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米诺环素与嗅鞘细胞移植联合治疗对脊髓损伤后炎症和氧化应激的神经保护作用

Neuroprotective Effects of Combined Treatment with Minocycline and Olfactory Ensheathing Cells Transplantation against Inflammation and Oxidative Stress after Spinal Cord Injury.

作者信息

Pourkhodadad Soheila, Oryan S Hahrbanoo, Kaka Gholamreza, Sadraie Seyed Homayoon

机构信息

Department of Animal Physiology, Faculty of Biology, Kharazmi University, Tehran, Iran. Electronic Address:

Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

出版信息

Cell J. 2019 Jul;21(2):220-228. doi: 10.22074/cellj.2019.6126. Epub 2019 Feb 20.

Abstract

OBJECTIVE

Traumatic spinal cord injury (SCI) is considered one of the most devastating injuries leading to neuronal disruption. Olfactory ensheathing cells (OECs) and minocycline have been shown to promote locomotor function after spinal cord injury. In this study, we have tested the efficacy of combined treatment with minocycline and OECs after contusive spinal cord injury.

MATERIALS AND METHODS

In this experimental study, adult female Wistar rats were randomly divided into five groups. Rats received an intraperitoneal injection of minocycline immediately after SCI, and then 24 hours after the injury. Transplantations were performed 7 days after the injury. Functional recovery was evaluated using the Basso, Beattie and Bresnahan scale (BBB). After that, the animals were sacrificed, and T11 segment of the spinal cord was removed after 5 weeks, and then used for histopathological, immunohistochemical, and biochemical assessments. Western blot analysis was applied to determine the protein expression of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL1β) and caspase3.

RESULTS

The results of this study showed that the combination of OECs graft and minocycline reduced the functional deficits and diminished cavitation and astrogliosis in spinal tissue. The analysis of protein expression by western blotting revealed that minocycline treatment along with OECs transplantation further decreased the level of IL-1β, TNF-α, caspase-3, and the oxidative stress as compared with when minocycline or OECs transplantation was used alone.

CONCLUSION

The combinatory treatment with OECs graft and minocycline induced a more effective response to the repair of spinal cord injury, and it is considered a therapeutic potential for the treatment of SCI.

摘要

目的

创伤性脊髓损伤(SCI)被认为是导致神经元破坏的最具毁灭性的损伤之一。嗅鞘细胞(OECs)和米诺环素已被证明可促进脊髓损伤后的运动功能。在本研究中,我们测试了米诺环素与OECs联合治疗对挫伤性脊髓损伤的疗效。

材料与方法

在本实验研究中,成年雌性Wistar大鼠被随机分为五组。大鼠在脊髓损伤后立即腹腔注射米诺环素,然后在损伤后24小时再次注射。损伤7天后进行移植。使用Basso、Beattie和Bresnahan量表(BBB)评估功能恢复情况。之后,处死动物,在5周后取出脊髓的T11节段,然后用于组织病理学、免疫组织化学和生化评估。应用蛋白质印迹分析来测定肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL1β)和半胱天冬酶3的蛋白表达。

结果

本研究结果表明,OECs移植与米诺环素联合使用可减少功能缺陷,并减轻脊髓组织中的空洞形成和星形胶质细胞增生。蛋白质印迹分析蛋白质表达显示,与单独使用米诺环素或OECs移植相比,米诺环素治疗与OECs移植进一步降低了IL-1β、TNF-α、半胱天冬酶-3的水平以及氧化应激。

结论

OECs移植与米诺环素联合治疗对脊髓损伤修复产生了更有效的反应,被认为具有治疗SCI的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a83/6397610/d2b703ae86ad/Cell-J-21-220-g01.jpg

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