Researchon Mechanisms of Dexmedetomidine Alleviating Early Brain Injury in Rats with Subarachnoid Hemorrhage by Down-regulating the Expression of NLRP3 Inflammatory Bodies
PENG Chengxu, XIANG Hong, JIN Tao, et al
Minda Hospital Affiliated to Hubei University for Nationalities, Hubei Enshi 445000, China
Abstract：Objective: To investigate the mechanism of dexmedetomidine in reducing early brain injury in rats with subarachnoid hemorrhage by down-regulating the expression of NLRP3 inflammatory body. Methods: 100 healthy SD rats were randomly divided into healthy control group, model group and dexmedetomidine group (low dose group, middle dose group and high dose group), 20 rats in each group. Rats in model group and dexmedetomidine group were used to construct subarachnoid hemorrhage model by internal carotid artery puncture. After the model was established, surviving rats were identified as successful subarachnoid hemorrhage model by Garcia method. After the completion of the model, rats in the model group were injected with normal saline and rats in the dexmedetomidine group were injected with high, medium and low doses of dexmedetomidine respectively. The rats were sacrificed after 7 days of continuous administration. The amount of subarachnoid hemorrhage and water content in the brain were measured and compared. The levels of serum inflammatory factors were detected by ELISA, and the levels of NLRP3 were detected by immunohistochemical method. Pearson correlation test was used to analyze the correlation between inflammatory factors such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and NLRP3 levels. Results: Compared with healthy control group, the amount of subarachnoid hemorrhage and water content in brain of model group and dexmedetomidine group increased significantly, and the amount of subarachnoid hemorrhage and water content in brain of dexmedetomidine group decreased. The amount of hemorrhage and water content of dexmedetomidine group decreased with the increase of dosage. There was significant difference between the two groups (P<0.05). Compared with the healthy control group, the levels of IL-1beta, TNF-alpha, IL-6 and NLRP3 in the model group and dexmedetomidine group were significantly higher, and the levels of inflammatory factors in dexmedetomidine group were lower than those in the model group. The levels of inflammatory factors in dexmedetomidine group decreased gradually with the increase of dosage, and there were significant differences among the groups (P<0.05). Pearson correlation test showed that NLRP3 was positively correlated with IL-1beta, TNF-alpha and IL-6 (P<0.05). Conclusion: dexmedetomidine can reduce the degree of early brain injury, inflammatory response and NLRP3 level in rats with subarachnoid hemorrhage, and the mechanism may be related to down-regulation of the expression of NLRP3 inflammatory bodies.
彭承旭, 向红, 金涛, 田香. 右美托咪定通过下调NLRP3炎性小体的表达减轻蛛网膜下腔出血大鼠早期脑损伤的机制研究[J]. 河北医学, 2020, 26(2): 202-204.
PENG Chengxu, XIANG Hong, JIN Tao, et al. Researchon Mechanisms of Dexmedetomidine Alleviating Early Brain Injury in Rats with Subarachnoid Hemorrhage by Down-regulating the Expression of NLRP3 Inflammatory Bodies. HeBei Med, 2020, 26(2): 202-204.
[1] 杨毅,官俏兵,郭丽,等.樟芝多糖通过降低NLRP3-Caspase1炎性小体表达改善帕金森小鼠神经行为学的机制研究[J].中国临床药理学与治疗学,2018,23(4):406~412. [2] 崔东娟,刘涛,赵艳红.香叶木素降低NLRP3炎性小体活性缓解CCl_4诱导的肝损伤大鼠肝纤维化[J].中国免疫学杂志,2019,29(5):555~559. [3] 邓丽丽,王佳文,袁丁,等.竹节参总皂苷通过NLRP1和NLRP3炎症小体途径减轻衰老大鼠神经细胞凋亡的作用研究[J].中草药,2017,48(23):4941~4951. [4] 李建华,孙娟,张艳,等.线栓长度对颈内动脉穿刺法建立大鼠蛛网膜下腔出血模型的影响[J].青海医学院学报,2014,35(3):191~194. [5] Hu J, Gu X Y, Meng Y, et al. Effect of dexmedetomidine postconditioning on myocardial ischemia-reperfusion injury and inflammatory response in diabetic rats.[J]. Journal of Southern Medical University, 2017, 37(11):1506~1511. [6] Okazaki T, Hifumi, Toru, Kawakita, Kenya, et al. Association between dexmedetomidine use and neurological outcomes in aneurysmal subarachnoid hemorrhage patients: A retrospective observational study[J]. Journal of Critical Care, 2017, 44(8):111~116. [7] Zhou K, Enkhjargal, Budbazar, Xie, Zhiyi, et al. Dihydrolipoic Acid Inhibits Lysosomal Rupture and NLRP3 Through Lysosome-Associated Membrane Protein-1/Calcium/Calmodulin-Dependent Protein Kinase II/TAK1 Pathways After Subarachnoid Hemorrhage in Rat[J]. Stroke, 2018, 49(1):175~183. [8] Yin D, Zhou Shuai, Xu Xin, et al. Dexmedetomidine attenuated early brain injury in rats with subarachnoid haemorrhage by suppressing the inflammatory response: The TLR4/NF-κB pathway and the NLRP3 inflammasome may be involved in the mechanism[J]. Brain Research, 2018, 18,2(8):278~286.
2020, Vol. 26 
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