Benefits of anti‑inflammatory therapy in the treatment of ischemia/reperfusion injury in the renal microvascular endothelium of rats with return of spontaneous circulation.

Abstract

The aim of the present study was to investigate whether prostaglandin E1 (PGE1), target temperature management (TTM) and a combined intervention involving the two would be beneficial as anti‑inflammatory therapies for ischemia/reperfusion (I/R) injury to the renal microvascular endothelium of rats with return of spontaneous circulation (ROSC). In each group of rats with different interventions, following successful cardiopulmonary resuscitation, the levels of thrombomodulin (TM), interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α) in the plasma were evaluated. The expression of vascular endothelial (VE)‑cadherin and vascular cell adhesion molecule‑1 (VCAM‑1) mRNA was analyzed in the kidney. Hematoxylin and eosin staining and VE‑cadherin/vascular endothelial growth factor receptor double fluorescent immunohistochemistry staining were also performed. PGE1 improved tubular cell swelling and inflammatory cell infiltration. PGE1 also alleviated VE‑cadherin protein loss in renal microvascular endothelium cells (RMECs), lowered the tubular injury score, decreased VE‑cadherin and VCAM‑1 mRNA expression, and markedly inhibited the release of TM (at 3 time points) and TNF‑α (4 and 8h; P<0.05). In addition to improving the renal tubular injury score and altering the concentration of TNF‑α at 8h, the effect of TTM was the same as PGE1 for the other indicators (P>0.05). The PGE1/TTM combined intervention significantly reduced IL‑6 concentration at 8h (P<0.05). The correlation analysis demonstrated that the peak TM and TNF‑α levels (P<0.001, r=0.809), and IL‑6 levels (P<0.001, r=0.792) were positively associated. PGE1 and TTM had a protective effect against I/R injury to the RMEC, while the PGE1/TTM combined intervention exhibited an increased synergistic effect as an anti‑inflammatory treatment when compared with either of the single interventions.