Experimental Study on the Regulation of Autophagy and Apoptosis by Jinzhi in Repairing Intestinal Mucosal Damage in Septic Mice
Objective To investigate the protective effect and mechanism of Jinzhi on intestinal mucosa of sep-tic mice by regulating autophagy and apoptosis.Methods Fifty healthy SPF BALB/c mice were adaptively fed for 3 days,and then divided into control group(n=10)and model group(n=40).The sepsis model was estab-lished by cecal ligation and puncture(CLP)method in model group.After successful preparation,the mice were randomly divided into CLP group,CLP+normal saline(NS)group,CLP+Jinzhi group,and CLP+Jinzhi+NF-κB inhibitor(PDTC)group.The mice in the CLP+NS group were given normal saline(0.01 mL·g-1)by gavage,and the mice in the CLP+Jinzhi group were given Jinzhi(0.01 mL·g-1)by gavage.The CLP+Jinzhi+PDTC group was treated with Jinzhi(0.01 mL·g-1)and injected with PDTC(120 mg·kg-1).Intragastric administration was performed at 12 h,24 h and 36 h after grouping.Intestinal tissue and serum were collected at 48 h.HE staining was used to observe the morphological changes of the intestine.ELISA was used to measure the levels of TNF-α,IL-6 and IL-1β in serum.The mRNA and protein expressions of LC3Ⅰ,LC3Ⅱ,Caspase 3 and Cas-pase 8 in the small intestine were detected by RT-qPCR and Western blot,respectively.Results In contrast to the control group,the mice in CLP group had a high number of necrotic intestinal mucosal epithelial cells,var-ied degrees of intestinal mucosal villi swelling,and a large number of inflammatory cells infiltrating the submu-cosa.The expression levels of TNF-α,IL-6,and IL-1β in serum(P all<0.05)and the protein and mRNA expression levels of LC3Ⅰ、LC3Ⅱ,Caspase 3,and Caspase 8 in small intestine were significantly increased(P all<0.05).Compared with the CLP group,there was no significant difference in the above indicators in the CLP+NS group,but the above indicators in the CLP+Jinzhi group and the CLP+Jinzhi+PDTC group were significantly improved,and the CLP+Jinzhi+PDTC group had better effects.Conclusion Jinzhi could improve intestinal mucosal injury in septic mice through inhibiting the expression of autophagy-related proteins LC3Ⅰ,LC3Ⅱand apoptosis-related proteins Caspase 3 and Caspase 8,decreasing the levels of TNF-α,IL-1β,and IL-6,and inhibiting the inflammatory response of the organism,thus playing a therapeutic role.
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维普
