Based On The SREBP-1c-FAS Approach, The Mechanism Of Xiaoyao San's Effect On Lipid Metabolism In Rats With Depression Of Liver-stagnation And Spleen-deficiency Type Was Explored

Research backgroundDepression is a kind of mental disease caused by complex and multiple factors.It has the characteristics of high morbidity,high recurrence rate and high suicide rate.There are more than 350 million patients with depression in the world,and the prevalence rate of depression in China is 3%～5%.At present,the molecular mechanism of Xiaoyaosan in the treatment of depression is not completely clear.Depression patients are often accompanied by obvious abnormal energy metabolism such as obesity or marasmus,abnormal appetite.The lipogene-sis and steatolysis of body are mainly carried out in peripheral organs such as liver and adi-pose tissue.It is particularly important and necessary to study the effect of traditional Chinese medicine compound on lipometabolism in peripheral organs.Sterol regulatory element bind-ing protein(SREBP-1c)participates in de novo synthesis of fatty acid in hepatocytes by reg-ulating downstream target gene fatty acid synthase.SREBP-1c,also known as adipocyte de-termination and differentiation factor-1(ADD1),is involved in regulating the synthesis of fatty acids and TG,as well as the expression of glucose metabolism-related enzyme genes,which are highly expressed in liver tissues.In addition,the process of lipid accumulation is also a process of increasing the volume of mature adipocytes,which is related to the expres-sion of genes related to lipid synthesis(TG,fatty acid synthesis).Previous experimental stud-ies have found that by replicating the rat model of depression with stagnation of liver qi and spleen deficiency syndrome induced by chronic unpredictable mild stress(CUMS),abnormal expression of lipometabolism was found in the depression model rats with stagnation of liver qi and spleen deficiency syndrome.At the same time,document studies have found that Xiaoyaosan had a good regulatory effect on depression induced by CUMS,and its mechanism may be related to the regulation of abnormal expression of lipometabolism,but whether Xiaoyaosan plays a role in the treatment of depression by activating the SREBP-1c/FAS sig-naling pathway remains to be confirmed.Research purposeTo observe the expression of SREBP-lc-FAS gene in liver of rats with stagnation of liver qi and spleen deficiency syndrome and the regulatory effect of Xiaoyaosan,in order to ex-plore the molecular biological basis of abnormal lipid metabolism in stagnation of liver qi and spleen deficiency syndrome,and to provide new ideas for the study of biological basis of stagnation of liver qi and spleen deficiency syndrome.MethodsSix-week chronic unpredictable mild stress(CUMS)method was used to replicate the rat model of depression with stagnation of liver qi and spleen deficiency syndrome.The general state,weight and behavior detection of the experimental rats(sucrose preference test,open field test)were evaluated.HE staining was used to observe the pathological changes of liver.The expression of TC,TG,HDL and LDL in serum was detected by automatic biochemical analyzer,and the regulating effect of xiaoyaosan was observed.The changes of SREBP-1c and FAS mRNA in rat liver tissues were detected by RT-PCR and the regulatory effect of Xiaoyaosan was observed.ResultsThe rat model of depression with stagnation of liver qi and spleen deficiency syndrome was successfully replicated,and depression was relatively reduced after the intervention of Xiaoyaosan and fluoxetine.The results of HE staining showed that the liver tissue of normal rats was complete,and the cells were arranged neatly,without obvious swelling and defor-mation.In the model group,the liver tissue structure presented different degrees of disorder,and the number of different lipid droplets vacuoles could be seen in the cells.Compared with the model group,the pathological changes of liver tissue in Xiaoyaosangroup were alleviated and tended to normal group,and some lipid vacuoles still existed in fluoxetine group.Bio-chemical results showed that the expression of HDL in the model group decreased signifi-cantly compared with the normal group(P<0.01).After the intervention of Xiaoyaosan and fluoxetine,the content of HDL in the peripheral serum of the model group increased(P<0.01,P<0.05);the content of LDL in the peripheral serum of the model group increased compared with the normal group(P<0.05),and Xiaoyaosan also showed a regulatory effect and reduced the expression of LDL in the serum(P<0.01).Compared with the normal group,the expres-sion of TG increased in the model group(P<0.05),but decreased significantly after the inter-vention of Xiaoyaosan(P<0.01).There was no significant difference in TC between the two groups(P>0.05).The results of PCR showed that the expression of SREBP-1c mRNA in rat liver of the model group was significantly up-regulated,and the expression of FAS mRNA was significantly up-regulated compared with the normal group(P<0.01,P<0.01).Compared with the model group,Xiaoyaosan could significantly down-regulate the expressions of srebp-1c mRNA and FAS mRNA in rat liver after intervention in the model group(P<0.05).Compared with the normal group,SREBP-lc mRNA expression of rats in the fluoxetine in-tervention model group was significantly up-regulated(P<0.01),while FAS mRNA expres-sion was not statistically significant.Conclusions1.CUMS can successfully reproduce the rat model of depression with stagnation of liver qi and spleen deficiency syndrome.2.Xiaoyaosan has a good anti-depression effect,which can reduce the liver lipid content of depressive rats in different degrees.3.Xiaoyaosan can down-regulate the expression of SREBP-lc and FAS in rat liver tissue.SREBP-lc and FAS may be a promising target for Xiaoyaosan to prevent and treat depression.Its antidepressant mechanism is to activate the expression of SREBP-1c and FAS,but the detailed mechanism still needs further study and discussion.