rat urinary bladder. A reversible model of hydronephrosis is used to prepare one renal unit for nephrostomy tube placement. An 0.8 mm. silastic nephrostomy tube is introduced into the hydronephrotic kidney via a 16 gauge angiocath. The nephrostomy tube is then connected to an Alzet mini osmotic pump which is implanted in a subcutaneous location. The ability of this system to deliver a continuous dose of a test agent into the bladder was evaluated. Pumps were filled with a 1% solution of methylene blue in phosphate buffered saline. Following pump implantation, urinary samples were collected on a daily basis and subsequently analyzed for their concentration of methylene blue. At the completion of the experiment, specimens of the kidney, ureter, and bladder were histologically examined. Results demonstrated an average of 102% recovery of the theoretically delivered dose over a 14-day period. Renal histology demonstrated chronic inflammatory changes at the site of nephrostomy tube placement. No upper or lower tract urothelial changes were identified. This model provides a system for the continuous delivery of drugs in the rat urinary tract and results in no histological alteration to the lower urinary tract.  相似文献   

13.
Fracture healing is a complex process, which is further complicated if the bone is osteoporotic. Calcium is one of the important minerals in bone and has been found to prevent osteoporosis but its role in fracture healing of osteoporotic bone is still unclear. We carried out a study on the effects of calcium supplementation on the late phase healing of fractured osteoporotic bone using an ovariectomized rat model. Twenty‐four female Sprague–Dawley rats were divided into three groups: sham‐operated (SO), ovariectomized‐control (OVXC), and ovariectomized + calcium supplements (Ca). The right femurs of all the rats were fractured at mid‐epiphysis and a K‐wire was inserted for internal fixation. After 2 months of treatment, the rats were sacrificed and the femora were dissected out for radiological and biomechanical assessment. As expected, osteoporosis resulted in impaired healing as shown by the poor radiological and biomechanical properties of the OVXC group. CT scans showed significantly lower callus volumes in the SO and Ca groups compared to the OVXC group. Radiological scoring of fracture healing and callus staging of the SO and Ca groups were better than the OVXC group. However, the biomechanical parameters of the Ca group were significantly lower than the SO group and similar to the OVXC group. Therefore, calcium supplements may appear to improve fracture healing of osteoporotic bone but failed to improve strength. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1651–1656, 2010  相似文献   

14.
The Lipospheres Bupivacaine Delivery System (bupivacaine-lipospheres) is a novel sustained-release local anesthetic preparation that has recently been made available for research purposes. This investigation compared the local anesthetic efficacy and safety of 2% bupivacaine-lipospheres, 0.5% bupivacaine plus 1:200,000 epinephrine, lipospheres plain, and physiologic saline following subcutaneous tail injection in the rat. A modified tail-flick paradigm was used to assess local anesthetic efficacy. Animals treated with 2% bupivacaine-lipospheres or 0.5% bupivacaine with epinephrine displayed significant antinociception (P < 0.05) compared to saline or lipospheres plain with 5 min of injection. Bupivacaine with epinephrine had an anesthetic duration of 30 min, whereas 2% bupivacaine-lipospheres had a duration of 3 hr. The local anesthetic blockade produced by both active solutions was completely reversible. All animals gained weight normally during the 1-wk course of the study, and there were no signs of local tissue toxicity at the injection sites. We conclude that 2% bupivacaine-lipospheres is a safe and efficacious local anesthetic preparation in this particular animal model. It possesses an onset of action that is a rapid as 0.5% bupivacaine with 1:200,000 epinephrine, and a duration that is six times longer.  相似文献   

