Inhibition of peroxisome proliferator activated receptor gamma agonist on autophagy-associated proteins in rats after spinal cord injuries

doi:10.3877/cma.j.issn.1674-6880.2019.04.002

Abstract

Abstract:

Objective

To investigate the inhibitory effect of peroxisome proliferator activated receptor gamma (PPARγ) agonist on autophagy-associated proteins in rats after spinal cord injuries.

Methods

A total of 60 rats were randomly divided into the sham operation group, model group, agonist group and inhibitor group, with 15 rats in each group. The spinal cord was exposed by laminectomy and the model of spinal cord injuries was established by an epidural compression of the spinal cord with a sterile artery clip at the T6-T7 segment. Rats in the sham operation group only performed laminectomy. Rats in the agonist and inhibitor groups were intraperitoneally injected with rosiglitazone and GW9662 (2 mg/kg, once every 2 hours) respectively after spinal cord injuries and rats in the sham operation and model groups were given an equal dose of isotonic NaCl solution by intraperitoneal injection. The hindlimb motor function was assessed on 3, 5, 7, 14, 21, and 28 d after spinal cord injuries using the Tarlov's scoring method. The expressions of LC3-Ⅱ/LC3-Ⅰ, beclin-1 and cathepsin D were detected by Western-blotting and the PPARγ mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR).

Results

The Tarlov's scores at different time points among 4 groups were significantly different (F = 25.674, P < 0.001). Compared with the sham operation group, the Tarlov's scores in the other 3 groups decreased obviously on 3, 5, 7, 14, 21, and 28 d after spinal cord injuries (all P < 0.05); the Tarlov's scores in the agonist group were much higher than those in the model and inhibitor groups (all P < 0.05). The expressions of LC3-Ⅱ/LC3-Ⅰ, beclin-1, cathepsin D and PPARγ mRNA on 3 d after spinal cord injuries were significantly different among 4 groups as well (F = 238.213, 28.268, 172.563, 32.492; all P < 0.001). The expressions of LC3-Ⅱ/LC3-Ⅰ, beclin-1, cathepsin D and PPARγ mRNA in the sham operation group were much lower than those in the other 3 groups (all P < 0.05). Compared with the agonist group, the expressions of LC3-Ⅱ/LC3-Ⅰ and PPARγ mRNA decreased, and the expressions of beclin-1 and cathepsin D increased in the model and inhibitor groups (all P < 0.05).

Conclusion

The PPARγ agonist can promote the recovery of neurological function in rats after spinal cord injuries by down-regulating the expressions of autophagy-associated proteins.

Key words: PPAR gamma, Spinal cord injuries, Autophagy, Rats

Xiaohui Yang, Qin Zhang, Honglin Yu, Guohui Xie. Inhibition of peroxisome proliferator activated receptor gamma agonist on autophagy-associated proteins in rats after spinal cord injuries[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2019, 12(04): 223-228.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhwzzyxzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-6880.2019.04.002

