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The effect of the “segment” of spinal cord injury on the activity of the nucleotide‐binding domain‐like receptor protein 3 inflammasome and response to hormonal therapy
CELL BIOCHEMISTRY AND FUNCTION ( IF 3.6 ) Pub Date : 2020-09-07 , DOI: 10.1002/cbf.3574
Jamal Majidpoor 1, 2 , Keywan Mortezaee 3, 4 , Zahra Khezri 4 , Fardin Fathi 4 , Alireza Zali 5 , Homayoon Bana Derakhshan 6 , Mehdi Ghasemzadeh Bariki 7 , Mohammad Taghi Joghataie 1, 2, 8 , Reza Shirazi 1, 2 , Fatemeh Moradi 1, 2
Affiliation  

Spinal cord injury (SCI) is a common devastating condition that causes neuronal loss and dysfunction. Neuroinflammation takes cardinal roles in the pathogenesis of SCI, and nucleotide‐binding domain‐like receptor protein 3 (NLRP3) inflammasome is a mediator of inflammatory reactions occurring in SCI patients. The present study was designed to survey possible relation between thoracic segments whereby injury occurs with the activity of NLRP3 inflammasome complex, and to find the influence of hormonal therapy on the outcomes. Adult male Wistar rats underwent contusion SCI model at three different thoracic segments T1, T6 and T12, then receiving subcutaneous injection of either 10 mg/kg melatonin or 25 μg/kg 17‐β estradiol (E2) every 12 hours until 72 hours post‐SCI. Inflammasome activity was assessed before and at the end of hormonal therapy. SCI rats showed decreased locomotor activity and myelination, and increased activity of the NLRP3, apoptosis‐associated speck‐like protein (ASC) and caspase‐1 at gene and protein levels. Release of interleukins (ILs) 18 and 1β was also augmented after SCI (P < 0.0.5). Hormonal therapy was most effective for targeting mRNA activity at T6 segment. Treatment with either melatonin or E2 caused a decrease in the protein activity of NLRP3 inflammasome at all segments (P < 0.0.5), except for T6 that NLRP3 protein had no response to melatonin. IL‐1β showed decreased activity in response to hormonal therapy at all segments, whilst IL‐18 protein had no change at T1 segment. It is understood that although no alteration in the activity of NLRP3 was found for SCI at different segments, the response to hormonal therapy was influenced by segment.

中文翻译:

脊髓损伤“节段”对核苷酸结合域样受体蛋白3炎性小体活性和激素治疗反应的影响

脊髓损伤(SCI)是导致神经元丢失和功能障碍的常见破坏性疾病。神经炎症在SCI的发病机理中起主要作用,而核苷酸结合域样受体蛋白3(NLRP3)炎性小体是SCI患者发生炎症反应的介质。本研究旨在调查胸段之间可能发生的损伤与NLRP3炎性小体复合物的活性之间的关系,并探讨激素治疗对预后的影响。成年雄性Wistar大鼠在三个不同的胸段T1,T6和T12进行挫伤SCI模型,然后每12小时皮下注射10 mg / kg褪黑激素或25μg/ kg17-β雌二醇(E2),直到术后72小时SCI。在激素治疗之前和结束时评估炎症小体活性。SCI大鼠在基因和蛋白质水平上显示出自发活动和髓鞘减少,以及NLRP3,凋亡相关斑点样蛋白(ASC)和caspase-1的活性增加。SCI后白细胞介素(ILs)18和1β的释放也增加了(P <0.0.5)。激素疗法最有效地靶向T6区段的mRNA活性。褪黑激素或E2的治疗导致NLRP3炎性小体在所有区段的蛋白活性均降低(P <0.0.5),但T6除外,NLRP3蛋白对褪黑素无反应。IL-1β在所有节段均显示出对激素治疗的活性降低,而IL-18蛋白在T1节段无变化。可以理解,尽管在不同的节段中未发现SCI的NLRP3活性发生变化,但对激素治疗的反应受该节段的影响。
更新日期:2020-09-07
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