Objective To explore the possible mechanism of hydroxysafflor yellow A (HSYA) in alleviating liver injury in septic mice from the perspective of mitochondrial autophagy. Methods Fifty C57BL/6 mice were randomly divided into sham operation group (10 mice), sepsis group (10 mice), and HSYA group (20 mice). The sepsis model was established by cecal ligation and puncture (CLP). HSYA (120 mg·kg-1) was subcutaneously injected 24 hours, 2 hours before and 2 hours after the model establishment in the HSYA group. The survival status of each group was evaluated by the mouse sepsis scoring system. The pathological changes of liver tissue and the morphological changes of mitochondria were observed by HE staining and transmission electron microscopy, respectively. The levels of alanine aminotransferase, aspartate aminotransferase, and inflammatory factors interleukin-6, tumor necrosis factor-α, and interleukin-1β in mouse serum were detected by ELISA. The expression levels of mitochondrial autophagy-related proteins PTEN-induced putative kinase 1(PINK1), E3 ubiquitin ligase (Parkin), ubiquitin-and LC3-binding protein p62(p62), and Microtubule-Associated Protein 1 Light Chain 3 Beta-II (LC3B-II) in liver tissue were detected by Western blot. Results HSYA effectively improved the mental state, reaction speed, activity, and respiratory quality of CLP mice. Compared with the CLP group, liver injury in the HSYA group was improved, and the number of mitochondrial autophagosomes increased. The levels of ALT, AST, IL-6, TNF-α, IL-1β in serum and the mRNA levels of IL-6, TNF-α, and IL-1β in the HSYA group were all decreased. Compared with the CLP group, the expression levels of PINK1, Parkin, and LC3B-II proteins in the liver tissue of the HSYA group were increased, and the expression level of p62 protein was decreased. Conclusion HSYA can inhibit the release of inflammatory factors in septic mice and alleviate liver injury. The mechanism may be related to the regulation of mitochondrial autophagy and the PINK1/Parkin pathway.
Key words
sepsis /
liver injury /
hydroxysafflor yellow A /
mitochondrial autophagy /
PINK1/Parkin pathway
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