Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario Via C. Valeria, Gazzi, 98100, Messina, Italy.
Intensive Care Med. 2010 Jul;36(7):1235-47. doi: 10.1007/s00134-010-1798-4. Epub 2010 Mar 27.
Splanchnic artery occlusion (SAO) shock is a severe form of circulatory shock produced by ischemia and reperfusion of the splanchnic organs. The occlusion and reperfusion of the splanchnic arteries causes activation and adhesion of polymorphonuclear neutrophils (PMNs), release of proinflammatory substances and the formation of both species of oxygen and nitrogen derivatives free radicals. Olprinone is a specific phosphodiesterase-III inhibitor that has many properties; one of which is anti-inflammatory actions at therapeutic concentrations clinically used for heart failure. In this study, we wanted to evaluate the pharmacological action of olprinone (a PDEIII inhibitor) on SAO shock in mice.
SAO shock was induced by clamping both the superior mesenteric artery and the celiac trunk, resulting in a total occlusion of these arteries for 30 min. After this period of occlusion, the clamps were removed. Olprinone was given at a dose of 0.2 mg/kg i.p. 15 min before reperfusion.
Our results indicated that olprinone up-regulated cAMP in injured ileum tissue, and decreased the ileum tissue damage after 1 h of reperfusion in SAO shock mice. Moreover, olprinone decreased NF-kappaB expression; the nitration of tyrosine residues; the phosphorylation of p38 MAPK and JNK; cytokine production (TNF-alpha and IL-1beta); ICAM-1 and P-selectin expression and apoptosis in the injured ileum.
These results could imply a future use of olprinone in the therapy of ischemia and reperfusion shock.
内脏动脉闭塞（SAO）性休克是一种严重的循环休克形式，由内脏器官的缺血再灌注引起。内脏动脉的闭塞和再灌注导致多形核白细胞（PMN）的激活和黏附、促炎物质的释放以及氧和氮自由基两种物质的形成。奥普力农是一种特异性磷酸二酯酶-III 抑制剂，具有多种特性；其中之一是在临床心力衰竭治疗浓度下具有抗炎作用。在这项研究中，我们想评估奥普力农（一种 PDEIII 抑制剂）对 SAO 休克小鼠的药理作用。
通过夹闭肠系膜上动脉和腹腔干来诱导 SAO 性休克，导致这些动脉完全闭塞 30 分钟。闭塞期结束后，松开夹闭。奥普力农在再灌注前 15 分钟以 0.2mg/kg i.p. 的剂量给药。
我们的结果表明，奥普力农在上皮损伤的回肠组织中上调 cAMP，并降低了 SAO 休克小鼠再灌注 1 小时后的回肠组织损伤。此外，奥普力农降低了 NF-κB 的表达；酪氨酸残基的硝化；p38MAPK 和 JNK 的磷酸化；细胞因子（TNF-α和 IL-1β）的产生；ICAM-1 和 P-选择素的表达和损伤回肠中的细胞凋亡。
这些结果可能意味着奥普力农在未来可用于治疗缺血再灌注性休克。
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