补肾方剂和氨基胍对糖尿病大鼠纯钛种植体骨结合影响作用的实验研究

目的:探讨在临床上提高糖尿病患者牙种植体的骨结合率的有效方法.方法: 建立糖尿病大鼠骨内种植模型,制作HE染色组织切片,采用光镜和骨计量学参数观察,比较补肾方剂和氨基胍对糖尿病大鼠纯钛种植体骨结合改善作用的差异.结果:注射链脲佐菌素(STZ) 3 d后大鼠空腹血糖显著升高(P<0.05),尿糖阳性. 光镜观察(种植体植入术后12 周时):糖尿病补肾方剂治疗组(中药组)结合骨板连续性较好,较厚,表面光滑,周边可见大量的成骨细胞,骨细胞密度较大.糖尿病氨基胍治疗组(西药组):结合骨板比较薄,连续性较好, 周边可见大量的成骨细胞,骨细胞密度较大.骨计量学参数比较(种植体植入术后12 周时):糖尿病组结合骨板的宽度、种植区成骨细胞数、种植区骨细胞数及非种植区骨细胞数均显著低于西药组、中药组(P<0.05).西药组结合骨板的宽度、种植区成骨细胞数、种植区骨细胞数均显著低于中药组(P<0.05).结论: 氨基胍可通过控制糖尿病,改善种植体的骨结合; 补肾方剂可通过控制糖尿病和调节骨代谢,有效促进和提高种植体的骨结合,其效果优于氨基胍.     

补肾方剂对骨质疏松大鼠纯钛种植体骨结合影响的骨计量学研究

目的:观察补肾方剂对骨质疏松大鼠纯钛种植体骨结合的影响,探讨补肾方剂促进纯钛种植体骨结合的机制。方法:选用纯种8月龄雌性SD大鼠54只,随机分为3组。A组:假手术组,B组:卵巢切除组,C组:卵巢切除加中药治疗组。在3组大鼠胫骨近中干骺端分别植入纯钛光滑柱状种植体。C组大鼠用补肾方剂灌胃。种植术后1、2、3个月,取出带种植体的胫骨,制作HE染色的组织切片,骨计量学观察。结果:C组的骨小梁宽度、结合骨板宽度、松质骨区骨量、成骨细胞数均明显大于B组(P<0.01)。结论:补肾方剂可以使骨质疏松大鼠种植体周围的成骨细胞数增加,松质骨区骨量明显增加,促进骨改建,提高骨结合的质量。     

补肾方剂对骨质疏松大鼠纯钛种植体骨结合影响的组织学观察

目的通过建立大鼠骨质疏松模型，观察补肾方剂对骨质疏松大鼠纯钛种植体骨结合的影响。方法选用纯种8月龄雌性SD大鼠54只，随机分为3组：A组：假手术组，B组：卵巢切除组，C组：卵巢切除加中药治疗组。术后3个月，在三组大鼠胫骨近中干骺端分别植入纯钛光滑柱状种植体。C组大鼠用补肾方荆灌胃。组织学观察种植体愈合情况。结果C组结合骨板厚，松质区骨小梁密集，成骨细胞较多，破骨细胞少见。C组的愈合情况明显好于B组。结论补肾方荆可以使骨质疏松大鼠的种植体周围的成骨细胞数量明显增加，促进骨改建，提高骨结合的质量，有促进种植体骨结合的作用。     

中、西药治疗实验性糖尿病牙周炎的骨计量学研究

目的:对比观察补肾方剂和氨基胍对实验性糖尿病牙周炎大鼠牙槽骨吸收的治疗作用.方法:选取纯种雄性SD大鼠随机分为4组,各30只:正常对照组(C组)、糖尿病牙周炎组(DP组)、氨基胍治疗组(AG组)及中药治疗组(TKR组).建立糖尿病牙周炎动物模型并按分组用药,分别于1、2、3个月时处死动物,取上颌骨标本进行骨计量学观察.结果:TKR组和AG组牙槽骨嵴高度丧失量和破骨细胞个数均明显小于DP组,成骨细胞个数均明显大于DP组(P＜0.05).结论:补肾方剂和氨基胍均可抑制牙槽骨吸收,增加牙槽骨形成.     

