Study on the mechanism of inhibiting liver tissue apoptosis by 4-phenylbutyrate sodium salt and alleviating liver injury in sepsis
Objective To investigate the protective effect of 4-phenylbutyrate(4-PBA)on liver apoptosis in septic mice and its signaling mechanism.Methods The mice were randomly divided into 3 groups:Sham operation group(Sham group),sepsis group(model group,LPS group),and experimental group(treatment group,LPS+4-PBA group).At 24h after LPS,the general condition,sepsis severity score,liver function,liver tissue inflammation index and liver tissue apoptosis degree of mice in each group were ob-served.Western blot was used to detect the expression levels of apoptosis-related proteins Bax,Bcl-2 and endoplasmic reticulum stress-related proteins ATF4 and CHOP.Results The severity scores of sepsis in LPS group and LPS+4-PBA group were significantly higher than those in Sham group,and those in LPS+4-PBA group were lower than those in LPS group(P<0.05).ALT[(395.10±93.08)IU/L]and AST[(625.50±63.68)IU/L],the apoptotic index(0.0209±0.0041),the levels of IL-6(9406±674),TNF-α(822.30±229.10)and IL-1β(10.58±0.14)in LPS group were significantly higher than those in Sham group.After treatment with 4-PBA,the above indexes of septic mice significantly decreased,and the differences were statistically significant(P<0.05).The results of apopto-sis level of related proteins in liver tissue of mice in each group showed that the expression of apoptosis-related protein caspase-3 could be significantly reduced after pre-administration of 4-PBA.The results showed that pretreatment with 4-PBA significantly reduced the protein expression of endoplasmic reticulum stress pathway-related proteins ATF-4 and CHOP in liver tissues of septic mice.Conclusions 4-PBA can inhibit the apoptosis of liver tissue in septic mice by inhibiting ATF-4/CHOP signaling pathway,thus alle-viating sepsis-induced liver injury.
4-PBAsepsisendoplasmic reticulum stressapoptosis of cells
国家科技期刊平台
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