Irisin Protects Against Motor Dysfunction of Rats with Spinal Cord Injury via Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase-Nuclear Factor Kappa-B Pathway.
Irisin Protects Against Motor Dysfunction of Rats with Spinal Cord Injury via Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase-Nuclear Factor Kappa-B Pathway.
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DOI：
10.3389/fphar.2020.582484
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发表时间：
2020
影响因子：
5.6
通讯作者：
Ni W
中科院分区：
文献类型：
--
作者：
Jiang X;Shen Z;Chen J;Wang C;Gao Z;Yu S;Yu X;Chen L;Xu L;Chen Z;Ni W
本研究旨在观察骨骼肌源性肌细胞因子Irisin对大鼠脊髓损伤（SCI）的影响，并探讨其可能的作用机制。雄性SD大鼠建立脊髓损伤模型。采用行为学检查（BBB评分法）和斜面实验，组织形态学检查（HE染色、Nissl染色、透射电镜观察），观察鸢尾素对SCI大鼠的影响。采用PCR、Western blot和ELISA等生化分析方法，进一步从分子水平评价脊髓损伤大鼠的变化。此外，建立了脂多糖（LPS）诱导的PC 12细胞损伤模型，以验证鸢尾素对体外神经细胞的作用机制。结果表明，脊髓损伤后BBB评分和倾斜角度明显下降，而长期使用鸢尾素治疗可改善脊髓损伤引起的运动功能障碍。HE和Nissl染色结果显示，SCI手术后脊髓组织学损伤明显，Irisin可逆转SCI后脊髓组织学损伤。鸢尾素还能减轻脊髓损伤后神经细胞的形态学异常。进一步的生物化学分析显示，在大鼠中，鸢尾素抑制SCI诱导的白细胞介素-1 β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子α（TNF-α）、诱导型一氧化氮合酶（iNOS）和环氧合酶-2（考克斯-2）]以及核因子κ-B（NF-κB）p65的过表达，并且鸢尾素的正功能可以被化合物C处理逆转。在我们的体外研究中，Irisin可抑制LPS诱导的PC 12细胞存活率和突起长度的下降，并抑制LPS诱导的NF-κ Bp 65、IL-1β、IL-6、TNF-α、iNOS和考克斯-2的过表达。这些变化可以通过活化蛋白激酶（AMPK）siRNA预处理来逆转。综上所述，鸢尾素对大鼠脊髓损伤具有保护作用，其保护作用与调节5 '-磷酸腺苷活化蛋白激酶（AMPK）- NF-κB信号通路有关。
The aim of the present research was to investigate the effects of irisin, a skeletal muscle-derived myokine, on spinal cord injury (SCI) in rats and explore the possible mechanisms. SCI model was constructed in male SD rats. The effects of irisin on SCI rats were assessed via behavior tests including Basso, Beattie, and Bresnahan (BBB) scoring method and inclined plane test, followed by histomorphology tests including HE staining, Nissl staining, and transmission electron microscope examination. Biochemical analyses including PCR, Western blots and ELISA were employed to further evaluate the changes at molecular level of SCI rats. In addition, lipopolysaccharide (LPS)-induced cell damage model was established in PC12 cells to verify the mechanism of irisin’s effect on nerve cells in vitro. Results showed that the BBB score and the angle of incline significantly decreased after SCI surgery, however, chronic irisin treatment improved SCI-induced motor dysfunction. HE and Nissl staining assays showed that SCI surgery induced histological injury of spinal cord, which could be reversed by irisin treatment. Morphological abnormality of nerve cells caused by SCI also could be alleviated by irisin. Further biochemical analyses showed that irisin inhibited SCI-induced overexpression of Interleukin-1β (IL-1β), Interleukin- 6 (IL-6), tumor necrosis factor alpha (TNF-α), inducible nitricoxidesynthase (iNOS) and Cyclooxygenase-2 (COX-2)], as well as nuclear factor kappa-B (NF-κB)p65 in rats, and the positive function of irisin could be reversed by Compound C treatment. In our in vitro study, LPS-induced declines of cell viability and neurite length of PC12 cell were inhibited by irisin treatment, and irisin inhibited LPS-induced overexpression of NF-κBp65, IL-1β, IL-6, TNF-α, iNOS and COX-2. These changes could be reversed by activated protein kinase (AMPK) siRNA pre-treatment. Taken together, irisin could protect the rats from SCI, and its protection is associated with the regulation of adenosine 5'-monophosphate-activated protein kinase (AMPK)- NF-κB signaling pathway.
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