15.
目的 探讨辛伐他汀对脓毒症大鼠内皮细胞功能的影响.方法清洁级雌性Wistar大鼠96只,体重200~250异,月龄4月.采用随机数字表法,将大鼠随机分为3组(n=32):假手术组(Ⅰ组)、脓毒症组(Ⅱ组)和辛伐他汀组(Ⅲ组).选模前,Ⅲ组经胃管给予辛伐他汀20 mg/kg,1次/d,连续2周,Ⅰ组和Ⅱ组用等容量生理盐水替代.Ⅱ组和Ⅲ组采用盲肠结扎穿孔法制备脓毒症模型.于术后3、6、24及48 h时分别取8只大鼠,采集颈动脉血样,测定血常规,计数WBC,用ELISA法检测血清B选择素浓度.结果 与Ⅰ组比较,Ⅱ组和Ⅲ组WBC计数和血清B选择素浓度升高,术后6 h时达峰值(P<0.05);与Ⅱ组比较,Ⅲ组WBC计数和血清E.选择素浓度降低(P<0.05).结论 辛伐他汀治疗脓毒症的作用机制与保护内皮细胞功能有关.
Abstract:
Objective To investigate the effect of simvastatin on endothelial cell function in a rat model of sepsis. Methods Ninety-six pathogen-free female Wistar rats aged 4 months weighing 200-250 g were randomly divided into 3 groups (n = 32 each): group sham operation (group Ⅰ ); group sepsis (group Ⅱ )and group simvastatin + sepsis(group Ⅲ ) . Sepsis was induced by cecal ligation and puncture (CLP). In group Ⅲ simvastatin 20 mg/kg was given via a gastric tube once a day for 2 weeks. Blood samples were taken from carotid artery at 3,6, 24 and 48 h ( n = 8 at each time point) for WBC count and measurement of serum E-selectin concentration (by ELISA) . Results CLP significantly increased WBC count and serum E-selectin concentration in group Ⅱ as compared with group Ⅰ . The peak values were reached at 6 h after operation. Simvastatin pretreatment attenuated the sepsis-induced increase in WBC count and serum E-selectin concentration in group Ⅲ. Conclusion Protection of endothelial cell function is involved in the mechanism of treatment of sepsis with simvastatin.  相似文献   

16.
Abrahams JM  Forman MS  Grady MS  Diamond SL 《Neurosurgery》2001,49(5):1187-93; discussion 1193-5
OBJECTIVE: We designed biodegradable polyglycolide coils (BPCs) and compared the histopathological response to the coils with that to platinum Guglielmi detachable coils (GDCs), after insertion into ligated common carotid arteries (CCAs) of adult rats. BPCs were also tested for use in local drug delivery. METHODS: Segments (4-mm) of unmodified BPCs, unmodified GDCs, or BPCs coated with Type I bovine collagen and recombinant human vascular endothelial growth factor-165 (500 microg/ml) were inserted into ligated CCAs of adult rats for 14 days, and specimens were compared with contralateral CCA control specimens. RESULTS: Arterial segments with BPCs exhibited substantially increased wall thickening, compared with GDCs (0.33 mm versus 0.10 mm, P < 0.005), which reduced the luminal diameter by 40%, relative to untreated contralateral control specimens (P < 0.05, n = 6). Arterial segments with BPCs also exhibited a marked reduction (P < 0.05, n = 6) in luminal area (0.72 +/- 0.93 mm(2)), with marked cellular proliferation within the coil diameter, indicating coil integration. Arterial segments with collagen/recombinant human vascular endothelial growth factor-coated BPCs also exhibited a marked 2.9-fold increase (P < 0.005, n = 5) in wall thickness (0.29 +/- 0.11 mm) and a 34% reduction in luminal diameter, compared with contralateral control vessels. There was marked proliferation of cells within the coil lumen of vessels treated with BPCs with collagen/recombinant human vascular endothelial growth factor. CONCLUSION: In this feasibility study, BPCs enhanced the vascular response of CCA segments, compared with GDCs, and were also suitable for local protein delivery to the vessel lumen, under conditions of stasis and arterial pressurization of vascular cells.  相似文献   

17.
Osteoporotic fractures commonly occur in the elderly. Although current therapies are aimed at the prevention and treatment of osteoporotic fractures, studies examing the fracture healing process in osteoporotic bone are limited. We produced an osteoporotic rat model by ovariectomy (ovx) and maintained a low calcium diet (LCD) in order to evaluate the influence of osteoporosis on fracture healing. Callus formation and strength was monitored over a 3 week period by histological and biomechanical assessment. Data collected simultaneously on a group of rats undergoing sham surgery (sx) were used for comparison. A 40% reduction in fracture callus cross-sectional area and a 23% reduction in bone mineral density in the healing femur of the ovx rats was observed on day 21 following fracture as compared with the sx group (p < 0.01). Biomechanical data from the healing femur of the ovx rats revealed a fivefold decrease in the energy required to break the fracture callus, a threefold decrease in peak failure load, a twofold decrease in stiffness and a threefold decrease in stress as compared with the sx group (p < 0.01, respectively). Histomorphological analysis revealed a delay in fracture callus healing with poor development of mature bone in the ovx rats. This study provides physical evidence of altered fracture healing in osteoporotic bone, which may have important implications in evaluating the effects of new treatments for osteoporosis on fracture healing.  相似文献   

