Effects of RIPK1 inhibitor necrostatin-1s on cardiovascular responses and inflammatory damage in a bilateral hind limb I/R injury model in rats

Abstract

Objectives : This study investigated the effects of the receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitor necrostatin-1s (Nec-1s) on cardiovascular responses and inflammatory damage in a bilateral hind limb ischemia/reperfusion (I/R) injury model in rats. Methods : The I/R injury model consisted of 3 h of ischemia followed by 24 h of reperfusion. Nec-1s was injected intraperitoneally into the rats 1 h before reperfusion. Results : Nec-1s prevented the hypotensive and tachycardic responses to I/R. The I/R-induced increases in the expression or activity of RIPK1, RIPK3, mixed lineage kinase domain-like pseudokinase, high-mobility group box 1, inhibitor of κB kinase α/β/γ, inhibitor of κBα, nuclear factor-kB p65, inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β in cardiac, renal, pulmonary, hepatic, and cerebral tissues, as well as in the serum nitrite and prostaglandin I 2 levels of the rats, were prevented by Nec-1s. Nec-1s attenuated the elevation in scores for I/R-induced histopathological changes only in the heart. Conclusion : These findings revealed that Nec-1s prevents the deterioration of cardiovascular responses and inflammatory tissue damage in a hind limb I/R model in rats.