Adah Felix, Benghuzzi Hamed A, Tucci Michelle A
University of Mississippi Medical Center, Jackson.
Biomed Sci Instrum. 2014;50:54-61.
This study investigated the effects of dual delivery of statin and vancomycin on angiogenesis during the healing process of a femoral defect injury using tricalcium phosphate lysine (TCPL) delivery system in an animal model. The experimental design consisted of 14 rats divided into the following three groups: Group I animals (n=5) served as the intact control without treatment. Group II animals (n=5) were subjected to a surgically induced defect (2 mm, midshaft of the right femur) and implanted (IM) with TCPL capsules loaded with vancomycin (20mg) (TCPL-AB). Group III animals (n=4) were operated on in a similar fashion as Group II, and subsequently implanted with TCPL capsules loaded vancomycin (20 mg) plus statin (5 mg). The animals were euthanized at 30 days post-implantation using overdose of isoflourane. The right femurs were then harvested in addition to the vital organs, the reproductive organs, and sample of the adjacent skeletal muscles. The hard and soft tissues were evaluated histopathologically by following laboratory standard techniques. The results of this study indicated that statin plus vancomycin treated animals had increased angiogenetic activities with many blood vessels compared to the sham group and the animals also healed in a greater magnitude than the sham group (independent evaluators (p<0.001)). Histomorphometric analysis demonstrated that exposure to sustained delivery of statin resulted in increased blood vessels. It appeared there is a direct correlation of the increased angiogenesis and the increased bone formation in the statin group and this may be one of the mechanisms with which statin form bone. In conclusion, data obtained from this study demonstrated that sustained delivery of statin by TCPL resulted in a remarkable increase in angiogenic and osteogenic activities during the healing process of a femoral defect.
本研究在动物模型中,使用磷酸三钙赖氨酸(TCPL)递送系统,研究了他汀类药物和万古霉素双重递送对股骨缺损损伤愈合过程中血管生成的影响。实验设计包括将14只大鼠分为以下三组:第一组动物(n = 5)作为未经治疗的完整对照组。第二组动物(n = 5)接受手术诱导的缺损(2毫米,右股骨中段),并植入装载万古霉素(20毫克)的TCPL胶囊(TCPL-AB)。第三组动物(n = 4)以与第二组相似的方式进行手术,随后植入装载万古霉素(20毫克)加他汀类药物(5毫克)的TCPL胶囊。在植入后30天,使用过量异氟烷对动物实施安乐死。然后除了重要器官、生殖器官和相邻骨骼肌样本外,还采集了右股骨。按照实验室标准技术对硬组织和软组织进行组织病理学评估。本研究结果表明,与假手术组相比,接受他汀类药物加万古霉素治疗的动物血管生成活性增加,血管数量增多,并且这些动物的愈合程度也高于假手术组(独立评估者,p<0.001)。组织形态计量学分析表明,持续递送他汀类药物会导致血管增多。他汀类药物组中血管生成增加与骨形成增加之间似乎存在直接关联,这可能是他汀类药物形成骨的机制之一。总之,本研究获得的数据表明,TCPL持续递送他汀类药物在股骨缺损愈合过程中导致血管生成和成骨活性显著增加。