https://zhwzzyxzz.cma-cmc.com.cn/EN/Y2019/V12/I04/223

Figures/Tables 7

References 22

1	Cheng P, Kuang F, Ju G. Aescin reduces oxidative stress and provides neuroprotection in experimental traumatic spinal cord injury[J]. Free Radic Biol Med, 2016 (99): 405-417.
2	Hihi AK, Michalik L, Wahli W. PPARs: transcriptional effectors of fatty acids and their derivatives[J]. Cell Mol Life Sci, 2002, 59 (5): 790-798.
3	Wu XJ, Sun XH, Wang SW, et al. Mifepristone alleviates cerebral ischemia-reperfusion injury in rats by stimulating PPAR γ[J]. Eur Rev Med Pharmacol Sci, 2018, 22 (17): 5688-5696.
4	Sun W, Zheng K, Liu B, et al. Neuroprotective potential of gentongping in rat model of cervical spondylotic radiculopathy targeting PPAR-γ pathway[J]. J Immunol Res, 2017: 9152960.
5	Liu H, Rose ME, Culver S, et al. Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats[J]. Biochem Biophys Res Commun, 2016, 472 (4): 648-655.
6	Meng QQ, Liang XJ, Wang P, et al. Rosiglitazone enhances the proliferation of neural progenitor cells and inhibits inflammation response after spinal cord injury[J]. Neurosci Lett, 2011, 503 (3): 191-195.
7	Wnuk A, Kajta M. Steroid and xenobiotic receptor signalling in apoptosis and autophagy of the nervous system[J]. Int J Mol Sci, 2017, 18 (11): pii: E2394.
8	Wang CW, Klionsky DJ. The molecular mechanism of autophagy[J]. Mol Med, 2003, 9 (3-4): 65-76.
9	张向颖，魏琳琳，时红波，等.糖原合成酶激酶3β介导细胞自噬在急性肝衰竭中的作用[J/CD].中华危重症医学杂志（电子版），2017，10(6):361-366.
10	赵雯洁，王琛，孙波，等.硫化氢后处理对2型糖尿病大鼠心肌缺血再灌注损伤的保护作用及其与自噬潮的相关性研究[J/CD].中华危重症医学杂志（电子版），2016，9(2):81-86.
11	Tang P, Hou H, Zhang L, et al. Autophagy reduces neuronal damage and promotes locomotor recovery via inhibition of apoptosis after spinal cord injury in rats[J]. Mol Neurobiol, 2014, 49 (1): 276-287.
12	Zhang Q, Huang C, Meng B, et al. Changes in autophagy proteins in a rat model of spinal cord injury[J]. Chin J Traumatol, 2014, 17 (4): 193-197.
13	Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing[J]. EMBO J, 2000, 19 (21): 5720-5728.
14	Senna MK, Machaly SA. Does maintained spinal manipulation therapy for chronic nonspecific low back pain result in better long-term outcome?[J]. Spine (Phila Pa 1976), 2011, 36 (18): 1427-1437.
15	Chen HC, Fong TH, Lee AW, et al. Autophagy is activated in injured neurons and inhibited by methylprednisolone after experimental spinal cord injury[J]. Spine (Phila Pa 1976), 2012, 37 (6): 470-475.
16	Uchiyama Y, Shibata M, Koike M, et al. Autophagyphysiology and pathophysiology[J]. Histochem Cell Biol, 2008, 129 (4): 407-420.
17	Puyal J, Vaslin A, Mottier V, et al. Postischemic treatment of neonatal cerebral ischemia should target autophagy[J]. Ann Neurol, 2009, 66 (3): 378-389.
18	Meng QQ, Lei W, Chen H, et al. Combined rosiglitazone and forskolin have neuroprotective effects in SD rats after spinal cord injury[J]. PPAR Res, 2018: 3897478.
19	Li H, Zhang Q, Yang X, et al. PPAR-γ agonist rosiglitazone reduces autophagy and promotes functional recovery in experimental traumaticspinal cord injury[J]. Neurosci Lett, 2017 (650): 89-96.
20	Zhang Q, Hu W, Meng B, et al. PPARγ agonist rosiglitazone is neuroprotective after traumatic spinal cord injury via anti-inflammatory in adult rats[J]. Neurol Res, 2010, 32 (8): 852-859.
21	Shao ZQ, Liu ZJ. Neuroinflammation and neuronal autophagic death were suppressed via Rosiglitazone treatment: New evidence on neuroprotection in a rat model of global cerebral ischemia[J]. J Neurol Sci, 2015, 349 (1-2): 65-71.
22	Qin H, Tan W, Zhang Z, et al. 15d-prostaglandin J2 protects cortical neurons against oxygen-glucose deprivation / reoxygenation injury: involvement of inhibiting autophagy through upregulation of Bcl-2[J]. Cell Mol Neurobiol, 2015, 35 (3): 303-312.

