Objective: To explore the effect of dexmedetomidine (DEX) on high-mobility group box 1 protein (HMGB1) in the serum and spleen in rats with sepsis and the underlying mechanisms.
Methods: A total of 100 male Wistar rats were randomly divided into five groups: a control group, a sepsis group, a DEX group, an α-bungarotoxin- tetramethylrhodamine (α-BGT) plus DEX group and an α-BGT group (n=20 in each group). In the control group, same volume of normal saline (NS) was administrated, while lipopolysaccharide (LPS) was injected to the vein to develop a classic sepsis model. At the 48th h after LPS injection, the rats were sacrificed, and the blood and spleen were collected. The content of tumor necrosis factor-α (TNF-α) and HMGB1 in blood serum were detected by enzyme-linked immuno sorbent assay (ELISA), and the HMGB1 in the spleen was examined by Western blot.
Results: Among the 5 groups, there were statistical significance in the mortality, the serum level of TNF-α and HMGB1, and the content of secreting type of HMGB1 in spleen (all P<0.05), and the serum level of HMGB1 was positively correlated with the content of secreting type of HMGB1 (r=0.863, P<0.05).
Conclusion: DEX exert late anti-inflammatory effects in the serum and spleen in rats with sepsis, which is related to the activation of the cholinergic anti-inflammatory pathway.
目的：探讨右美托咪定(dexmedetomidine，DEX)对脓毒症大鼠血液和脾组织中高迁移率族蛋白B1(high-mobility group box 1 protein，HMGB1)的作用及其可能的机制。方法：将100只雄性Wistar大鼠随机分为对照组、模型组、DEX组、α-银环蛇毒素(α-bungarotoxin-tetramethylrhodamine，α-BGT)+DEX组和α-BGT组，每组20只。对照组静脉注射等量的生理盐水，其余各组均通过静注内毒素(lipopolysaccharide，LPS)构建脓毒症模型，并给予不同的处理，48 h后处死大鼠，留取血液及脾组织标本。应用ELISA分别检测血液中TNF-α和晚期炎症介质HMGB1的水平，Western印迹检测脾组织中HMGB1的含量。结果：5组大鼠间病死率、血清TNF-α水平、HMGB1的血清水平和脾组织含量差异均有统计学意义(均P<0.05)，且HMGB1的血清水平和脾组织含量存在显著相关性(r=0.863，P<0.05)。结论：DEX可明显降低脓毒症大鼠血液及脾组织中晚期炎症介质HMGB1的含量，这种作用可能是通过激活胆碱能抗炎通路而实现的。.