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目的：观察右美托咪啶对脓毒症大鼠肾脏功能及Toll 受体4 表达的影响，探讨减轻脓毒症损害的潜在治疗方案。方法：选择雄性SD 大鼠作为研究对象，采取盲肠结扎穿孔方法建立脓毒症模型；取模型制备成功的大鼠按照数字随机法分为3 组，A 组为空白对照组，泵注1.0 mL/kg 生理盐水，B 组为对照组，术毕泵注1.0 mL/kg 生理盐水，维持10 min，持续泵注NS 1.0 mL/kg·h，C 组为实验组，术毕给予右美托咪定5 滋g/kg，维持10 min，持续泵注右美托咪定4.5 滋g/kg·h，3 组均持续泵注24 h，并于6 h、12 h、 24 h各组分别取8 只大鼠检测中性粒细胞明胶酶相关脂质运载蛋白（NGAL）表达水平进行比较，并观察比较3 组研究对象尿素氮（BUN）、肌酐清除率（Ccr)以及肾脏组织Toll 受体4水平及TLR4 mRNA水平。结果：C 组大鼠应用右美托咪定后，BUN于6 h、 12 h、24 h分别为（13.4± 1.2）mmol/L、（12.5± 1.3）mmol/L、（11.4± 1.1）mmol/L，均低于A 组、B组，均P<0.05；Ccr 于6 h、12 h、24 h 分别为（77.4± 9.9）mL/min、（75.4± 10.2）mL/min、（78.5± 11.3）mL/min，均明显低于A 组、B 组，P<0.05；C 组6 h、12 h、24 h NGAL 表达水平分别为（39.2± 9.9）pg/mL、（41.6± 9.8）pg/mL、（38.2± 9.9）pg/mL，均明显低于A组、B组，P<0.05；C 组泵注6 h、12 h、24 h Toll受体4 水平及TLR4 mRNA 水平均低于A 组、B 组，P<0.05。结论：右美托咪啶可降低脓毒症大鼠Toll 受体4表达，有助于减轻脓毒症炎性反应与减轻肾损害，具有重要临床价值。

英文摘要:

Objective:To observe the effect of dexmedetomidine on renal function and the expression of Toll receptor 4 of sepsis rat models, to investigate the potential therapeutic scheme to reduce damage induced by sepsis.Methods:SD rats were selected as the research objects, and they were divided into 3 groups according to random number table. All three groups were performed cecal ligation and puncture to establish the model of sepsis. The rats were injected 5 mg/kg LPS through tail vein indwelling needle; after establishing the model,A group was blank control group which was treated with 1.0 mL/kg normal saline infusion, and the rats of B group was treated with 1.0 mL/kg normal saline infusion with maintaining 10 min, then continuous NS 1.0 mL/kg·h, and the rats of C group received 5 ug/kg dexmedetomidine with maintaining 10 min, then continuous infusion of dextromethorphan with 4.5 ug/kg·h. All groups maintain continuous infusion for 24 h. The expression level of neutrophils enzyme related lipid carrier protein gelatin (NGAL) in 6 h, 12 h, 24 h was detected and the level of blood urea nitrogen (BUN) and creatinine clearance rate (Ccr) and Toll receptors 4 and TLR4mRNA was detected and compared among groups.Results:The BUN of group C after the application of dexmedetomidine on 6 h, 12 h, 24 h were (13.4 ± 1.2) mmol/L, (12.5 ± 1.3) mmol/L, (11.4 ± 1.1) mmol/L and were lower than those of group A, group B, P<0.05; the Ccr of group C on 6 h, 12 h and 24 h were (77.4 ± 9.9) mL/min, (75.4 ± 10.2) mL/min, (78.5 ± 11.3) mL/min and were significantly lower than those of group A, group B , P<0.05; the level of NGAL expression of group C on 6 h ,12 h, 24 h were (39.2 ± 9.9) pg/mL, (41.6 ± 9.8) pg/mL, (38.2 ± 9.9) pg/mL, obviously lower than that of group A and B, P<0.05. The level of TLR4 and TLR4 mRNA of group C on 6 h, 12 h, 24 h were lower than those of group A and B, P<0.05.Conclusion:Dexmedetomidine can reduce the expression of Toll receptor 4 in sepsis rats , and contribute to relieve the inflammatory response to sepsis and reduce renal damage, so it has important value.

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