Study on Xuebijing Injection Inhibits NLRP3 Inflammasome Activation to Protective Effect on Liver Injury Induced by Heat-stroke in Rats

ZHU Guoguo; YAO Chen; XU Siya; YE Ming; ZHU Huali; CHEN Ying; TANG Zhongzhi; FANG Qing

doi:10.13730/j.issn.2097-2148.2024.12.002

Abstract：Objective To investigate the protective effects of Xuebijing injection on the liver of heatstroke rats and explore the underlying mechanisms.Methods A total of 24 SPF SD rats were randomly divided into normal control group,heatstroke group and Xuebijing treatment group,with 8 rats in each.In the normal control group,the anesthe-tized rats were placed in 26 ℃ environment without any treatment until the end of the experiment;the rats in the heat-stroke group were pretreated with normal saline(4ml/kg,tail vein injection)and the heatstroke model was established,after successful modeling,the rats were transferred to the environment of 22-25 ℃ and recovered for 6 h;the rats in the Xuebijing treatment group were pretreated with Xuebijing injection(4 ml/kg,tail vein in-jection)for heatstroke modeling,after successful model-ing,the rats were transferred to the environment of 22-25 ℃ and recovered for 6 h.After reaching the predetermined time,blood samples of rats were collected from the aorta abdominals,and the levels of inflammatory factors interleukin 1 beta(IL-1β),interleukin 18(IL-18),interleukin 6(IL-6),tumor necrosis factor alpha(TNF-α)and high mobility group proteins B1(HMGB1)in serum were measured by enzyme-linked immunosorbent assay(ELISA).The levels of nucleo-tide oligomerization domain like receptor hot protein domain related proteins 3(NLRP3),Caspase1,apoptosis related speckled protein(ASC)and myeloperoxidase(MPO)in liver tissue were determined by quantitative polymerase chain re-action(qPCR).Additionally,hematoxylin-eosin staining was performed to observe the pathological changes in liver tis-sue,and the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum of rats were meas-ured.Results The levels of serum inflammatory factors TNF-α,IL-6,IL-1β and IL-18,the expression levels of HMGB1 in serum and liver,and the relative mRNA expression levels of NLRP3,Caspase1 and ASC in liver tissue,the MPO level in hepatocytes,and the contents of ALT and AST in serum of rats in the heatstroke group were significantly higher than those in normal control group(all P＜0.05);the structure of the hepatic lobules was disordered,central venous conges-tion and thrombus were present,hepatocyte edema and fat granules appeared,and hepatocyte necrosis was widespread.But the levels of inflammatory factors TNF-α,IL-6,IL-1β,IL-18,ALT and AST in serum,the expression levels of HMGB1 in serum and liver,the level of MPO in hepatocytes of Xuebijing treatment group were significantly lower than those in heatstroke group(all P＜0.05),only hepatocytes were edematous and the hepatic lobules were well structured.Conclusion Xuebijing injection has a protective effect on inflammatory response and liver damage in heatstroke rats,and its mechanism may be related to the inhibition of NLRP3 inflammasome activation.