阿仑膦酸钠与雌激素对实验性骨质疏松大鼠种植体骨结合作用的比较研究

目的研究抗骨质疏松药物对骨质疏松状态下种植体骨结合的作用。方法40只12周龄雌性SD大鼠，随机分为四组，每组10只：伪手术组（S组）、卵巢切除组（O组）、OVX＋雌激素组（E组）、OVX＋阿仑膦酸钠组（A组）。S组伪手术12周后，O组、E组、A组卵巢切除12周后双侧股骨进行种植手术。种植术后E组腹腔注射苯甲酸雌二醇；A组阿仑膦酸钠灌胃。各组分别在种植术后6周、12周处死。取右侧胫骨QCT行骨密度测量；左侧带种植体股骨行硬组织切片及骨组织形态计量学测量；右侧带种植体股骨摄X线片和进行力学测试。结果①体重、血清雌二醇、碱性磷酸酶检测S组均与其余三组有统计学差异，且胫骨骨密度检测亦表明大鼠骨质疏松成功建立。②组织学观察：种植术后6周和12周，S组皮质骨区新生骨组织主要为编织骨和成熟的层板骨，并与种植体紧密结合；松质骨区骨小梁密集，粗细不均；种植体表面有一层较厚的新生骨板包绕，仅有少数区域与骨髓腔直接接触。E组和A组组织学改变与S组相似，而O组松质骨区骨小梁稀疏，结合骨板较薄，种植体表面与骨髓腔相通较多。③骨组织形态计量学：O组比S组、E组和A组骨结合率、松质骨区骨量明显下降，结果有统计学意义。E组、A组与S组未有统计学差异。④力学测试结果：A组拔出力虽低于S组，但明显高于O组和E组，与E组相比有统计学意义。结论抗骨质疏松药物均能提高种植体骨结合。雌激素和阿仑膦酸钠治疗在组织学改变相似的情况下，阿仑膦酸钠由于抑制了破骨细胞的活性，其力学性能较雌激素替代治疗组有统计学意义上的提高。     

口腔种植学

补肾方剂对骨质疏松大鼠纯钛种植体骨结合影响的骨计量学研究；逆行性种植体周围炎与根管治疗后邻牙关系的研究；微螺钉种植辅助定位装置的设计及临床应用；管状骨种植骨结合的实验研究；不同基台时种植体支持全瓷单冠的应力分析     

高脂血症大鼠种植体早期骨结合界面的微观动态分析

目的研究高脂血症大鼠种植体早期骨结合界面的微观形态和微观成分的动态变化。方法 Wistar大鼠随机分为实验组和对照组。实验组大鼠饲喂高脂饲料,以建立高脂血症动物模型。12周建模成功后,将种植体植入对照组和实验组大鼠股骨,在植入后的1、3和5 d分别取材,制作硬组织切片,通过光学显微镜和扫描电镜分析种植体早期骨结合界面的微观形态的动态变化,通过X射线能谱仪分析种植体早期骨结合界面的微观成分的动态变化。结果实验组的成骨细胞少于对照组(P<0.05),Ca/P原子个数百分比显著低于对照组(P<0.05),破骨细胞多于对照组(P<0.05),O元素的原子百分比明显高于对照组(P<0.05);由种植体至骨组织Ti元素的原子百分比逐渐减少,实验组和对照组Ti的渗透量无明显差异。结论高脂血症大鼠种植体早期骨结合界面成骨细胞和Ca、P沉积减少,破骨细胞增多,高脂血症抑制种植体早期骨结合。     

PI3K/AKT信号通路在2型糖尿病患者种植体骨结合中作用机制的研究进展

口腔种植治疗目前被认为是缺牙患者的首选治疗方案,但糖尿病仍然是种植治疗的相对禁忌证。糖尿病患者的高血糖环境以及微血管病变等可能会影响成骨细胞及破骨细胞的功能,影响骨代谢,导致种植失败。目前,对于糖尿病影响种植体骨结合的确切机制尚未阐明。PI3K/AKT信号通路在骨组织代谢中起重要作用,可促进成骨细胞的增殖和分化;此外,PI3K/AKT/mTOR也是响应胰岛素信号传导的经典途径。该文分别对PI3K/AKT信号通路在2型糖尿病和种植体骨结合中作用机制的研究进展进行综述,为今后促进糖尿病患者种植体周围骨再生等研究奠定基础。     

