Regulatory Effect Of Glycyrrhizic Acid On Inflammatory Response In Septic Mouse Model

Objective: sepsis is a disorder of host response caused by infection,leading to the organ dysfunction which treats to life.The immune mechanism of sepsis is complex,through the unremitting efforts of a large number of scholars at home and abroad,people have a more comprehensive understanding of the immune mechanism of sepsis in recent years.At present,it is generally believed that the immune dysfunction of sepsis is mainly characterized by the imbalance of pro-inflammatory / anti-inflammatory response.And these immune cells and cytokines have become the new targets for the treatment of sepsis in recent years.Licorice is a traditional Chinese herbal medicine in China and Southeast Asia.Glycyrrhizic acid(Glycyrrhizic Acid GAA)is a kind of active substance extracted from the root of Glycyrrhiza uralensis.It is a triterpenoid compound with many pharmacological activities.The aim of this study was to explore the role of glycyrrhizic acid in regulating the inflammatory response of sepsis in septic mice by using the immunomodulatory effect of glycyrrhizic acid(glycyrrhizic acid).Basic research content is: this study mainly adopts the method of random control.The injury of renal tubules,the apoptosis of macrophages in peritoneal lavage fluid,and the concentrations levels of IL-1 ?,TNF-a and HMGB1 in blood were compared in different treatment groups to explore the regulatory effect of glycyrrhizic acid on the immune function of sepsis in mice and its possible mechanism.Research methods are: sepsis mouse model was established by cecal Ligation and uncture.The mice were randomly divided into 5 groups.Sham-operation + drug group,surgery + placebo group,surgery + high-dose drug group(25.9ml / kg),surgery + medium-dose drug group(12.95 ml / kg)and surgery + low-dose drug group(6.475 ml / kg).with 10 rats in each group.Different drugs were given immediately after operation.Four hours after drug intervention,blood samples were taken from mice eyeball,serum was isolated,and the concentration of IL-1 ?-TNF-a HMGB1 in serum was detected and compared with statistical method.The mice were killed by cervical dislocations and perfused with normal saline.The peritoneal lavage fluid was used to analyze the apoptosis of macrophages by flow cytometry.The bilateral renal tissues were taken and immediately fixed in the 4% of formalin and sectioned with paraffin embedded.Pathological sections were stained with HE,and renal tubular injury in septic mice was observed under microscope,and the scores of different groups were compared by non-parametric rank sum test after scoring.The results of the study is as follows: 1.In the pathological sections of kidney tissues of mice,the score of sham-operation + placebo group was lower than that of operation + placebo group.The score of the treatment group decreased in a dose-dependent manner with the intervention of glycyrrhizic acid.Operation + placebo group > operation + low dose group > operation + medium dose group > operation + high dose group > sham operation + placebo group.2.The results of flow cytometry showed that the apoptosis rate of peritoneal macrophages in the operation + placebo group was higher than that in the sham operation + placebo group(92.23% and 22.21)(P < 0.05).The apoptosis of macrophages was alleviated in the group of operation + low dose drug(P < 0.05).In the operation + medium dose group,78.73 and 78.73,P < 0.05;Operation + high dose drug group 77.54%(P < 0.05).3.The mean value of IL-1 ? in the sham-operation + placebo group was 0.217 pg / ml.The operation + placebo group had the highest mean value of 0.372 pg/ml.There was a statistical difference between two groups(P < 0.001).In the same comparison,the mean value of serum TNF-a in the sham-operation + placebo group was 0.432 pg / ml,the lowest in the five groups.The operative + placebo group had the highest mean value of 0.831 PG / ml,and there was a statistical difference between the two groups(P < 0.001).Compared with the serum concentration of HMGB1 in the five groups,the level of HMGB1 in the sham-operation + placebo group was the lowest,with an average value of 213.931 PG / ml.The operative + placebo group had the highest mean value of 498.056 PG / ml,and there was a statistical difference between the two groups(P < 0.001).Further statistical analysis showed that the concentration of three cytokines in the operation + treatment group was lower than that in the operation + placebo group(P < 0.01).Conclusion: 1.Glycyrrhizic acid has a protective effect on renal tubular epithelial cells in the septic mice.2.Glycyrrhizic acid can reduce the apoptosis of peritoneal macrophages in the septic mice.3.Glycyrrhizic acid could inhibit the secretion of cytokines in septic mice in a dose-dependent manner.