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| 右美托咪定在脂多糖诱导脓毒症小鼠神经炎症损伤中的作用 |
| Effect of dexmedetomidine on neuroinflammation induced by lipopolysaccharide in septic mice |
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| DOI：10.12089/jca.2021.08.015 |
| 中文关键词: 右美托咪定 脂多糖 神经炎症 炎性因子 微小RNA |
| 英文关键词: Dexmedetomidine Neuroinflammation Lipopolysaccharide Inflammatory factor MicroRNA |
| 基金项目:“新晨杯”优秀青年麻醉医师科研项目 |
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| 中文摘要: |
目的 通过观察右美托咪定应用于脂多糖（LPS）诱导的脓毒症小鼠炎性因子浓度和炎性微小RNA（miRNAs）表达量的变化，探讨右美托咪定在神经炎症损伤中的作用及分子机制。
方法 清洁级ICR雄性小鼠160只，8～12周龄，体重20～25 g。采用随机数字表法分为四组：生理盐水组（C组）、右美托咪定组（D组）、LPS组（L组）和LPS+右美托咪定组（LD组），每组40只。C组每隔2 h腹腔注射生理盐水0.5 ml，共3次；D组每隔2 h腹腔注射右美托咪定 40 μg/kg加生理盐水的混合液0.5 ml，共3次；L组腹腔注射LPS 12 mg/kg建立脓毒症模型，建立模型后30 min，每隔2 h腹腔注射生理盐水0.5 ml，共3次；LD组腹腔注射LPS 12mg/kg建立脓毒症模型，建立模型后30 min，每隔2 h腹腔注射右美托咪定 40 μg/kg加生理盐水的混合液0.5 ml，共3次。于建立脓毒症模型后8、24 h取小鼠海马组织，采用ELISA法检测海马组织IL-18和IL-1β浓度，RT-PCR法检测海马组织和血液miR-155、miR-146、miR-21、miR-181、miR-223表达量。于建立脓毒症模型后24 h，采用TUNEL法检测海马组织神经元凋亡细胞百分比。
结果 与C组比较，建立模型后8、24 h L组和LD组海马组织IL-1β和IL-18浓度明显升高（P<0.05），L组海马组织和血液miR-155、miR-21表达量明显升高（P<0.05），miR-146、miR-181、miR-223表达量明显降低（P<0.05），LD组血液miR-181、miR-223表达量明显升高（P＜0.05）；建立模型后24 h L组海马组织神经元凋亡细胞百分比明显升高（P＜0.05）。与L组比较，建立模型后8、24 h LD组海马组织IL-18、IL-1β浓度明显降低（P<0.05），海马组织和血液miR-155、miR-21表达量明显降低（P<0.05），miR-146、miR-181、miR-223表达量明显升高（P<0.05），建立模型后24 h LD组海马组织神经元凋亡细胞百分比明显降低（P＜0.05）。C组和D组各项指标差异均无统计学意义。
结论 右美托咪定通过调节炎性因子浓度和炎性miRNAs表达量，降低海马组织神经元凋亡细胞百分比，从而减轻脂多糖诱导的脓毒症小鼠神经炎症损伤。 |
| 英文摘要: |
Objective To investigate the neuroprotective molecular mechanism of dexmedetomidine by observing the changes of inflammatory factor concentration and inflammatory miRNAs expression by the use of dexmedetomidine in lipopolysaccharide (LPS)-induced sepsis mice.
Methods A tolal of 160 healthy ICR male mice were randomly divided into four groups, including normal saline group (group C), dexmedetomidine treatment group (group D), LPS-induced neuroinflammation group (group L), LPS + dexmedetomidine group (group LD), 40 mice in each group. 0.5 ml nomal saline was administered in group C every two hours for three times. Dexmedetomidine 40 μg/kg add nomal saline 0.5 ml was administered in group D every two hours for three times. Intraperitoneal injection of LPS 12 mg/kg used to establish septic mice model, 30 minutes after the establishment, 0.5 ml of nomal saline was administered in group L every two hours for three times. 0.5 ml dexmedetomidine 40 μg/kg add nomal saline was administered every two hours for three times after establishing septic mice model 30 minutes in group LD. The hippocampal tissue of mice were collected at 8 and 24 hours after the establishment of sepsis mice model. The concentration of IL-18 and IL-1β in hippocampal tissue were determined by enzyme-linked immune absotbent assay (ELISA). The expression of miR-155, miR-146, miR-21, miR-181 and miR-223 in hippocampal tissue and blood were detected by RT-PCR. Another 8 mice were fixed for in situ terminal staining (TUNEL staining) in each group to detect the percentage of apoptotic neurons in hippocampus 24 hours after the establishment of sepsis mice model.
Results Compared with group C,the content of IL-1β and IL-18 in hippocampus were significantly increased after 8 and 24 hours in group L and group LD (P < 0.05), the gene expressions of miR-155, miR-21 in hippocampus and blood in group L were significantly increased after 8 and 24 hours (P < 0.05), the gene expressions of miR-146, miR-181, miR-223 in hippocampus and blood in group L were significantly decreased after 8 and 24 hours (P < 0.05), the gene expressions of miR-181 and miR-223 in blood in group LD were significantly increased after 8 and 24 hours, the TUNEL staining indicated a significantly increased percentage of apoptotic cells in hippocampal neurons of group L after 24 hours (P < 0.05). Compared with group L, the concentrations of IL-1β and IL-18 in hippocampus were significantly decreased at 8 and 24 hours in group LD (P < 0.05). After 8 and 24 hours, the gene expressions of miR-155, miR-21 in hippocampus and blood in group LD were significantly lower than those of the group L (P < 0.05), and the gene expressions of miR-146, miR-181, miR-223 in hippocampus and blood in group LD were significantly increased (P < 0.05), the TUNEL staining indicated a significantly decreased percentage of apoptotic cells in hippocampal neurons of group LD after 24 hours (P < 0.05). There were no significant diffrence between group C and group D.
Conclusion Dexmedetomidine may decrease the percentage of apoptotic neurons in the hippocampus by regulating the concentration of inflammatory factors and the genes expression of inflammatory miRNAs, subsequently alleviate the neuroinflammatory damage induced by LPS in sepsis mice. |
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