补肾方剂对大鼠实验性糖尿病牙周炎的治疗作用

目的观察中药补肾方剂对大鼠实验性糖尿病牙周炎的治疗作用。方法选取纯种雄性SD大鼠随机分为3组,各30只:空白对照组(第1组)、糖尿病牙周炎组(第2组)及中药治疗组(第3组)。第2、3组大鼠按55mg/kg体重腹腔一次性注射链脲佐菌素并结扎上颌磨牙颈部建立糖尿病牙周炎动物模型,第3组用中药补肾方剂治疗,于用中药后1、2、3个月,每组各处死大鼠10只,取上颌骨标本进行骨计量学对比观察。结果第3组用中药后空腹血糖明显降低,附着水平丧失量及牙槽骨嵴高度丧失量均小于第2组,成骨细胞数大于第2组,并随用药时间延长效果更明显,差异有显著性(P<0.05)。结论补肾方剂能有效控制实验大鼠血糖;控制牙周组织炎症,促进牙槽骨形成。     

整合素α5β1和纤维粘连蛋白在Ⅱ型糖尿病大鼠种植体周围骨组织的表达及意义

目的：建立大鼠Ⅱ型糖尿病模型,检测并比较糖尿病大鼠种植体周围骨组织的整合素α5β1和纤维粘连蛋白（fibronectin,FN）表达水平,探讨Ⅱ型糖尿病影响种植体骨结合的可能机制。方法：建立糖尿病大鼠实验动物模型成功后,将48只大鼠随机分为正常种植组（C组）、正常对照组（C0组）、糖尿病种植组（T组）、糖尿病模型组（T0组）。在T组及C组大鼠右侧胫骨近骺端种植纯钛种植体,每组于植入2、4、8周分别处死4只大鼠,采用免疫组化方法检测各组种植体周围骨组织整合素α5β1和FN表达水平。结果：种植术后2周和4周时,T组种植体周围整合素α5β1和FN的表达水平明显高于C组,差异有统计学意义（P〈0.05）。术后8周,T组与C组间整合素α5β1的表达水平接近,而T组FN的表达水平显著高于C组（P〈0.05）。结论：糖尿病可能通过改变种植体周围组织中整合素α5β1及FN表达,削弱了种植体骨结合。     

大豆异黄酮对骨质疏松大鼠种植体骨结合疗效的评价

目的：观察大豆异黄酮对骨质疏松大鼠种植体周围骨以及骨结合强度的影响。方法：选用4月龄雌性SD大鼠40只,用随机区组的方法将其分为假手术组（SHAM,10只）、卵巢切除组（OVX,10只）、卵巢切除＋高剂量大豆异黄酮组（OVX＋SIH,10只）和卵巢切除＋低剂量大豆异黄酮组（OVX＋SIL,10只）共4组。术后8周所有实验动物双侧胫骨干骺端分别植入钛螺纹钉1颗,2个药物干预组使用不同剂量SI药物干预12周。所有实验动物取包含螺纹钉的骨组织块进行生物力学、组织形态定量学检查。结果：与OVX组相比,低剂量和高剂量SI均能有效增加种植体的骨结合（组织形态定量学检测）,并且增加了种植体的最大脱出力,其中高剂量SI组的种植体稳定性与对照组无显著差别（生物力学检测）。结论：本研究结果说明大豆异黄酮有剂量依赖性地改善骨质疏松大鼠钛螺纹钉的骨结合强度的可能性,增强疏松状态下种植体的稳定性。     

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目的探讨辛伐他汀对糖尿病大鼠种植体周围骨组织中骨形态发生蛋白-2(BMP-2)表达的影响及临床意义。方法 2010年5—8月在山西医科大学取成年雄性SD大鼠36只,适应性喂养1周无异常后,随机分为A、B1、B23组,每组12只。A组予腹腔内注射柠檬酸盐缓冲液,B1、B2组按50mg/kg体重剂量予腹腔内注射链尿佐菌素(STZ),建立糖尿病大鼠模型。成模后,在3组大鼠胫骨近骺端种植纯钛种植体。B2组大鼠每日予辛伐他汀5mg/kg体重灌服,A、B1两组大鼠每只每日灌服生理盐水1.5mL。灌胃12周后,处死动物,采用免疫组化方法检测种植体周围骨组织中BMP-2的表达。结果 B2组BMP-2阳性细胞比例明显高于B1组,差异有统计学意义(P<0.01)。结论辛伐他汀能使糖尿病大鼠骨组织BMP-2表达增强,改善骨代谢,有促进种植体骨结合的作用。     

