摘要
背景:研究表明脂质代谢和凝血紊乱以及细胞凋亡与激素性股骨头坏死的发病机制密切相关,而部分研究显示普伐他汀具有降脂、抗凝以及干预骨细胞凋亡的作用。目的:探讨普伐他汀能否降低早期兔激素诱导性股骨头坏死发生的风险,是否可作为兔激素诱导性股骨头坏死的早期靶向干预药物。方法:将60只新西兰雄性兔随机分为3组,模型组和干预组各24只,对照组12只。模型组采用激素联合马血清的方法准备激素性股骨头坏死模型,干预组在模型组的基础上给予普伐他汀治疗,对照组注射等量生理盐水,分别于造模第2、4、6周行血脂、凝血指标检测以及MRI检查,随后处死动物,在光镜下观察组织病理学改变,并计算空骨陷窝率,应用TUNEL法检测骨细胞凋亡,并计算凋亡指数。结果与结论:(1)干预组的大体标本和MRI表现与模型组相比,各周坏死程度相仿,无明显差别;(2)干预组在第2,4周的胆固醇、三酰甘油及低密度脂蛋白水平高于对照组(P<0.05),干预组在第6周的胆固醇、三酰甘油及低密度脂蛋白水平明显低于模型组(P <0.05),但与对照组相比无明显差异(P> 0.05);(3)各组间不同时间点凝血酶原时间及组织纤维溶酶原激活物水平均无显著性差异(P> 0.05);(4)病理组织学显示,干预组骨髓腔内脂肪细胞数、空骨陷窝数较模型组少,骨小梁稀疏程度相对较轻。干预组第2,4周的空骨陷窝率高于对照组(P <0.05),在第6周时,与对照组相比无明显差异(P> 0.05),但显著低于模型组(P <0.05);(5)干预组各时间点的凋亡指数显著高于对照组(P <0.05),但与模型组相比,无显著差异(P> 0.05);(6)结果显示,普伐他汀不能降低早期兔激素诱导性股骨头坏死发生的风险,尚不能作为兔激素诱导性股骨头坏死早期的有效靶向干预药物。
BACKGROUND:Lipid metabolism and coagulation disorders as well as cell apoptosis have been shown to be closely related to the pathogenesis of steroid-induced avascular necrosis of the femoral head(SANFH).Meanwhile,pravastatin has been reported partially to exhibit the effects of lipid-lowering,anticoagulation and interfering the osteocyte apoptosis.OBJECTIVE:To investigate whether pravastatin can reduce the incidence of the early stage of SANFH in rabbits,and whether it can be used as an effective target for early intervention of SIFHN.METHODS:Sixty male New Zealand rabbits were randomly divided into three groups:model group(n=24,early stage of SANFH),intervention group(n=24,early stage of SANFH treated with pravastatin)and control group(n=12,treated with same volume of normal saline).The rabbit model of early stage of SANFH was established by injection of hormone combined with horse serum.All the rabbits were examined for serum lipids and coagulation indicators and underwent MRI examination at 2,4 and 6 weeks after modeling.The rabbits were sacrificed for histopathological observation under light microscope.The ratio of empty lacuna was calculated,apoptosis of osteocytes was determined by TUNEL assay,and apoptotic index was calculated.RESULTS AND CONCLUSION:Compared with the model group,the necrotic degree in the intervention group was similar in the gross specimens and MRI performance,and there was no significant difference.The levels of cholesterol,triglyceride and low density lipoprotein in the intervention group were significantly higher than those in the control group at 2 and 4 weeks after modeling(P<0.05).There was insignificant difference in all above levels between intervention and control groups at 6 weeks after modeling(P>0.05),but the levels in the intervention group were significantly lower than those in the model group(P<0.05).There were no significant differences in the prothrombin time,and tissue plasminogen activator levels among groups at different time points after modeling(P>0.05).Histopathological results revealed that the number of adipocytes and empty lacuna in the bone marrow cavity of the intervention group was less than that in the model group,and the sparse degree of trabecular bone was relatively mild.The ratio of empty lacuna in the intervention group was significantly higher than that in the control group at 2 and 4 weeks after modeling(P<0.05).The ratio of empty lacuna in the intervention group was significantly lower than that in the model group at 6 weeks after modeling(P<0.05),but had no significant difference from that in the control group(P>0.05).The apoptotic index in the intervention group was significantly higher than that in the control group at different time points after modeling(P<0.05),but there was no significant difference between intervention and model groups(P>0.05).To conclude,pravastatin cannot reduce the risk of early SANFH,and cannot be used as an effective target for early intervention of SANFH.
作者
王小龙
韩超前
赵晓娜
赵建民
刘玉
Wang Xiao-long;Han Chao-qian;Zhao Xiao-na;Zhao Jian-min;Liu Yu(Department of Hand and Foot Surgery,the Second Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010030,Inner Mongolia Autonomous Region,China;Department of Pediatrics,the Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,Inner Mongolia Autonomous Region,China;Department of Orthopedics,the Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,Inner Mongolia Autonomous Region,China)
出处
《中国组织工程研究》
CAS
北大核心
2018年第32期5097-5103,共7页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金(81360224)~~
