4- 苯基丁酸钠盐抑制肝组织凋亡减轻脓毒症肝损伤的机制研究

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Abstract 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 observed. 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 apoptosis 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 alleviating sepsis-induced liver injury.

Key words： 4-PBA sepsis endoplasmic reticulum stress apoptosis of cells

Received: 16 October 2023

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	FU Jingnan
	ZHOU Li

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FU Jingnan,ZHOU Li. Study on the mechanism of inhibiting liver tissue apoptosis by 4-phenylbutyrate sodium salt and alleviating liver injury in sepsis[J]. Med. J. Chin. Peop. Armed Poli. Forc., 2024, 35(8): 667-671.

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https://journal08.magtechjournal.com/Jwk_wjyx/EN/ OR https://journal08.magtechjournal.com/Jwk_wjyx/EN/Y2024/V35/I8/667

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