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Chinese Journal of Neurotraumatic Surgery(Electronic Edition) ›› 2017, Vol. 03 ›› Issue (05): 277-283. doi: 10.3877/cma.j.issn.2095-9141.2017.05.006

Special Issue:

• Basic Research • Previous Articles     Next Articles

Effects of necroptosis induced by receptor interacting-protein 3 in traumatic brain injury model of C57/BL mice

Zeqi Yu1, Tailong Yi2, Yue Tu2, Xiaosa Yang2, Jipeng Jiang2, Xiaoyu Dong3, Sai Zhang2, Shixiang Cheng2,()   

  1. 1. First Department of Surgery, the Chengdu Hospital of Sichuan Armed Police Corps, Chengdu 610041, China
    2. Neurology and Neurosurgery Hospital, Affiliated Hospital of Logistics College of Chinese People’s Armed Police Force, Tianjin 300162, China
    3. Medical Unit of Three Department of Beijing Armed Police Corps, Beijing 100621, China
  • Received:2017-05-08 Online:2017-10-15 Published:2017-10-15
  • Contact: Shixiang Cheng
  • About author:
    Corresponding author: Cheng Shixiang, Email:

Abstract:

Objective

To investigate the effects of necroptosis induced by receptor interacting-protein 3 (RIP3) on traumatic brain injury (TBI) model of C57BL/6 mice and its mechanisms.

Methods

C57BL/6 mice were positioned beneath the controlled cortical impactor device (CCI) and subjected to impact injury at 1 mm depth of penetration, for a sustained depression of 120 msec and a velocity of 5 m/s. Ctrl group was not treated. Sham group was received craniotomy, without CCI injury. TBI group was received CCI injury and 4 μl DMSO injected. GSK’872 group was received CCI injury and 4 μl GSK’872 injected. Then, the degree of injury was detected by modified neurological severity scores (mNSS), the degree of brain edema was measured with drying wet method, the injure degree of cortex and hippocampus was assessed by HE staining, the recovery after CCI was measured by awakening time and the expressions of RIP3/RIP1/MLKL, Akt/p-Akt/mTOR/p-mTOR, Caspase-8/XIAP, Caspase-1/NLRP3 were detected by Western blot assay.

Results

Compared with TBI group, GSK’872 could significantly decrease the score of mNSS [1 d: (11.95±1.50) vs (13.05±1.82), t=2.084, P<0.05; 3 d: (8.95±1.39) vs (11.00±2.10), t=3.634, P<0.01: 5 d: (6.75±1.33) vs (8.90±1.52), t=4.759, P<0.01; 7 d: (4.00±1.08) vs (7.15±1.09), t=9.200, P<0.01], decrease the degree of brain edema [(77.91±0.84)% vs (80.34±0.94)%, t=8.692, P<0.01], reduce the degree of injury in cortex and hippocampus, and promote the awaking of mice after CCI[(4.08±0.63) h vs (5.11±0.74) h, t=4.717, P<0.01]. Furthermore, Western blotting assay reveled that GSK’872 could significantly decrease the levels of RIP3[(0.70±0.03) vs(1.04±0.04), t=13.051, P<0.01], RIP1[(0.93±0.02) vs (1.16±0.03), t=11.203, P<0.01], MLKL[(0.75±0.04) vs (1.03±0.03), t=9.873, P<0.01], Akt[(0.55±0.04) vs (0.77±0.05), t=6.278, P<0.01], p-Akt[(0.80±0.04) vs (0.99±0.04), t=6.217, P<0.01], mTOR[(0.48±0.05) vs (0.90±0.05), t=10.608, P<0.05], p-mTOR[(0.59±0.06) vs (1.00±0.05), t=9.144, P<0.01], Caspase-1[(0.80±0.04) vs (0.98±0.05), t=5.226, P<0.01], NLRP3[(0.51±0.03) vs (0.89±0.03), t=15.590, P<0.01], XIAP[(0.50±0.03) vs (0.83±0.03), t=13.340, P<0.01], but increase the level of Caspase-8 compared with TBI group [(0.83±0.03) vs (0.71±0.03), t=5.044, P<0.01].

Conclusion

Necroptosis induced by RIP3 may play an important role in TBI, however, GSK’872 could reduce the degree of injury after TBI, which reveals that RIP3 may be a new target for clinical treatment of TBI in the future.

Key words: Receptor-interacting protein3, Traumatic brain injury, Necroptosis

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