大鼠膝骨关节炎模型血管增生显微CT观察

Micro-CT imaging of angiogenesis in rats with knee osteoarthritis

  • 摘要: 目的 对膝骨性关节炎(osteoarthritis,OA)血管增生状况进行细致的观察,探究大鼠骨关节炎发病机制和血管增生之间的联系。 方法 选择二十只体质量大致为300 g的雌性SD大鼠,并把选取的大鼠进行随机分配,共分为5个小组,每一个小组各4只,其中4个小组作为实验组、另外一组为假手术组。实验组切除大鼠的左膝前交叉韧带和左膝半月板造模,假手术组当中仅打开了大鼠的关节囊,并未对其交叉韧带和半月板实行切除。实验组大鼠在手术之后3周、6周、9周、12周分别进行取材,以上时间段内所获取的材料的位置是大鼠膝关节标本内侧的胫骨平台骨-软骨单元,并且对取材的位置实行进一步的观察和组织评分、Mirco-CT血管形态计量学研究。结果:手术组大鼠在取材3周后,就产生了胫骨平台以及股骨髁的软骨退变,并且距离取材时间越久,大鼠关节炎病变就越重。对各个小组进行大致观察以及组织学评分,计算单位体积内血管体积分数(vascular volume fraction,VVF)以及骨小梁厚度(trabecula thickness,Tb.Th)、骨矿化密度(bone mineral density,BMD)、骨体积分数(bone volume fraction,BVF)。 结果 术后3周关节软骨点状损伤,Tb.Th (0.35±0.21) mm,BMD (29.6±7.2) mg/cm3,BVF (6.1±3.3)%,VVF (0.56±0.24)%;在术后6周时,大鼠关节软骨出现片状退变情况,并且破坏范围变大,Tb.Th (0.24±0.11) mm,BMD (25.7±8.1) mg/cm3,BVF (4.7±1.8)%,VVF (0.71±0.41)%;术后9周关节软骨呈全层缺损,Tb.Th (0.11±0.07) mm,BMD (18.5±10.1) mg/cm3,BVF (3.1±2.1)%,VVF (0.82±0.28)%。术后12周有骨赘形成,Tb.Th (0.05±0.01) mm,BMD (41.3±6.9) mg/cm3,BVF (9.1±1.7)%,VVF (0.17±0.12)%。通过对手术组以及假手术组进行比较可以发现,Tb.Th、BMD、BVF以及VVF有统计学差异(P=0.008)。 结论 血管增生在大鼠骨关节炎的发病机制中仍存在着极大的影响,在大鼠关节炎发生中期,增生微血管数量达到顶峰。

     

    Abstract: Objective To explore the relationship between angiogenesis and knee osteoarthritis (OA) in rats through micro-CT. Methods Twenty female SD rats were divided into five groups randomly, every group had 4 rats, four groups were experimental groups (16) and one group was sham-operated group (4). Rats in experimental group received resection of left knee anterior cruciate ligament and meniscus, rats in sham-operated group with open joint capsules. Rats were sacrificed at 3 weeks, 6 weeks, 9 weeks and 12 weeks in experimental group. Osteochondral composites of medial tibia were sampled sites. The analysis methods included gross observation, mirco-CT vascular morphology metrology and three dimensional reconstruction of angiogenesis. Results Degeneration of cartilage occurred in experimental group after a week. Osteoarthritis became worse over time. Spotted cartilage appeared at 3 weeks after operation, Tb.Th (0.35±0.21) mm, BMD (29.6±7.2) mg/cm3, BVF (6.1±3.3)%, VVF (0.56±0.24)%. Plate shaped cartilage increased at 6 weeks after operation, Tb.Th (0.24±0.11) mm, BMD (25.7±8.1) mg/cm3, BVF (4.7±1.8)%, VVF(0.71±0.41)%. Cartilage defects of full-thickness can be observed at 9 weeks after operation, Tb.Th (0.11±0.07) mm, BMD (18.5±10.1) mg/cm3, BVF (3.1±2.1)%, VVF (0.82±0.28)%. Osteophyte formation in 12 weeks postoperatively. Tb.Th (0.05±0.01) mm, BMD (41.3±6.9) mg/cm3, BVF (9.1±1.7)%, VVF (0.17±0.12)%. Tb.Th, BMD, BVF and VVF were statistically significant in experimental group compared with sham-operated group (P=0.008). Conclusion Angiogenesis is important in the mechanisms of osteoarthritis. Microvascular hyperplasia reaches a peak in the mid-term of the arthritis.

     

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