Early cellular responses in cortical bone healing around unloaded titanium implants: an animal study

BACKGROUND: A clear understanding of the early cellular events leading to osseointegration of implants is currently lacking. To gain better insight, titanium implants were inserted in a rabbit model and histologic and histomorphometric analyses were performed at early time points after insertion. METHODS: Thirty-six cylindrical implants were inserted in the tibial diaphysis of six rabbits and left to heal for 1 to 42 days. Samples were processed into paraffin or methylmethacrylate sections, on which the surface of new bone, region of altered nuclear morphology, relative surface of basic multicellular units (BMUs) and blood vessels, and bone-to-implant contact were measured. RESULTS: After coagulum formation, osteoclasts and osteoblasts were observed at the bone surface 1 week after healing. In the preexisting bone, osteocytic lacunae appeared to be devoid of cells. This region of altered nuclear morphology continued to extend for 28 days (P <0.05) after implant insertion. This expansion was accompanied by an invasion of the damaged bone by BMUs that initiated intensive bone remodeling, which reached its maximum after 4 weeks (P <0.05) but was ongoing after 6 weeks of implant insertion. CONCLUSIONS: This study evaluated the early cellular events in cortical bone surrounding titanium implants. The insertion of an implant into bone initiates a series of biologic processes, including the formation of a hematoma, altered nuclear morphology of the osteocytes surrounding the implantation site, intensive bone remodeling, and the formation of new bone, eventually leading to the osseointegration of the implant.     

纳米化种植体表面对糖尿病大鼠种植体骨结合影响研究

目的    观察阳极氧化处理的纳米化种植体表面对糖尿病大鼠种植体骨结合的影响。方法    选择20只12周龄Wisrtar大鼠,通过高脂高糖饲料喂养+腹腔注射小剂量链脲佐菌素的方法建立糖尿病动物模型。尾静脉取血测血糖证实建模成功后,在大鼠双侧股骨远端共植入40枚钛种植体,左侧为对照组（未处理的光滑表面）,右侧为实验组（阳极氧化处理的纳米化表面）,术后12周将大鼠处死取材,进行显微CT扫描、硬组织切片染色观察以及生物力学拔除试验评价种植体骨结合情况。结果    扫描电镜结果显示,经过阳极氧化处理后,钛表面形成了均匀分布的纳米管状结构（管径为15 ~ 80 nm）。种植体植入糖尿病大鼠股骨后12周取材进行观察发现,与对照组相比,实验组种植体周围松质骨骨体积分数（BV/TV）和骨小梁厚度（Tb.Th）均显著升高,骨小梁间隙（Tb.Sp）显著下降,差异均有统计学意义（均P < 0.05）;实验组与对照组的骨结合率分别为41.17% ± 8.71%和30.71% ± 9.18%,最大拔出力分别为（52.36 ± 14.25）N和（40.36 ± 11.51）N,组间差异均有统计学意义（均P < 0.05）。结论        阳极氧化处理的纳米化种植体表面有助于改善糖尿病大鼠的种植体骨结合效果。     

实验性糖尿病牙周炎诱导骨细胞凋亡的初步研究

目的初步探讨糖尿病牙周炎条件下骨细胞的凋亡情况。方法选用6wk雄性SD大鼠62只,随机分为糖尿病牙周炎组（DP,n=22）、牙周炎（P,n=20）以及正常对照组（N,n=20）。采用一次性腹腔注射STZ（55mg/kg）的方法建立大鼠糖尿病模型,注射STZ后1wk检测血糖,血糖≥16.65mmol/L者定为糖尿病大鼠。采用丝线结扎大鼠上颌第二磨牙联合口内接种细菌的方法建立牙周炎模型。动物分别于丝线结扎后3wk和6wk分批处死,进行HE染色和原位细胞凋亡检测。观察指标包括：牙槽骨丧失（ABL）,骨细胞计数,骨细胞凋亡百分率。资料采用单因素方差分析统计学处理。结果丝线结扎后3周和6周,大鼠牙槽骨丧失在N组与P组、N组与DP组、P组与DP组不同,组间两两比较均有统计学意义（P〈0.05）,牙槽骨丧DP组〉P组〉N组。与N组比较,P组和DP组单位面积骨细胞数均减少,与P组比较,DP组单位面积骨细胞数亦显著减少（P〈0.05）。在丝线结扎后3周和6周,糖尿病牙周炎组（DP）骨细胞凋亡百分率均达到牙周炎组（P）的2倍左右。结论糖尿病条件下牙周炎骨丧失明显增加,糖尿病可加强牙周炎条件下牙周组织中骨细胞的凋亡,降低骨细胞的数量。     

