Effects of the cannabinoid antagonist AM281 on systemic hemodynamics and mortality rate in streptozotocin-induced diabetic rats with endotoxic shock: comparison between non-diabetic and diabetic rats
Effects of the cannabinoid antagonist AM281 on systemic hemodynamics and mortality rate in streptozotocin-induced diabetic rats with endotoxic shock: comparison between non-diabetic and diabetic rats
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DOI：
10.1111/j.1399-6576.2007.01573.x
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发表时间：
2008-05-01
影响因子：
2.1
通讯作者：
Saito, S.
中科院分区：
文献类型：
--
作者：
Kadoi, Y.;Hinohara, H.;Saito, S.
目的：在前期发现内源性大麻素受体拮抗剂大麻素拮抗剂AM281能够恢复非糖尿病大鼠脓毒症期间的血流动力学和脑血流变化并提高死亡率的基础上，本研究旨在探讨AM281是否能够恢复链脲佐菌素诱导的糖尿病大鼠的血流动力学参数并改善脓毒症期间的死亡率。 方法：该研究设计包括三组实验，每组实验均在糖尿病和非糖尿病动物中进行：（1）测量全身血流动力学和颈动脉血流量的变化，（2）测量生化变量和（3）评估死亡率。在治疗前以及治疗后 1、2 和 3 小时评估全身血流动力学、颈动脉血流变化和生化变量。 结果：在非糖尿病和糖尿病大鼠中，给予脂多糖 (LPS) 均会导致血流动力学变量减少，糖尿病大鼠的血流动力学变量减少幅度大于非糖尿病大鼠。在糖尿病大鼠中，施用 AM281 只能部分阻止这些血流动力学变化，这些变化不足以将这些变量提高到控制值。在接受相同治疗的非糖尿病组和糖尿病组之间，6 小时和 12 小时的死亡率存在显着差异。 12小时时，只有非糖尿病AM281组大鼠仍存活（死亡率50%）。结论：AM281仅部分预防了糖尿病大鼠与LPS诱导的败血症相关的血流动力学、生化和颈动脉血流变化，而非糖尿病大鼠则更大程度地预防了这些变化。
Purpose: On the basis of previous findings that the anandamide antagonist AM281, an endogenous cannabinoid receptor antagonist, could restore the hemodynamic and cerebral blood flow changes and improve the mortality rate in non-diabetic rats during sepsis, this study was conducted to examine whether AM281 could restore the hemodynamic variables and improve the mortality rate in streptozotocin-induced diabetic rats during sepsis.Methods: The study was designed to include three sets of experiments, each set of experiment being conducted in both diabetic and non-diabetic animals: (1) measurement of changes in systemic hemodynamics and carotid artery blood flow, (2) measurement of biochemical variables and (3) assessment of mortality rate. Systemic hemodynamics, carotid artery blood flow changes and biochemical variables were assessed at pre-treatment and 1, 2 and 3 h after the treatment was performed.Results: In both non-diabetic and diabetic rats, administration of lipopolysaccharide (LPS) induced a reduction in hemodynamic variables, these reductions being greater in diabetic than in non-diabetic rats. In diabetic rats, administration of AM281 could only partially prevent these hemodynamic changes, these changes being insufficient to elevate these variables to control values. Significant differences were observed in mortality rates at 6 and 12 h between non-diabetic and diabetic groups with the same treatment. At 12 h, only non-diabetic AM281 group rats were still alive (mortality rate 50%).Conclusion: Administration of AM281 only partially prevented the hemodynamic, biochemical and carotid artery blood flow changes associated with LPS-induced septicemia in diabetic rats, as compared with non-diabetic rats in whom these changes were prevented to a greater extent.