[1]	Kang Li, Liang Ji, Wei Zhao, Lemin Lin. Dual role of autophagy in biological progression of breast cancer [J]. Chinese Journal of Breast Disease(Electronic Edition), 2023, 17(04): 195-202.
[2]	Hongxin Shi, Zhifang Tang, Minzheng Guo, Luqiao Pu, Baochuang Qi, Junxiao Ren, Chuan Li. Exploration of methodology and role of sodium iodoacetate in modeling of rat osteoarthritis [J]. Chinese Journal of Joint Surgery(Electronic Edition), 2023, 17(04): 534-539.
[3]	Yingying Kong, Lutao Xie, Xiaochi Lu, Jiefeng Xu, Guangju Zhou, Mao Zhang. Protective effect and mechanism of sodium butyrate on cardio-brain injury after cardiac arrest resuscitation in pigs [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(05): 355-362.
[4]	Ling Chen, Nan Li, Jianle Yang. Mechanism of microRNA-377-3p regulating autophagy to ameliorate lipopolysaccharide / D-galactosamine-induced acute liver failure [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(02): 89-97.
[5]	Xiaoyan Zhang, Dongqiong Xiao, Hu Gao, Lin Chen, Fajuan Tang, Xihong Li. The protective effect and mechanism of overexpression of transcription factor 12 on the cerebral cortex of rats with sepsis-associated encephalopathy [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 540-549.
[6]	Xiya Jin, Xiaosong Huang, Cheng Tan, Qin Jiang, Fang Hou, Yaoyue Li, Bing Xu, Honghui Jia, Wenying Liu. Antenatal treatment of tacrolimus on pulmonary vascular remodeling in rat with experimental pathological model of congenital diaphragmatic hernia [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(04): 428-436.
[7]	Zihui Zhou, Gongchi Li, Binghui Li, Zhi Wang, Huizhen Liu, Hui Wang, Lijun Zou. Advances of autophagy in wound healing [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2023, 18(06): 542-546.
[8]	Qiang Wei, Mingxiang Zhang, Qiangpu Chen, Baofang Sun. Effect of modified xiaochengqi decoction on the gastrointestinal motility of rats with obstructive jaundice [J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(04): 267-270.
[9]	Wentao Zhong, Yang Zhao, Xiaofei Shen, Junfeng Du. The role of autophagy in sepsis and progress in targeted therapy [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(02): 221-225.
[10]	Yuzhou Long, Hua Liu, Yunqian Zhang, Xingtong Li, Yunhu Fan, Zhengliang Shang, Zhenyu Song, Lihua Luo. Study on edaravone pretreatment prolonging thrombolytic time window by acute ischemic stroke and mechanism of ROS/TXNIP/NLRP3 pathway in rat [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2023, 13(02): 65-74.
[11]	Xiaohong Wang, Jing Qian, Wenjun Weng, Guoxiong Zhou, Shunxing Zhu, Xiaoming Qi, Chun Liu, Ping Wang, Wei Shen, Ruizhi Cheng, Jinghao Qin. Effects of regulation of nuclear factor-κB signal by mercaptopyruvate sulfurtransferase mediated autophagy on rats with severe acute pancreatitis and its mechanism [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 422-426.
[12]	Ruye Guo, Liming Meng, Nan Chen, Yuying Song, Haiyan Yin, Yan Guo. Research status on the neuroprotective efficacy and mechanism of Apelin/APJ system in Parkinson disease model [J]. Chinese Journal of Diagnostics(Electronic Edition), 2023, 11(04): 276-282.
[13]	Minchang Li, Changlin Ma. Research progress of autophagy regulating cell ferroptosis and the effects of ferroptosis in tumors [J]. Chinese Journal of Diagnostics(Electronic Edition), 2023, 11(02): 140-144.
[14]	Zhengda Li, Yanbin Zhang, Maoxia Liu, Xinjing Yang. Protective effect of esmolol on sepsis-induced intestinal injury and its mechanism [J]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2023, 09(02): 90-95.
[15]	Tian Qiu, Miaojuan Yang, Bo Hu, Yi Guo, Yitao He. Research progress on the mechanism of mild hypothermia therapy for cerebral infarction [J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2023, 17(05): 518-521.

Please choose a citation manager

Content to export