OBJECTIVE

2

To explore the mechanism of modified Xianfang huoming decoction in the treatment of sepsis-induced liver injury from the perspective of gut microbiota and metabolites.

METHODS

2

Sixty SD rats were divided into blank group （normal saline）， model group （normal saline）， positive control drug group （Dexamethasone tablet， 5.0 mg/kg）， modified Xianfang huoming decoction high-dose， middle-dose and low-dose groups （6.0， 3.0， 1.5 g/kg， calculated by crude drug） according to equilibrium-partitioning approach of body mass， with 10 rats in each group. They were given relevant drug/normal saline 10 mL/kg， once a day， for consecutive 14 days. After the last medication， except for blank group， other groups were given intraperitoneal injection of lipopolysaccharide 10 mg/kg to induce sepsis model. Twelve hours after modeling， serum levels of inflammatory indexes in rats [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] and liver function indicators [total cholesterol （TC）， triglyceride （TG）， aspartate transaminase （AST）， alanine transaminase （ALT）] were detected. The changes of gut microbiota and liver metabolites in rats were analyzed by 16S rRNA technology and liver metabolomics.

RESULTS

2

Modified Xianfang huoming decoction could significantly improve the indexes of serum inflammatory indexes and liver function in rats with sepsis-induced liver injury （

P

＜0.05 or

P

＜0.01）； there was a significant callback effect on the relative abundance of 11 genera of bacteria （such as

Akkermansia

，

Lactobacillus

and

Bilophila

） among the 5 dominant phyla（

P

＜0.05 or

P

＜0.01）. Twelve metabolites related to liver injury caused by sepsis were identified， such as glycine cholic acid， phosphatidylcholine， taurine （

P

＜0.05 or

P

＜0.01）， mainly involving glycerol phospholipid metabolism， purine metabolism and primary bile acid metabolism.

CONCLUSIONS

2

Modified Xianfang huoming decoction can improve liver injury induced by sepsis by regulating gut microbiota and liver metabolites.