中药淫羊藿苷预防人工髋关节无菌性松动实验研究
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摘要
人工髋关节无菌性松动是人工髋关节置换术的主要并发症,它严重阻碍了人工关节的推广应用。目前,随着该项技术的不断普及和人工髋关节使用年限的延长,因人工髋关节无菌性松动而需做人工髋关节翻修手术的病例将逐渐增多。由于翻修术的疗效低于初次手术,而且手术创伤大、价格昂贵,如何有效地防治人工髋关节无菌性松动这一晚期并发症已成为骨科领域的一个重要课题。
人工髋关节置换术后由于长期磨损而产生的大量磨损微粒(包括聚乙烯微粒、骨水泥微粒和金属微粒),磨损微粒刺激假体周围的单核巨噬细胞分泌多种溶骨性因子(主要包括TNF-α,IL-1,IL-6,PGE_2和胶原酶等),溶骨性因子进而激活假体周围的破骨细胞,从而产生假体周围骨吸收和骨溶解,最终导致人工髋关节无菌性松动。我们在研究了人工髋关节无菌性松动发病机制的基础上,提出应用中药淫羊藿苷防治人工髋关节无菌性松动的设想,探讨淫羊藿苷防治松动的机理,并进行了部分实验研究。
目的:探讨中药淫羊藿苷对微粒刺激破骨细胞骨吸收功能的影响;建立兔股骨头假体和聚乙烯颗粒刺激下导致假体松动的动物模型;探讨人工髋关节置换术后假体周围组织的病理变化及如何应用淫羊藿苷防治磨损颗粒引起的骨溶解。
方法:1、建立破骨细胞体外培养体系,将破骨细胞骨片、聚乙烯微粒与淫羊藿苷共同培养,并设立对照组。观察骨吸收陷窝的数目和面积。2、磨损颗粒诱导假体松动的动物模型的实验研究。3、淫羊藿苷对人工髋关节无菌性松动的影响。
结果:1、聚乙烯微粒能明显增强破骨细胞的骨吸收功能,而淫羊藿苷能明显抑制微粒介导的破骨细胞的骨吸收功能。2、骨密度仪检测下实验组兔股骨头模拟假体周围的间隙较对照组大,骨密度值亦明显低,说明实验组兔股骨头模拟假体周围有溶骨现象,临近模拟假体的骨组织密度较对照组降低。3、骨密度仪扫描显示甲组试验组的兔股骨头模拟假体四周模糊,与骨组织之间距离近似零,骨密度值较高,乙组和丙组兔股骨头模拟假体四周清晰,与骨组织之间空隙较对照组明显大,骨密度值明显较低。大体观察和镜下显示,乙、丙组模拟假体旁可见骨组织坏死、骨陷窝空虚、骨纹理模糊、边缘不光整、周围纤维组织增生。甲组模拟假体周围有新生骨形成。乙、丙组模拟假体隧道边缘产生一层纤维结缔组织界膜。
结论:淫羊藿苷对聚乙烯微粒介导的破骨细胞的骨吸收作用有明显得抑制作用。钛合金和聚乙烯颗粒能够刺激组织细胞分泌TNF-α、IL-1和IL-6等溶骨性因子。这些溶骨性因子既激活破骨细胞、诱导破骨细胞的增殖,促使假体周围的骨溶解和骨吸收,而且促进假体周围的组织的纤维化,最终导致假体松动。淫羊藿苷能明显抑制磨损微粒介导的破骨细胞的活性,抑制磨损微粒介导TNF-α,IL-1和IL-6的分泌;淫羊藿苷局部直接给药能够防治由磨损颗粒引起骨溶解、骨坏死,从而预防由磨损颗粒导致的人工髋关节无菌性松动。临床上淫羊藿与淫羊藿复方制剂药物能明显缓解病人的疼痛等症状,使骨密度增高,假体周围的骨密度增加了。我们相信,随着淫羊藿苷作用机理的不断阐明和临床实验的进展,淫羊藿苷有望成为防治人工髋关节无菌性松动的有效药物。
The Effect of Icariins on the Prevention and Therapy of Aseptic Loosening after THA
Artificial hip joint is aseptic loosening of total hip replacement the major complications,it has seriously hindered the promotion of artificial joints.At present, as the technology and the ever-growing popularity of artificial hip joints to extend the life span because of aseptic loosening and hip to be done hip surgery renovation of the cases will be gradually increased.The renovation of the effect below the initial surgery,and surgical trauma,which is very expensive,and how to effectively control artificial hip aseptic loosening of this advanced orthopedic complications have become an important topic areas.
Artificial hip replacement surgery because of long-term wear and the wear particles generated a large number(including polyethylene particles,bone cement particles and metal particles),the wear particles around,the prosthesis to stimulate monocyte macrophages secreting a variety of osteolytic factor(including TNF-α, IL-1,IL-6,PGE2 and collagenase,etc.),thus activating factor osteolytic prosthesis around the osteoclasts,thereby creating phantom surrounding bone resorption and bone dissolution,which eventually led to artificial Hip aseptic loosening.We studied artificial hip pathogenesis of aseptic loosening proposed on the basis of application of Chinese medicine icariin hip aseptic loosening the idea of icariin loose control mechanism,and some experimental study.
