Prophylactic role of acetyl-L-carnitine on knee lesions and associated pain in a rat model of osteoarthritis

Prophylactic role of acetyl-L-carnitine on knee lesions and associated pain in a rat model of osteoarthritis
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DOI:
10.1016/j.lfs.2014.04.022
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发表时间:
2014-06-13
期刊:
影响因子:
6.1
通讯作者:
Ghelardini, Carla
Ghelardini, Carla
中科院分区:
医学2区
文献类型:
--
作者:
Bianchi, Enrica;Mannelli, Lorenzo Di Cesare;Ghelardini, Carla

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目的::在本研究中,我们的目的是验证在体内的预防作用的乙酰-L-肉毒碱(ALC)使用建立的膝骨关节炎(OA)的动物模型,其模拟在人类中的OA的病理变化,靶向软骨和引起软骨细胞死亡。在存在或不存在ALC的情况下,通过爪压力和压缩行为测试来测量提交给MIA模型的动物的疼痛。关键发现::来自MIA和ALC共同治疗的大鼠的膝关节的形态学分析显示,归因于组织学发现的总病理学评分在存在ALC的情况下用MIA治疗的大鼠中显著降低。MIA/ALC大鼠膝关节软骨中致病性胶原酶基质金属肽酶13(MMP 13)的OA软骨细胞过度表达可以减少;而II型胶原(COL 2)表达水平可以部分增加到对照值。在我们的实验中,通常与OA相关的疼痛与组织病理学发现的严重程度相关。我们的研究结果表明,有一个地方的ALC作为软骨保护剂在软骨退化,并强烈支持ALC在膝关节骨性关节炎患者的预防和治疗潜力。(C)2014爱思唯尔公司All rights reserved.
Aims: : in the present study, our aim was to validate in vivo the prophylactic role of acetyl-L-carnitine (ALC) using an established knee osteoarthritis (OA) animal model which mimics the pathological changes of OA in humans, targeting cartilage and causing chondrocyte death.Main methods: : animal model was obtained by an intra-articular injection of monosodium iodoacetate (MIA) into rat femorotibial joint space. Pain was measured in animals submitted to MIA model by paw pressure and compression behavioral tests in the presence or absence of ALC.Key findings: : morphological analysis of knee-joint from MIA and ALC co-treated rats showed that the total pathological score attributed to histological findings was dramatically lower in rats treated with MIA in the presence of ALC. OA chondrocyte overexpression of pathogenic collagenase matrix-metallopeptidase-13 (MMP13) could be decreased in knee-cartilage from MIA/ALC rats; whereas type II collagen (COL2) expression level could be partially increased to control value.ALC twice daily treatment was able to attenuate pain in OA rat knee as revealed by mechanical behavioral tests.Significance: : in our experiments, pain that is usually associated with OA, was correlated with the severity of histopathological findings. Our findings show that there is a place for ALC as chondroprotective agents in cartilage degradation and strongly support the prophylactic and therapeutic potentials of ALC in knee-OA patients. (C) 2014 Elsevier Inc. All rights reserved.