Histological evaluation of bone healing using organic bovine bone in combination with platelet-rich plasma (an experimental study on rabbits)

Objectives

This study was carried out to histologically assess the effect of bone grafting materials extracted from bovine origin on the bone healing process either alone or when mixed with autologous platelet-rich plasma which could be used in many procedures of oral and maxillofacial bone and implant reconstructive surgery.

Materials and methods

Sixteen rabbits were used; three intrabony defects in the femur bone of each rabbit were created, one left unfilled for normal healing process and served as control, the second filled with xenogenic graft (Gen-Ox-lyophilized bovine bone organic matrix), and the third filled with(Gen-Ox-lyophilized bovine bone organic matrix) mixed with autologous platelet-rich plasma . Histological examination of the sections was performed after staining with H&E and Van Geison stains. The histomorphometric analysis including counting of bone cells (osteoblasts, osteocytes, and osteoclasts) with performance of osteon diameter and lamellar thickness at the end of the fourth week postoperatively was obtained.

Results

It has been shown that with the use of autologous platelet-rich plasma in combination with the xenogenic bone graft prepared from bovine origin, new bone formation and neovascularization were enhanced significantly when compared with xenogenic graft alone.

Conclusion

The addition of PRP to xenogenic bone substitute in small bone defects of the rabbit femur showed a histomorphometric increase in bone formation (at the fourth week of healing).

Clinical relevance

Platelet concentrate might be used to accelerate the osseointegration of enosseous dental implants.     

骨保护素对去卵巢大鼠中种植体骨整合的影响

目的：探索去卵巢大鼠中骨保护素（osteoprotegerin,OPG）对种植体骨整合的影响。方法大鼠接受双侧卵巢摘除术后12周于胫骨近端植入2颗钛种植钉。将大鼠按每组10只随机分为OPG组与对照组。皮下注射OPG（10 mg/kg）或安慰剂每周3次。8周后收集实验标本进行μCT和组织学以及生物力学分析。结果μCT结果显示,与对照组比较,OPG组中增加了124%的骨体积,167%的骨结合,111%的平均骨小梁数目,92%的平均骨小梁厚度,95%的平均连接密度;降低了64%的平均骨小梁分离度。骨组织形态计量学评价显示OPG组增加160%的骨面积密度和234%骨?种植体接触。生物力学测试提示OPG组种植体的最大推力增加228%。结论全身应用OPG可以改善去卵巢大鼠骨内种植体骨整合和稳定性,其机制可能是通过增加种植体周围的骨量和改善骨小梁微结构。     

Bone formation around titanium implants in the rat tibia: role of insulin

BACKGROUND AND PURPOSE: Clinical and experimental studies show, with few exceptions, that type 1 diabetes mellitus is associated with a delay in bone repair around endosseous implants. The effect of insulin in bone repair/remodeling is not completely understood. The aim of this study was to investigate the course of histological and ultrastructural changes of the osseointegration process under the influence of insulin. MATERIALS AND METHODS: Titanium implants were inserted into the tibiae of male Wistar rats. Animals were divided into three groups: 1) rats with alloxan-induced diabetes; 2) diabetic rats treated with isophane insulin (2 IU/day); and 3) matching controls. Histological and histomorphometric analysis of bone-implant sections were performed 10 and 21 days after implant placement. RESULTS: Relative to control values, rats with alloxan-induced diabetes exhibited a 50% reduction in the area of formed bone (P < 0.001) and in the surface of contact between bone and implant (P < 0.01) 21 days after implant placement. There were no significant differences between groups 10 days after surgery. Values returned to normal levels in diabetic rats after insulin treatment. Presence of chondrocyte-like cells surrounded by a cartilaginouslike matrix in diabetic rats suggests a delay in the process of bone repair. Ultrastructural characteristics of bone-implant interface in diabetic rats treated with insulin resembled those observed in controls. CONCLUSION: The data presented suggest that bone repair around endosseous implants is regulated, at least in part, by insulin. The results imply that the control of the metabolic status of the diabetic patient is essential for a successful osseointegration.