Objective:To explore the effects of particulate icariin stimulate osteoclast resorption the impact of the establishment of rabbit femoral head prosthesis and stimulation of polyethylene particles resulting prosthesis loosening of the animal model;of artificial hip replacement prosthesis after around the pathological changes and the application of icariin of wear particles from osteolysis.
Method:1.,the establishment of osteoclasts in vitro system,osteoclast bone,and polyethylene particles icariin common culture,and the establishment of the control group.Observation of bone resorption lacunae in the number and size.2,wear particles induced prosthetic loosening of the experimental animal model study.3, icariin right hip aseptic loosening effects.
Results:1,polyethylene particles can significantly enhance osteoclastic bone resorption,and icariin could significantly inhibit particle-mediated osteoclast resorption.2,measured bone mineral density in the experimental group under simulated rabbit femoral head prosthesis around the gap compared with the control group,also significantly lower bone mineral density values,the simulation of the experimental group of rabbit femoral head prosthesis osteolysis around the phenomenon,near the phantom simulation bone density than the control group decreased.3,BMD Group A scan revealed that the experimental group simulated rabbit femoral head prosthesis around vague,and the distance between the bone tissue similar to zero,the higher value of bone mineral density;Group B and Group C simulation rabbit femoral head prosthesis around clear,and the gap between the bone tissue in the control group,bone mineral density was significantly lower.Gross observation and under,B,C next to that simulated phantom bone tissue necrosis,bone lacunae emptiness,bone fuzzy texture,not just the edge the whole,the surrounding fibrous tissue hyperplasia.Group A simulation phantom around the new bone formation.B and C of the tunnel at the edge simulation produced a fibrous connective tissue membrane.
Conclusion:icariin polyethylene particles on the osteoclast-mediated bone resorption cells obvious role in the inhibition.Titanium and polyethylene particles can stimulate cell secretion of TNF-α,IL-1 and IL-6 and other osteolytic factor.These factors both osteolytic osteoclast activation induced osteoclast cell proliferation, prompted prosthesis and the surrounding bone resorption dissolved,and the promotion of bogus organizations around fibrosis,which eventually led to prosthetic loosening.Icariin could inhibit the wear debris mediated osteoclast activity,wear debris mediated inhibition of TNF-α,IL-1 and IL-6 secretion;icariin local control from direct administration of wear particles can cause bone dissolved,bone necrosis, which led to the prevention of wear particles from the hip aseptic loosening. Epimedium and clinical drug compound preparation Epimedium can significantly alleviate the patient's pain and other symptoms,increased bone mineral density,bone mineral density around the prosthesis has increased.We believe that as the role of icariin articulate and the continuous progress in clinical trials,is expected to become icariin of artificial hip aseptic loosening of effective drug.
人工髋关节置换术后由于长期磨损而产生的大量磨损微粒(包括聚乙烯微粒、骨水泥微粒和金属微粒),磨损微粒刺激假体周围的单核巨噬细胞分泌多种溶骨性因子(主要包括TNF-α,IL-1,IL-6,PGE_2和胶原酶等),溶骨性因子进而激活假体周围的破骨细胞,从而产生假体周围骨吸收和骨溶解,最终导致人工髋关节无菌性松动。我们在研究了人工髋关节无菌性松动发病机制的基础上,提出应用中药淫羊藿苷防治人工髋关节无菌性松动的设想,探讨淫羊藿苷防治松动的机理,并进行了部分实验研究。
目的:探讨中药淫羊藿苷对微粒刺激破骨细胞骨吸收功能的影响;建立兔股骨头假体和聚乙烯颗粒刺激下导致假体松动的动物模型;探讨人工髋关节置换术后假体周围组织的病理变化及如何应用淫羊藿苷防治磨损颗粒引起的骨溶解。
方法:1、建立破骨细胞体外培养体系,将破骨细胞骨片、聚乙烯微粒与淫羊藿苷共同培养,并设立对照组。观察骨吸收陷窝的数目和面积。2、磨损颗粒诱导假体松动的动物模型的实验研究。3、淫羊藿苷对人工髋关节无菌性松动的影响。
结果:1、聚乙烯微粒能明显增强破骨细胞的骨吸收功能,而淫羊藿苷能明显抑制微粒介导的破骨细胞的骨吸收功能。2、骨密度仪检测下实验组兔股骨头模拟假体周围的间隙较对照组大,骨密度值亦明显低,说明实验组兔股骨头模拟假体周围有溶骨现象,临近模拟假体的骨组织密度较对照组降低。3、骨密度仪扫描显示甲组试验组的兔股骨头模拟假体四周模糊,与骨组织之间距离近似零,骨密度值较高,乙组和丙组兔股骨头模拟假体四周清晰,与骨组织之间空隙较对照组明显大,骨密度值明显较低。大体观察和镜下显示,乙、丙组模拟假体旁可见骨组织坏死、骨陷窝空虚、骨纹理模糊、边缘不光整、周围纤维组织增生。甲组模拟假体周围有新生骨形成。乙、丙组模拟假体隧道边缘产生一层纤维结缔组织界膜。
结论:淫羊藿苷对聚乙烯微粒介导的破骨细胞的骨吸收作用有明显得抑制作用。钛合金和聚乙烯颗粒能够刺激组织细胞分泌TNF-α、IL-1和IL-6等溶骨性因子。这些溶骨性因子既激活破骨细胞、诱导破骨细胞的增殖,促使假体周围的骨溶解和骨吸收,而且促进假体周围的组织的纤维化,最终导致假体松动。淫羊藿苷能明显抑制磨损微粒介导的破骨细胞的活性,抑制磨损微粒介导TNF-α,IL-1和IL-6的分泌;淫羊藿苷局部直接给药能够防治由磨损颗粒引起骨溶解、骨坏死,从而预防由磨损颗粒导致的人工髋关节无菌性松动。临床上淫羊藿与淫羊藿复方制剂药物能明显缓解病人的疼痛等症状,使骨密度增高,假体周围的骨密度增加了。我们相信,随着淫羊藿苷作用机理的不断阐明和临床实验的进展,淫羊藿苷有望成为防治人工髋关节无菌性松动的有效药物。
The Effect of Icariins on the Prevention and Therapy of Aseptic Loosening after THA
