Regulatory Mechanism of Xiaozheng Tongluo Method on Hepatic Lipid Metabolism in ApoE-/- Mice: Insights from the Sterol Regulatory Element-binding Protein-2/3-hydroxy-3-methylglutaryl Coenzyme A Reductase/Low-density Lipoprotein Receptor Signaling Pathway

Abstract

Objective: The objective of the study was to explore the regulatory mechanism of the Xiaozheng Tongluo method on lipid metabolism in liver tissue based on the sterol regulatory element-binding protein-2/(SREBP2)/3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR)/low-density lipoprotein receptor (LDLR) signaling pathway. Materials and Methods: C57BL/6 mice were selected as the blank group. The apolipoprotein E-deficient (ApoE-/-) mice were randomly divided into the model group, traditional Chinese medicine (TCM) group, and control group. The general condition of the mice was determined by the mouse’s state and liver weight. Liver hematoxylin and eosin staining and Oil Red O staining were used to observe the pathological changes and lipid droplet deposition of the liver. The protein expression levels of SREBP2, HMGCR, and LDLR were detected by Western blotting and polymerase chain reaction. Results: (1) The rats in the model group were in poor condition, and their liver weight increased significantly. Compared with the model group, the condition of the TCM group and the control group improved to varying degrees, and their liver weight decreased significantly. (2) Compared with the normal group, the hepatocytes in the model group were arranged in a disorderly manner, and the red-stained lipids of stem cells increased significantly. Compared with the model group, the degree of liver lesions in the control group and TCM group was reduced, and the red-stained lipid of hepatocytes was significantly reduced. (3) Compared with the blank group, the expression of SREBP2 and HMGCR protein in the model group increased significantly, and the expression of LDLR protein decreased significantly (P < 0.05). Compared with the model group, the expression of SREBP2 and HMGCR protein in the TCM group decreased significantly, and the expression of LDLR protein increased significantly (P < 0.05). Conclusions: The method detailed in this paper can increase the expression of SREBP2 and HMGCR protein and decrease the expression of LDLR protein, thus regulating liver cholesterol metabolism and delaying the progression of atherosclerosis.

Keywords

• apoe-/-mice
• lipid metabolism
• liver
• sterol regulatory element-binding protein-2/3-hydroxy-3-methylglutaryl coenzyme a reductase/low-density lipoprotein receptor signaling pathway
• xiaozheng tongluo method