A Preliminary Study On The Protective Effect And Mechanism Of Magnesium Isoglyrrhizinate On Multi-organ Function In Mice With Sepsis

Objective:Investigate the protective effect of magnesium isoglyclycinate on multi-organ function in mice with sepsis,and to investigate the effect of magnesium isoglyrrhizinate on pyroptosis signaling pathway.Methods:Eight-week-old male Balb/C mice were randomly assigned to six groups: sham surgery + solvent control group(Sham+V),sham surgery + magnesium isoglyrrhizinate group(Sham+Mg IG),6h sepsis model + solvent control group(6h CLP+V),6-hour sepsis model +magnesium isoglyrrhizinate group(6h CLP + Mg IG),24 h sepsis model +solvent control group(24h CLP + V),24 h sepsis model + magnesium isoglyrrhizinate group(24h CLP + Mg IG).A sepsis model was established using cecum ligation and puncture(CLP).Magnesium isoglyrrhizinate intervened with intraperitoneal injection of magnesium isoglyrrhizinate injection(50 mg/kg)immediately after sham surgery or molding,and was supplemented once 3 hours,and an equal amount of 0.9% Na Cl injection was given.The serum and heart,liver,lung and kidney tissues of mice were collected at 6 hours and 24 hours after surgery,and the tissues of various organs were treated with hematoxylin-eosin staining,and the lung tissue,liver tissue,myocardial tissue and kidney tissue of each group of mice were observed under light microscopy Pathological changes to assess organ pathological damage;fully automated analyzer to detect alanine transaminases(ALT),aspartate aminotransferase(AST),creatinine(SCR),Urea nitrogen(BUN),lactate dehydrogenase(LDH),creatine kinase isoenzyme(CK-MB)levels,enzyme-linked immunosorbent assay(ELISA)The serum tumor necrosis factor α(TNF-α),interleukin-1 β(IL-1 β),and interleukin-6(IL-6)levels in mice were measured Serum malondialdehyde(MDA)levels and superoxide dismutase(SOD)activity were detected by colorimetric method.Western blot was used to detect the expression of Caspase-11,GSDMD,IL-1 β in liver,kidney and lung tissues,and the effect of magnesium isoglyrrhizinate on the cytojectrosis signaling pathway of various organs was observed.outcome :Sham+V Compared to 6h and 24 h CLP+V Mice had an increased liver,kidney,and lung tissue injury score(P<0.01),serum ALT、AST、BUN、LDH、CK-MB indicator rise(P<0.05),serum SOD activity descent(P<0.01),MDS level rise(P<0.05),TNF-α、IL-6、IL-1β level rise(P<0.01,P < 0.05);After intervention with magnesium isoglyrrhizinate,6h and 24 h CLP+Mg IG group liver,kidney,lung tissue in mice pathology rating drop(P<0.01),serum ALT、AST、LDH、CK-MB、BUN、SCR indicator drop(P<0.01),Serum SOD activity descent(P<0.01),MDA decreased level(P<0.01),TNF-α、IL-1β、IL-6 decreased level(P<0.01);In Western blot,24 h CLP+V in mouse liver,lung tissue and kidney tissue Caspase-11、GSDMD、IL-1β protein expression increased significantly compared with Sham+V mice(P<0.05,P<0.01),compared with mice in the 24 h CLP+V group,24 h CLP+Mg IG group Mice The expression of the above protein decreased significantly(P<0.05,P<0.01)。Conclusion:Magnesium isoglyrrhizinate injection has a protective effect on the multi-organ function of mice with sepsis,and its mechanism may be related to the anti-inflammatory and antioxidant effect of magnesium isoglyrrhizinate,and the expression of pyroptosis-related protein Caspase-11 and GSDMD in the liver,lung tissue and kidney tissue of mice with sepsis can be reduced and the expression of inflammatory mediator IL-1β can be reduced.