Artificial hip joint is aseptic loosening of total hip replacement the major complications,it has seriously hindered the promotion of artificial joints.At present, as the technology and the ever-growing popularity of artificial hip joints to extend the life span because of aseptic loosening and hip to be done hip surgery renovation of the cases will be gradually increased.The renovation of the effect below the initial surgery,and surgical trauma,which is very expensive,and how to effectively control artificial hip aseptic loosening of this advanced orthopedic complications have become an important topic areas.
Artificial hip replacement surgery because of long-term wear and the wear particles generated a large number(including polyethylene particles,bone cement particles and metal particles),the wear particles around,the prosthesis to stimulate monocyte macrophages secreting a variety of osteolytic factor(including TNF-α, IL-1,IL-6,PGE2 and collagenase,etc.),thus activating factor osteolytic prosthesis around the osteoclasts,thereby creating phantom surrounding bone resorption and bone dissolution,which eventually led to artificial Hip aseptic loosening.We studied artificial hip pathogenesis of aseptic loosening proposed on the basis of application of Chinese medicine icariin hip aseptic loosening the idea of icariin loose control mechanism,and some experimental study.
Objective:To explore the effects of particulate icariin stimulate osteoclast resorption the impact of the establishment of rabbit femoral head prosthesis and stimulation of polyethylene particles resulting prosthesis loosening of the animal model;of artificial hip replacement prosthesis after around the pathological changes and the application of icariin of wear particles from osteolysis.
Method:1.,the establishment of osteoclasts in vitro system,osteoclast bone,and polyethylene particles icariin common culture,and the establishment of the control group.Observation of bone resorption lacunae in the number and size.2,wear particles induced prosthetic loosening of the experimental animal model study.3, icariin right hip aseptic loosening effects.
Results:1,polyethylene particles can significantly enhance osteoclastic bone resorption,and icariin could significantly inhibit particle-mediated osteoclast resorption.2,measured bone mineral density in the experimental group under simulated rabbit femoral head prosthesis around the gap compared with the control group,also significantly lower bone mineral density values,the simulation of the experimental group of rabbit femoral head prosthesis osteolysis around the phenomenon,near the phantom simulation bone density than the control group decreased.3,BMD Group A scan revealed that the experimental group simulated rabbit femoral head prosthesis around vague,and the distance between the bone tissue similar to zero,the higher value of bone mineral density;Group B and Group C simulation rabbit femoral head prosthesis around clear,and the gap between the bone tissue in the control group,bone mineral density was significantly lower.Gross observation and under,B,C next to that simulated phantom bone tissue necrosis,bone lacunae emptiness,bone fuzzy texture,not just the edge the whole,the surrounding fibrous tissue hyperplasia.Group A simulation phantom around the new bone formation.B and C of the tunnel at the edge simulation produced a fibrous connective tissue membrane.
Conclusion:icariin polyethylene particles on the osteoclast-mediated bone resorption cells obvious role in the inhibition.Titanium and polyethylene particles can stimulate cell secretion of TNF-α,IL-1 and IL-6 and other osteolytic factor.These factors both osteolytic osteoclast activation induced osteoclast cell proliferation, prompted prosthesis and the surrounding bone resorption dissolved,and the promotion of bogus organizations around fibrosis,which eventually led to prosthetic loosening.Icariin could inhibit the wear debris mediated osteoclast activity,wear debris mediated inhibition of TNF-α,IL-1 and IL-6 secretion;icariin local control from direct administration of wear particles can cause bone dissolved,bone necrosis, which led to the prevention of wear particles from the hip aseptic loosening. Epimedium and clinical drug compound preparation Epimedium can significantly alleviate the patient's pain and other symptoms,increased bone mineral density,bone mineral density around the prosthesis has increased.We believe that as the role of icariin articulate and the continuous progress in clinical trials,is expected to become icariin of artificial hip aseptic loosening of effective drug.
引文
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