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首页> 外文期刊>Orthopaedic Journal of Sports Medicine >The beneficial effect of intra-articular injection of losartan on the microfracture mediated cartilage repair is dose dependent
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The beneficial effect of intra-articular injection of losartan on the microfracture mediated cartilage repair is dose dependent

机译：关节内注射氯沙坦对微磨术介导的软骨修复的有益效果是剂量依赖性的

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Objectives: 1. To determine the dosage and beneficial effects of intra-articular injection of losartan on microfracture-mediated cartilage repair and normal cartilage homeostasis. Methods: Rabbits were divided into 5 groups (n=6): a microfracture group (MFX) and 4 different losartan treatment cohorts received varying dosages of IA losartan (0.1,1,10 and 100 mg/knee). An osteochondral defect (5mm) was created in the trochlear groove cartilage and 5 microfracture perforations were performed in the osteochondral defect. Both injured and contralateral knee joints were injected with losartan IA at days 0,14 and 28 after surgery. Rabbits were sacrificed at 6 weeks after surgery for analysis including gross observation, micro computed tomography, histology analysis and reverse transcription quantitative PCR. Results: Micro computed tomography analysis and gross observation demonstrated comparable subchondral bone healing and hyaline-like appearing cartilage morphology in the 0.1, 1 and 10mg/knee losartan IA injection groups relative to the MFX group. Conversely, IA injection of losartan at 100mg/knee dosage showed neither bony defect healing nor cartilage repair. Histology revealed higher O’Driscoll scores and hyaline cartilage regeneration in the 1mg/knee cohort when compared to the MFX group. In contrast,100mg/knee losartan showed the lowest histology score and no cartilage repair. IA injection of losartan at the doses of 0.1,1 and 10mg/knee did not cause adverse effects on uninjured cartilage while 100mg/knee dose induced cartilage damage. Q-PCR results showed down-regulation of the TGFβ signaling pathway after losartan injection. Conclusions: Intra-articular injection of losartan at the dose 1mg/knee was most effective for enhancement of microfracture-mediated cartilage repair without adversely affecting uninjured cartilage. Conversely, high dose (100mg/knee) IA injection of losartan inhibited cartilage repair in osteochondral defect and was chondrotoxic to normal articular cartilage.
机译：目的：1。确定氯沙坦内胞内注射氯沙兰介导的软骨修复和正常软骨稳态的剂量和有益效果。方法：将兔分为5组（n = 6）：微折衷基团（MFX）和4种不同的氯沙坦治疗队列接受了Ia氯沙坦（0.1,1,10和100mg / knee）的不同剂量。在Trochlear槽软骨中产生骨缺损（5mm），在骨质色神经缺陷中进行5微折断穿孔。受伤和对侧膝关节均在手术后的第0,14和28天注射氯沙坦Ia。在手术后6周内牺牲了兔子，用于分析，包括总观察，微计算机断层扫描，组织学分析和逆转录量化PCR。结果：微计算机断层扫描分析和总观察表明，相对于MFX组的0.1,1和10mg /膝关节Ia注射组的软骨形态表现出可比的子骨髓愈合和透明化的样品。相反，IA在100mg /膝盖剂量下注射氯沙坦既不显示骨缺损愈合和软骨修复。与MFX组相比，组织学揭示了1mg /膝队队列中的o'driscoll分数和透明软骨再生。相比之下，100mg / knee洛萨沙展示了最低的组织学评分，没有软骨修复。 IA注射0.1,1和10mg / knee的剂量的氯沙坦对未加注的软骨产生不利影响，而100mg /膝关节剂量诱导软骨损伤。 Q-PCR结果显示氯沙坦注射后TGFβ信号通路的下调。结论：在剂量1mg / knee时，关节内注射氯沙坦，对微裂缝介导的软骨修复的增强最有效，而不会对未加注的软骨产生不利影响。相反，高剂量（100mg / knee）Ia注射氯沙坦抑制骨质色神经缺陷的软骨修复，并且是常规关节软骨的软糖毒性。

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