Objective:To explore the effects of protocatechuic acid on lipid metabolism and mitogen-activated protein kinase(MAPK)pathway in hyperlipidemia rats.Method:SD rats were randomly divided into control group,high fat model group,positive drug control group(positive group),low dose protocatechuic acid group(low PCA group)and high dose protocatechuic acid group(high PCA group)according to random number table,with 10 rats in each group.The rats in the control group were fed a basal control diet,while the rats in the model group,positive group,low PCA group,and high PCA group were fed a 45%high-fat diet for modeling.At the 3rd week of modeling,rats in the positive group were administered daily with atorvastatin calcium solvent(5 mg/kg).The rats in the low PCA group and high PCA group were given PCA solvent 100 mg/kg and 200 mg/kg daily,respectively.Rats in the control group and model group were administered the same volume of normal saline intragastrically every day,and all rats in each group received continuous medication for 4 weeks.The body weight of each group was measured weekly.At the end of the administration,1%sodium pentobarbital was injected into the abdominal cavity for anesthetization.The liver tissue and abdominal aortic blood were then separated,and serum was collected after thoracotomy.The contents of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoproteincholesterol(HDL-C)in serum of rats were detected by automatic biochemical analyzer.The contents of malonaldehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in liver and serum of rats in each group were detected by the kit,and the levels of interleukin(IL)-1β,IL-6 and TNF-αin serum were detected by the kit.The relative expression levels of cholesterol regulatory element binding protein 2(SREBP2)and 3-hy-droxy-3-methylglutaryl-coenzyme areductase(HMGCR)genes in liver tissues of each group were detected by reverse transcription-polymerase chain reaction(RT-PCR).The expression levels of SREBP2,HMGCR,p38MAPK,phosphorylated p38MAPK(p-p38MAPK),extracellular signal-regulated kinase(ERK),phosphorylated ERK(p-ERK),JNK,and p-JNK in rat liver tissues of each group were detected by Western Blot.The pathological changes of rat liver tissue in each group were detected by hematoxylin-eosin(HE)staining.Result:Compared with control group,liver index and the levels of TC,TG,LDL-C,MDA,IL-1β,IL-6,and TNF-αin model group,positive group,low PCA group and high PCA group increased(P<0.05),while the levels of HDL-C,SOD,and GSH-Px decreased(P<0.05).Compared with model group,liver index and the levels of TC,TG,LDL-C,MDA,IL-1β,IL-6,and TNF-α in positive group,low PCA group,and high PCA group decreased(P<0.05),while the levels of HDL-C,SOD,and GSH-Px increased(P<0.05).Compared with the control group,the mRNA and protein expression levels of HMGCR and SREBP2 in liver tissues of model,positive,low PCA,and high PCA groups were increased(P<0.05),and the protein phosphorylation levels of p38MAPK,ERK,and JNK were increased(P<0.05).Compared with model group,the mRNA and protein expression levels of HMGCR and SREBP2 in liver tissues of rats in positive,low PCA and high PCA groups were decreased(P<0.05),and protein phosphorylation levels of p38MAPK,ERK,and JNK were less(P<0.05).Conclusion:PCA can effectively regulate blood lipid levels in hyperlipidemia rats,inhibit oxidative stress response and inflammatory damage in liver tissue,and may regulate lipid synthesis and metabolism through MAPK signaling pathway,thus playing some role in lowering blood lipid.
hyperlipoidemiaprotocatechuic acidlipid metabolismmitogen-activated protein kinase pathwayinflammatoryexperimental study
维普
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