Effect of astaxanthin on the apoptosis after spinal cord injury in rats_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

 REN Xiansheng ¹ , DING Wei ² , YANG Xiaoyu ¹

1. Department of Orthopaedics, the Second Hospital of Jilin University, Changchun Jilin, 130041, P.R.China;
2. Department of General Surgery, the Second Hospital of Jilin University, Changchun Jilin, 130041, P.R.China;

Corresponding author：

REN Xiansheng, Email: antren@163.com

Keywords：

Astaxanthin; spinal cord injury; apoptosis; rat

DOI：

10.7507/1002-1892.201712127

Video：

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ObjectiveTo study the effects of astaxanthin on the apoptosis after spinal cord injury in rats.MethodsOne hundred and forty-four healthy adult Sprague Dawley rats were divided into experimental group, control group, and sham group according to the random number table (n=48). In the control group and the experimental group, the modified Allen’s method was used to make the spinal cord injury model; in the sham group, only the lamina was cut without damaging the spinal cord. At immediate after operation, the rats in the experimental group were given intragastric administration of astaxanthin (75 mg/kg) twice a day; and the rats in the control group and the sham group were given equal amount of olive oil by gavage twice a day. BBB score was used to assess the motor function at 1 day and 1, 2, 3, and 4 weeks after operation. The malondialdehyde (MDA) content was determined by the thiobarbituric acid method at 24 hours after operation; and the activity of superoxide dismutase (SOD) was determined by the xanthine oxidase method. Apoptosis index (AI) was determined by TUNEL method at 6, 24, and 48 hours after operation. At 48 hours after operation, the water content of spinal cord was measured by dry-wet weight method, the lesion ratio of spinal cord was calculated, the ultrastructure of the spinal cord was observed by transmission electron microscopy, and ultrastructure scoring was performed using the Kaptanoglu score method.ResultsThe BBB score in the control group and the experimental group was significantly lower than that in the sham group at each postoperative time point (P<0.05); and the BBB score in the experimental group were significantly higher than that in the control group at 1-4 weeks postoperatively (P<0.05). The MDA content in the control group and the experimental group was significantly higher than that in the sham group at 24 hours after operation, and in the experimental group was significantly lower than in the control group (P<0.05). The SOD activity in the control group and the experimental group was significantly lower than that in the sham group, and in the experimental group was significantly higher than in the control group (P<0.05). At each time point postoperatively, the AI in the control group and the experimental group was significantly higher than that in the sham group, and in the experimental group was significantly lower than in the control group (P<0.05). At 48 hours after operation, the water content of spinal cord, the lesion ratio of spinal cord, and the ultrastructure score in the control group and the experimental group were significantly higher than those in the sham group, and in the experimental group were significantly lower than in the control group (P<0.05).ConclusionAstaxanthin can inhibit the lipid peroxidation, reduce the apoptosis, reduce the spinal cord edema, reduce the spinal cord lesion, reduce the histopathological damage after spinal cord injury, and improve the motor function of rats with spinal cord injury, and protect the spinal cord tissue, showing an obvious neuroprotective effect.

Citation： REN Xiansheng, DING Wei, YANG Xiaoyu. Effect of astaxanthin on the apoptosis after spinal cord injury in rats. Chinese Journal of Reparative and Reconstructive Surgery, 2018, 32(5): 548-553. doi: 10.7507/1002-1892.201712127 Copy

