Study On The Mechanism Of Salidroside On Acute Liver Injury Induced By Lipopolysaccharide In Septic Mice

Salidroside is the main active ingredient of Rhodiola crenulata(Hook.f.et Toms.)H.Ohba,and its main pharmacological effects are anti-hypoxia,anti-inflammation,anti-tumor and so on.At present,the study of salidroside on liver injury is mainly focused on chemical liver injury caused by environment,diet and drug side effects,while there are few studies on acute liver injury caused by sepsis.In this study,salidroside was applied to LPS induced liver injury in mice to explore its protective mechanism and provide relevant basis for the development of related drugs for the prevention of acute liver injury caused by sepsis.In this experiment,80 C57BL/6 mice were divided into Control group,LPS group,salidroside low dose group(Group L),salidroside middle dose group(Group M)and salidroside high dose group(Group H).According to the pre-administration mode,the doses of 30mg/kg,60mg/kg and 120 mg kg,respectively.Control group and LPS group were all injected with 0.9%Na Cl injection of the same volume in Group L,Group M and Group H respectively.Salidroside was administered intraperitoneally for 14 days,once a day.The model was made 24 hours after administration on the 14 th day,in which the blank control group did not make the model,and each mouse in the other 4 groups was injected intraperitoneally with LPS 5mg/kg to make sepsis model.After fasting,the mice were given salidroside for the last time one hour after modeling.Group L,Group M and Group H were all injected with salidroside of the previous dose,while Control group and LPS group were injected with 0.9% sodium chloride injection of the same volume.After 12 hours of modeling,the blood of the mice was collected by the method of enucleating eyeballs and taking blood,then the mice were anesthetized and the liver was removed.Through the comparison of liver index,the liver pathological changes of mice were observed,and the pathological sections of liver tissue of mice were observed,combined with the determination of serum AST and ALT to determine the hepatoprotective effect of salidroside.The m RNA expression of IL-1β and IL-6 in liver tissue was determined by q PCR,the levels of IL-1β and TNF-α in liver tissue were measured by ELISA,and the protein expression of NLRP3 was determined by Western Blot.The hepatoprotective effect of salidroside was proved by molecular mechanism.The results of this thesis are as follows:Compared with the Control Group,the liver index of the LPS Group decreased significantly(P < 0.05),and there was a significant difference between the three groups and the LPS group(P < 0.05),and the improvement effect of H Group was the best(P<0.01).Compared with Control Group,the levels of serum AST and ALT in LPS group increased significantly(P < 0.001),and the levels of serum AST and ALT in three groups decreased significantly compared with LPS group,among which Group H had the best effect(P < 0.001).Salidroside can improve the 7-day survival rate of septic mice.The survival rate of Group H was 75% higher than that of LPS Group.Compared with Control group,the m RNA expression levels of IL-1βand IL-6 in LPS group were significantly higher than those in LPS group(P< 0.001).Compared with LPS group,the m RNA expression of IL-1β and IL-6 in Group L,Group M and Group H decreased significantly,especially in Group H(P < 0.001).Compared with Control group,the level of IL-1β and TNF-α in liver tissue of LPS group increased significantly(P < 0.001).Compared with LPS group,the levels of IL-1β and TNF-α in liver tissue of H group decreased significantly(P < 0.01).The results of Western Blot showed that the relative expression of NLRP3 in LPS Group was significantly higher than that in Control Group(P<0.05),and the relative expression of NLRP3 in Group H was significantly lower than that in LPS Group(P < 0.001).Conclusion: During the progression of sepsis,inflammatory factors are widely activated,causing acute damage to the liver of mice.Salidroside has hepatoprotective effect on LPS-induced acute liver injury in septic mice and can improve the survival rate of septic mice.Its anti-inflammatory mechanism may be achieved by inhibiting the transmission of NLPR3 pathway and down-regulating the level of inflammatory factors.