The Protective Effects of Sivelestat Sodium on Hepatic and Renal Organs in Rats Undergoing Deep Hypothermic Circula-tory Arrest

TENG Yuan; WANG Tianlong; BIAN Luyu; WANG Jian; YAN Shujie; JI Bingyang; HU Qiang

doi:10.13498/j.cnki.chin.j.ecls.2025.05.12

Abstract：Objective To investigate the hepatorenal protective effects of sivelestat sodium in rats undergoing deep hy-pothermic circulatory arrest(DHCA).Methods Eighteen rats were randomly divided into three groups(n=6 per group):DHCA group,DHCA+ulinastatin group(50000 U/kg),and DHCA+sivelestat sodium group(10 mg/kg).The respective drugs were administered via the reservoir at the beginning of cardiopulmonary bypass(CPB)and during the rewarming stage.Arterial blood gas analysis was performed the following time points:post-anesthesia induction(T1),10 min post-CPB initiation(T2),rewarm-ing(T3),immediately post-CPB(T4),and 4 h post-CPB(T5).Serum levels of interleukin-6(IL-6),IL-10,tumor necrosis factor(TNF)-α,elastase(ELA),creatinine(Cr),blood urea nitrogen(BUN),alanine aminotransferase(ALT),and aspartate aminotrans-ferase(AST)were measured at T2,T4,and T5.Hepatic and renal tissues were examined via optical microscope post-experiment.Results In DHCA rats,IL-6,TNF-α,and ELA levels progressively increased after circulatory recovery.Compared to the DHCA group,both sivelestat sodium and ulinastatin significantly reduced IL-6,TNF-α,and ELA levels while promoting IL-10 release at T5(all P<0.05).The sivelestat sodium group exhibited significantly lower TNF-α(P=0.026)and ELA(P=0.012)levels at T5 than the ulinastatin group.Cr,BUN,AST,and ALT levels in the DHCA group were significantly higher than those in the siveles-tat sodium and ulinastatin groups at T5(all P<0.01).The sivelestat sodium group exhibited lower Cr,AST,ALT,and histopatho-logical scores for hepatic/renal tissues than the ulinastatin group(all P<0.05).Sivelestat sodium attenuated renal tubular injury and reduced hepatocellular vacuolization.Conclusion Sivelestat sodium mitigates DHCA-induced inflammatory responses by suppressing IL-6,TNF-α,and ELA levels while promoting IL-10 elevation.Compared to ulinastatin,it is more effective in miti-gating acute hepatic and renal injury,indicating significant hepatorenal protective effects.