乳铁蛋白对骨质疏松症大鼠创伤性骨关节炎的疗效

Therapeutic Effect of Lactoferrin on Traumatic Osteoarthritis Preceded by Osteoporosis

目的:研究乳铁蛋白(LF)对患有骨关节炎的骨质疏松大鼠的软骨及软骨下骨的作用。方法:将40只雌性SD大鼠随机分为4组:骨关节炎组,骨关节炎乳铁蛋白治疗组,关节炎及骨质疏松组,骨关节炎及骨质疏松乳铁蛋白治疗组,每组各10只,双侧卵巢切除或假手术,12周后手术建立膝关节创伤性骨关节炎模型,根据分组不同给予LF(85mg/kg·d-1)或安慰剂。8周后取大鼠胫骨近端进行组织学检测、micro-CT、免疫组织化学染色、RTPCR、western blot评价。结果:LF的作用主要体现在OVX大鼠中,与对照组相比,LF干预组软骨下骨组织BV/TV增加了30.2%,Tb.Th增加了33.7%,Tb.Sp减少了50.1%;LF干预还降低了MMP-13和TRAP的mRNA及蛋白表达,增加了Runx2的mRNA及蛋白表达增加。结论:乳铁蛋白可以缓解OVX大鼠的创伤性骨关节炎,这种效果可能与LF对软骨下骨的作用间接相关,或者与LF降低MMP-13和TRAP表达的作用直接相关。

Objective：To evaluate whether Lactoferrin（LF）has a therapeutic effect on cartilage and subchondral bone in osteoporotic（OP）rats with osteoarthritis（OA）.Methods：Forty female Sprague Dawley rats were stratified into four groups with 10 animals per group：OA,OA＋LF,OP＋OA,OP＋OA＋LF.OA was induced 12 weeks after bilateral ovariectomy（OVX）or sham operation.LF dissolved in 2ml 0.9% normal saline was administered by oral gavages at a dose of 85mg/kg/d,starting from the first day after the induction of OA.After 8-week treatment,the proximal tibia was harvested for histology,micro-computed tomography（micro-CT）,immunohistochemical staining,real-time polymerase chain reaction,as well as western blot evaluation.Results：Therapeutic effect of LF was mainly observed in OVX rats,which increased BV/TV by 30.2%,the Tb.Th by 33.7%,and decreased Tb.Sp by 50.1%in micro-CT analysis of the subchondral bone.LF treatment also decreased the mRNA and protein expression of matrix metalloproteinase-13（MMP-13）and tartrate-resistant acid phosphatase（TRAP）,as well as increasing the mRNA and protein expression of runt-related transcription factor 2（Runx2）in OVX rats.Conclusion：LF treatment reduced traumatic osteoarthritis in OVX rats,which was possibly related to the beneficial effect of LF on subchondral bone tissue indirectly,or direct effect on cartilage by decreasing the expression of MMP-13 and TRAP.