The Effect and Mechanism of Xiangsha Liujunzi Decoction on Liver Endoplasmic Reticu-lum Stress/PERK/SREBP1c Pathway and TG Synthesis in Spleen Deficiency Hyperlipi-demia Rats
Objective To explore the effect and mechanism of Xiangsha Liujunzi Decoction on liver endoplasmic reticulum stress/PERK/SREBP1c pathway and TG synthesis in spleen deficiency hyperlipidemia rats.Methods 24 SPF SD rats were randomly divided into blank control group,hyperlipidemia model group,spleen deficiency hyperlipidemia group and Xiangsha Liujunzi de-coction group with 6 rats in each group.The spleen deficiency model was established by diet and exhaustive swimming in the spleen deficiency high fat group and Xiangsha Liujunzi decoction group.Except for the blank control group,the other groups were fed with high-fat diet and began to be gavaged at the 10th week.The Xiangsha Liujunzi decoction group was given 11.34g/(kg·d),and the other groups were given the same volume of normal saline for 4 weeks.The level of blood lipid was detected by au-tomatic biochemical analyzer,the pathological changes of liver were observed by HE staining,the lipid deposition of liver was ob-served by oil red O staining,the level of TG in liver tissue was detected by microplate method,the expression level of GRP78,SREBP-1c and ACC1mRNA in liver tissue was detected by RT-qPCR method,and the expression level of PERK,p-PERK,GRP78,SREBP-1c and ACC1 protein in liver tissue was detected by Western blotting method.Results Compared with the blank control group,the serum levels of TC,TG and LDL-C in the hyperlipidemia model group and spleen deficiency hyperlipi-demia group increased significantly,while the level of HDL-C decreased significantly(P＜0.05or P＜0.01),and the cyto-plasmic porosity in hepatocytes was reticular,fat vacuoles were obvious,orange lipid droplets were obvious and diffuse distribu-tion.The level of TG(P＜0.01),GRP78,SREBP-1c,ACC1mRNA and protein expression in liver tissue were significantly increased(P＜0.05or P＜0.01),and the relative expression level of p-PERK protein was significantly increased(P＜0.05).Compared with the hyperlipidemia model group,the level of serum TC in the spleen deficiency and hyperlipidemia group increased significantly,the level of HDL-C decreased significantly(P＜0.05),the levels of TG and LDL-C tended to in-crease,the level of TG in liver tissue increased significantly(P＜0.01),the expression of GRP78,SREBP-1c,ACC1mRNA and protein increased significantly(P＜0.05or P＜0.01),and the expression of p-PERK protein increased significantly(P＜0.05).Compared with the spleen deficiency and hyperlipidemia group,the levels of serum TC,TG and LDL-C in Xiangsha Li-ujunzi decoction group decreased significantly,while the level of HDL-C increased significantly(P＜0.01),the degree of cyto-plasmic loosening of hepatocytes decreased,fat vacuoles and orange lipid droplets decreased significantly.The level of TG,the expression of GRP78,SREBP-1c,ACC1mRNA and protein,and the expression of p-PERK protein in liver tissue decreased significantly(P＜0.01).Conclusion Xiangsha Liujunzi decoction may reduce the occurrence of liver lipid deposition in rats with spleen deficiency and hyperlipidemia by improving endoplasmic reticulum stress/PERK/SREBP1c pathway and affecting triglycer-ide synthesis related protein.
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