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超声引导下肌腱内注射贝伐单抗加速肌腱愈合的初步临床前研究:一种在鼠模型上的研究。

Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: first pre-clinical study on a murine model.

机构信息

Service de Radiologie, Hôpital universitaire Bichat, Paris, France; Inserm U698, Hôpital universitaire Bichat, Paris, France; Université de Médecine Paris Diderot, France.

出版信息

Eur J Radiol. 2013 Dec;82(12):e823-8. doi: 10.1016/j.ejrad.2013.06.012. Epub 2013 Sep 12.

Abstract

PURPOSE

Tendinopathy shows early disorganized collagen fibers with neo-angiogenesis on histology. Peri-tendinous injection of corticosteroid is the commonly accepted strategy despite the abscence of inflammation in tendinosis. The aim of our study was to assess the potential of intratendinous injection of an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model of patellar and Achilles tendinopathy, and to evaluate its local toxicity.

MATERIALS AND METHOD

Forty rats (160 patellar and Achilles tendons) were used for this study. We induced tendinosis (T+) in 80 tendons by injecting under ultrasonography (US) guidance Collagenase 1(®) (day 0 = D0, patellar = 40 and Achilles = 40). Clinical examination and tendon US were performed at D3, immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using clinical, US and histology, and comparison between the 2 groups were performed. To study AA toxicity we compared the 80 remaining normal tendons (T-) after injecting AA in 40 (AAT-).

RESULTS

All AAT+ showed a better joint mobilization compared to PST+ at D6 (p = 0.004) with thinner US tendon diameters (p<0.004), and less disorganized collagen fibers and neovessels on histology (p<0.05). There was no difference at D13 regarding clinical status, US tendon diameter and histology (p>0.05). Comparison between AAT- and T- showed no AA toxicity on tendon (p = 0.18).

CONCLUSION

Our study suggests that high dose mono-injection of AA in tendinosis, early after the beginning of the disease, accelerates tendon's healing, with no local toxicity.

摘要

目的

组织病理学显示,肌腱病早期出现胶原纤维排列紊乱伴新生血管形成。尽管肌腱病中没有炎症,但皮质类固醇的腱周注射仍然是被广泛接受的治疗策略。本研究的目的是评估在兔膝腱和跟腱肌腱病模型中,向肌腱内注射抗血管生成药物(贝伐单抗,AA)治疗肌腱病的潜力,并评估其局部毒性。

材料和方法

本研究共使用了 40 只大鼠(160 个膝腱和跟腱)。我们通过超声引导下注射胶原酶 1(®)(第 0 天=D0,膝腱=40 个,跟腱=40 个)在 80 个肌腱中诱导肌腱病(T+)。在 D3 时进行临床检查和肌腱超声检查,然后立即进行 AA(AAT+,n=40)或生理血清(PST+,n=40,对照组)的超声引导下肌腱内注射。在 D6 和 D13 时进行临床、超声和组织学随访,并对两组进行比较。为了研究 AA 的毒性,我们比较了在 40 个正常肌腱(T-)中注射 AA 后的 80 个剩余正常肌腱(AAT-)。

结果

所有 AAT+在 D6 时与 PST+相比,关节活动度更好(p=0.004),超声肌腱直径更细(p<0.004),组织学上胶原纤维和新生血管排列更规则(p<0.05)。在 D13 时,临床状况、超声肌腱直径和组织学均无差异(p>0.05)。AAT-和 T-之间的比较表明,肌腱内注射 AA 没有局部毒性(p=0.18)。

结论

本研究表明,在疾病早期,高剂量单次注射 AA 可加速肌腱愈合,且无局部毒性。

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