加味香砂六君子汤对脾虚高脂血症大鼠肝组织GPR146/ERK/SREBP2信号通路的影响OA

Objective To investigate the effect of Jiawei Xiangsha Liujunzi Decoction(加味香砂六君子汤,JXLD)on the GPR146/ERK/SREBP2 signaling pathway in liver tissue of spleen-deficiency hyperlipidemia rats.Methods Seventy SD rats were divided into the Control group,high-fat Model group,spleen deficiency and high-fat(px-Model)group,low/medium/high-dose JXLD(JXLD-L/M/H)groups,and the rosuvastatin(R)group.The spleen deficiency model was established by irregular diet plus exhaustive swimming,fol-lowed by feeding with a high-fat diet(HFD)for 10 weeks to establish the hyperlipidemia model.After 8 weeks of intragastric administra-tion,serum lipid levels were measured in all seven groups.HE and oil red O staining were performed.Liver tissue total cholesterol(TC)levels were measured using a microplate assay.The mRNA levels of GPR146,PKA,SREBP2,HMGCR,and VLDL-R in liver tissue were detected by RT-qPCR.The expression levels of the corresponding proteins(GPR146,PKA,SREBP2,HMGCR,VLDL-R)as well as ERK1/2 and p-ERK1/2 proteins were detected by Western blot(WB).Results Compared with the Control group,serum lipid levels were increased in both the Model and px-Model groups.Hepatocytes were swollen and showed prominent orange lipid droplets.Liver tissue TC levels were elevated.The mRNA and protein expression levels of GPR146,PKA,SREBP2,and HMGCR were increased.The expression of p-ERK1/2 protein was upregulated,while the expression of VLDL-R mRNA and protein was decreased in these groups(P<0.05,P<0.01).Compared with the Model group,these alterations were aggravated in the px-Model group.Com-pared with the px-Model group,the treatment groups(JXLD-L/M/H/R)exhibited amelioration of these alterations,with the JXLD-H group showing the most pronounced effects.Conclusion JXLD prevented liver lipid deposition in spleen-deficiency hyperlipidemia rats.This effect may be associated with the inhibition of cholesterol synthesis through regulation of the GPR146/ERK/SREBP2 signaling path-way.