Ulinastatin improves renal microcirculation by protecting expression of VE-cadherin and inhibiting autophagy in a septic rat model

Abstract Background: Increased permeability of the renal capillary is a common consequence of sepsis-associated acute kidney injury. Vascular endothelial (VE)-cadherin is a strictly endothelial-specific adhesion molecule that can control the permeability of the blood vessel wall, and autophagy plays an important role in maintaining cell stability. Ulinastatin, a urinary trypsin inhibitor, attenuates the systemic inflammatory response and visceral vasopermeability. However, it is uncertain whether ulinastatin can improve renal microcirculation by acting on the adhesion junction. Methods: We obserned the effect of Ulinastatin in the septic rat model by using contrast-enhanced ultrasonography (CEUS) to evaluate perfusion of the renal cortex and medulla. Male adult Sprague-Dawley rats were subjected to cecal ligation and puncture and divided into the sham, sepsis, and ulinastatin groups. Ulinastatin (50 000 U/kg) was injected into the tail vein 1 hour after the operation. At 24 hours postoperatively, CEUS was performed to evaluate the renal microcirculation blood flow and microcirculation perfusion. Histological staining was used to evaluate kidney injury scores. Western blotting was used to assess the expression of VE-cadherin and LC3II, peripheral serum cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α levels), renal function (creatinine, urea nitrogen, and S-thrombomodulin level), and the urine neutrophil gelatinase-associated lipocalin level. Results: Compared with sham group, ulinastatin reduced the inflammatory response, maintained the expression of VE-cadherin, inhibited autophagy, and meliorated cortical and medullary perfusion.Conclusions: Ulinastatin effectively protects the adhesion junction and helps to ameliorate the perfusion of kidney capillaries during sepsis by inhibiting autophagy and the expression of inflammatory factors.