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药物重新定位:双醋瑞因作为坐骨神经损伤小鼠模型中的一种新治疗方法。

Drug repositioning: diacerein as a new therapeutic approach in a mice model of sciatic nerve injury.

作者信息

Karvat Jhenifer, Andrade Tassiane Emanuelle Servare, Kraus Scheila Iria, Beppler Larissa May, de Jesus Gustavo Dos Santos Catarina, Ferreira Jeane Bachi, da Silva Morgana Duarte

机构信息

Laboratory of Neurobiology of Pain and Inflammation (LANDI), Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, University Campus, Trindade, Florianópolis, SC, 88040-900, Brazil.

Program of Post-Graduation in Neuroscience, Federal University of Santa Catarina, University Campus, Trindade, Florianópolis, SC, 88040-900, Brazil.

出版信息

Pharmacol Rep. 2023 Apr;75(2):358-375. doi: 10.1007/s43440-023-00461-9. Epub 2023 Feb 21.

Abstract

BACKGROUND

Peripheral nerve injuries negatively impact the quality of life of patients, with no effective treatment available that accelerates sensorimotor recovery and promotes functional improvement and pain relief. The aim of this study was to evaluate the effects of diacerein (DIA) in an experimental mice model of sciatic nerve crush.

METHOD

In this study, male Swiss mice were used, randomly separated into six groups as follows: FO (false-operated + vehicle); FO + DIA (false-operated + diacerein 30 mg/kg); SNI (sciatic nerve injury + vehicle); SNI + DIA in doses of 3, 10 and 30 mg/kg (sciatic nerve injury + treatment with diacerein in doses of 3-30 mg/kg). DIA or vehicle was administered 24 h after the surgical procedure, intragastrically, twice a day. The lesion of the right sciatic nerve was generated by crush.

RESULTS

We found that the treatment of animals with DIA accelerated sensorimotor recovery of the animal. In addition, animals in the sciatic nerve injury + vehicle (SNI) group showed hopelessness, anhedonia, and lack of well-being, which were significantly inhibited by DIA treatment. The SNI group showed a reduction in the diameters of nerve fibers, axons, and myelin sheaths, while DIA treatment recovered all these parameters. In addition, the treatment of animals with DIA prevented an increase the levels of interleukin (IL)-1β and a reduction in the levels of the brain-derived growth factor (BDNF).

CONCLUSIONS

Treatment with DIA reduces hypersensitivity and depression like behaviors in animals. Furthermore, DIA promotes functional recovery and regulates IL-1β and BDNF concentrations.

摘要

背景

周围神经损伤会对患者的生活质量产生负面影响,目前尚无有效的治疗方法能加速感觉运动功能恢复、促进功能改善和缓解疼痛。本研究旨在评估双醋瑞因(DIA)在坐骨神经挤压实验小鼠模型中的作用。

方法

本研究使用雄性瑞士小鼠,随机分为以下六组:FO(假手术+赋形剂);FO+DIA(假手术+双醋瑞因30mg/kg);SNI(坐骨神经损伤+赋形剂);SNI+3、10和30mg/kg剂量的DIA(坐骨神经损伤+用3-30mg/kg剂量双醋瑞因治疗)。手术24小时后经胃内给予DIA或赋形剂,每日两次。通过挤压造成右侧坐骨神经损伤。

结果

我们发现用DIA治疗动物可加速其感觉运动功能恢复。此外,坐骨神经损伤+赋形剂(SNI)组的动物表现出绝望、快感缺失和幸福感缺失,而DIA治疗可显著抑制这些表现。SNI组神经纤维、轴突和髓鞘直径减小,而DIA治疗可使所有这些参数恢复。此外,用DIA治疗动物可防止白细胞介素(IL)-1β水平升高和脑源性神经营养因子(BDNF)水平降低。

结论

DIA治疗可减轻动物的超敏反应和类似抑郁的行为。此外,DIA可促进功能恢复并调节IL-1β和BDNF浓度。

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