18.
The high prevalence of tendon retear following rotator cuff repair motivates the development of new therapeutics to promote improved tendon healing. Controlled delivery of non-steroidal anti-inflammatory drugs to the repair site via an implanted scaffold is a promising option for modulating inflammation in the healing environment. Furthermore, biodegradable nanofibrous delivery systems offer an optimized architecture and surface area for cellular attachment, proliferation, and infiltration while releasing soluble factors to promote tendon regeneration. To this end, we developed a bilayer delivery system (BiLDS) for localized and controlled release of ibuprofen (IBP) to temporally mitigate inflammation and enhance tendon remodeling following surgical repair by promoting organized tissue formation. In vitro evaluation confirmed the delayed and sustained release of IBP from Labrafil-modified poly(lactic-co-glycolic) acid microspheres within sintered poly(ε-caprolactone) electrospun scaffolds. Biocompatibility of the BiLDS was demonstrated with primary Achilles tendon cells in vitro. Implantation of the IBP-releasing BiLDS at the repair site in a rat rotator cuff injury and repair model led to decreased expression of proinflammatory cytokine, tumor necrotic factor-α, and increased anti-inflammatory cytokine, transforming growth factor-β1. The BiLDS remained intact for mechanical reinforcement and recovered the tendon structural properties by 8 weeks. These results suggest the therapeutic potential of a novel biocompatible nanofibrous BiLDS for localized and tailored delivery of IBP to mitigate tendon inflammation and improve repair outcomes. Future studies are required to define the mechanical implications of an optimized BiLDS in a rat model beyond 8 weeks or in a larger animal model.  相似文献   

19.
目的通过骨质疏松性骨折动物模型,观察阿仑膦酸钠、强骨胶囊单用及合用对骨折愈合的影响,以探讨中西医结合治疗骨质疏松性骨折的意义。方法 70只SD大鼠给予维甲酸灌胃,制造骨质疏松性骨折模型成功后分别予以阿仑膦酸钠、强骨胶囊及两药合用,于2周、4周和6周处死5只试验鼠,进行骨痂大小的测量及组织学研究。结果 2周时合用组骨痂大小较其他组无显著差异;4周时合用组骨痂大小较阿仑膦酸钠组小,较强骨胶囊组大;6周时各组骨痂大小无异。组织学检测发现阿仑膦酸钠组破骨细胞数目最少,骨小梁成熟较其他组缓慢;强骨胶囊组成骨细胞数目最多,小梁骨成熟最快;强骨胶囊联合阿仑膦酸钠组与对照组无差别。结论强骨胶囊与阿仑膦酸钠联合使用治疗维甲酸所致大鼠骨质疏松性骨折疗效并不显著。  相似文献   

20.
 目的 探讨疏松骨骼局部注射辛伐他汀对内固定强度的影响及其作用机制。方法 取3月龄雌性SD大鼠24只,切除双侧卵巢制备大鼠骨质疏松模型。3个月后将动物随机分为三组。右侧股骨髁植入钛合金螺钉后于髓腔内分别注射5 mg、10 mg辛伐他汀或空白PBS缓冲液。术后1个月行骨密度测定、螺钉周围骨微结构定量分析,测定螺钉最大载荷,通过免疫组织化学染色观察BMP-2的表达。结果 辛伐他汀5 mg组、10 mg组骨密度分别为(201±23.3)、(207.9±23.5) mg/cm2,与空白PBS缓冲液组(170.8±13.8) mg/cm2比较差异有统计学意义;螺钉骨整合率分别为51.4%±3.0%、52.6%±4.1%,较空白PBS缓冲液组(27.3%±4.9%)增加,螺钉周边各项骨微结构指标均改善,差异有统计学意义;螺钉的最大载荷分别为(161.5±9.4)、(161.9±11.4) N,高于空白PBS缓冲液组(145.7±9.6) N,差异有统计学意义;BMP-2的表达较空白PBS缓冲液组增强。结论 疏松骨骼局部单次注射小剂量辛伐他汀可促进内植物周边的骨整合,增强内固定的稳定性;其作用机制与局部注射辛伐他汀促进BMP-2的高表达有关。  相似文献   

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