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4.	Park JS, Chyun JH, Kim YK, et al. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab (Lond), 2010, 7: 18.
5.	Wu Q, Zhang XS, Wang HD, et al. Astaxanthin activates nuclear factor erythroid-related factor 2 and the antioxidant responsive element (Nrf2-ARE) pathway in the brain after subarachnoid hemorrhage in rats and attenuates early brain injury. Mar Drugs, 2014, 12(12): 6125-6141.
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7.	Wang CM, Cai XL, Wen QP. Astaxanthin reduces isoflurane-induced neuroapoptosis via the PI3K/Akt pathway. Mol Med Rep, 2016, 13(5): 4073-4078.
8.	Zhang M, Cui Z, Cui H, et al. Astaxanthin protects astrocytes against trauma-induced apoptosis through inhibition of NKCC1 expression via the NF-κB signaling pathway. BMC Neurosci, 2017, 18(1): 42.
9.	Pan L, Zhou Y, Li XF, et al. Preventive treatment of astaxanthin provides neuroprotection through suppression of reactive oxygen species and activation of antioxidant defense pathway after stroke in rats. Brain Res Bull, 2017, 130: 211-220.
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11.	Kaptanoglu E, Palaoglu S, Surucu HS, et al. Ultrastructural scoring of graded acute spinal cord injury in the rat. J Neurosurg, 2002, 97(1 Suppl): 49-56.
12.	Li GL, Brodin G, Farooque M, et al. Apoptosis and expression of Bcl-2 after compression trauma to rat spinal cord. J Neuropathol Exp Neurol, 1996, 55(3): 280-289.
13.	Yong C, Amold PM, Zoubine MN, et al. Apoptosis in cellular compartments of rat spinal cord after severe contusion injury. J Neurotrauma,1998, 15(7): 459-472.
14.	Liu XZ, Xu XM, Hu R, et al. Neuronal and glial apoptosis after traumatic spinal cord injury. J Neurosci, 1997, 17(14): 5395-5406.
15.	Crowe MJ, Bresnahan JC, Shuman SL, et al. Apoptosis and delayed degener ation after spinal cord injury in rats and monkeys. Nat Med, 1997, 3(1): 73-76.

1. Fassett RG, Coombes JS. Astaxanthin, oxidative stress, inflammation and cardiovascular disease. Future Cardiol, 2009, 5(4): 333-342.
2. Zhang L, Wang H. Multiple mechanisms of anti-cancer effects exerted by astaxanthin. Mar Drugs, 2015, 13(7): 4310-4330.
3. Liu X, Luo Q, Rakariyatham K, et al. Antioxidation and anti-ageing activities of different stereoisomeric astaxanthin in vitro, and in vivo. J Functional Foods, 2016, 25: 50-61.
4. Park JS, Chyun JH, Kim YK, et al. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab (Lond), 2010, 7: 18.
5. Wu Q, Zhang XS, Wang HD, et al. Astaxanthin activates nuclear factor erythroid-related factor 2 and the antioxidant responsive element (Nrf2-ARE) pathway in the brain after subarachnoid hemorrhage in rats and attenuates early brain injury. Mar Drugs, 2014, 12(12): 6125-6141.
6. Zhang XS, Zhang X, Wu Q, et al. Astaxanthin alleviates early brain injury following subarachnoid hemorrhage in rats: possible involvement of Akt/bad signaling. Mar Drugs, 2014, 12(8): 4291-4310.
7. Wang CM, Cai XL, Wen QP. Astaxanthin reduces isoflurane-induced neuroapoptosis via the PI3K/Akt pathway. Mol Med Rep, 2016, 13(5): 4073-4078.
8. Zhang M, Cui Z, Cui H, et al. Astaxanthin protects astrocytes against trauma-induced apoptosis through inhibition of NKCC1 expression via the NF-κB signaling pathway. BMC Neurosci, 2017, 18(1): 42.
9. Pan L, Zhou Y, Li XF, et al. Preventive treatment of astaxanthin provides neuroprotection through suppression of reactive oxygen species and activation of antioxidant defense pathway after stroke in rats. Brain Res Bull, 2017, 130: 211-220.
10. Zhang XS, Zhang X, Zhou ML, et al. Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage. J Neurosurg, 2014, 121(1): 42-54.
11. Kaptanoglu E, Palaoglu S, Surucu HS, et al. Ultrastructural scoring of graded acute spinal cord injury in the rat. J Neurosurg, 2002, 97(1 Suppl): 49-56.
12. Li GL, Brodin G, Farooque M, et al. Apoptosis and expression of Bcl-2 after compression trauma to rat spinal cord. J Neuropathol Exp Neurol, 1996, 55(3): 280-289.
13. Yong C, Amold PM, Zoubine MN, et al. Apoptosis in cellular compartments of rat spinal cord after severe contusion injury. J Neurotrauma,1998, 15(7): 459-472.
14. Liu XZ, Xu XM, Hu R, et al. Neuronal and glial apoptosis after traumatic spinal cord injury. J Neurosci, 1997, 17(14): 5395-5406.
15. Crowe MJ, Bresnahan JC, Shuman SL, et al. Apoptosis and delayed degener ation after spinal cord injury in rats and monkeys. Nat Med, 1997, 3(1): 73-76.

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