CHOLESTEROL PRODUCTION INHIBITOR (STATIN) INCREASED ANGIOGENESIS IN SURGICALLY CREATED FEMORAL DEFECT IN AN ANIMAL MODEL

摘要

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.