| Objective: To investigate the effects of cholic acid on glucose and lipid metabolism and inflammation in rats with metaflammation,and to reveal the regulatory mechanism of cholic acid on metaflammation,so as to provide experimental basis for the study of new drugs to prevent and treat of metaflammation for pets.Methods: SD rats fed with high fat diet for 60 days were used to establish metabolic inflammation model,and SD rats fed with basic diet were used as control.The rats were divided into five groups: model group,high-dose,medium-dose,and low-dose cholic acid groups,and negative control group.The glucose tolerance and insulin tolerance were detected on the first and third day after drug withdrawal.The serum of rats was taken on the fifth day after drug withdrawal.The activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),albumin(ALB),total protein(TP),cholesterol(CHO),high density lipoprotein(HDL),low density lipoprotein(LDL),triglyceride(TG)were detected by automatic biochemical analyzer free fatty acid(FFA)and total bile acid(TBA)were detected by biochemical kit;monocyte chemoattractant factor-1(MCP-1),interleukin-6(IL-6)and interleukin-1 β(IL-1β)were detected by ELISA kit;macrophage inflammatory protein-1 α(MIP-1α),interleukin-10(IL-10),interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)were detected by(real-time fluorescent quantitative PCR)The rats were killed at the end of the experiment to determine the wet weight of fat(WAT)and fat coefficient;he staining method was used to observe the pathological changes of liver tissue;immunohistochemical method was used to detect the distribution and expression of peroxisome proliferator α(PPARα)and liver X receptor α(LXRα).The results showed that: compared with the negative control group,the weight gain rate,fat coefficient,Wat,TG content,MIP-1α and IL-8 expression,MCP-1 content,TNF-α expression and ALP activity of the model group were significantly increased(P<0.01);compared with the model group,the weight gain rate,MIP-1 α,IL-10 and IL-8 expression,Wat,FFA,TG content of the high-dose cholic acid group were significantly decreased(P<0.05)The activity of ALP,the content of FFA and the expression of IL-10 in the middle and low dose groups were significantly decreased(P<0.05),the expression of MIP-1α and IL-8 were significantly decreased(P<0.01),the weight gain rate and the expression of TNF-α in the middle dose group were significantly decreased(P<0.05).PPARα and LXRαreceptors were distributed in the nuclei of liver.The expression of PPAR α in model group was significantly lower than that in negative control group(P<0.01).The expression of PPAR α in high and medium dose cholic acid groups was significantly higher than that in model group(P<0.01),and that in low dose cholic acid groups was significantly higher than that in model group(P<0.05).The expression of LXRα in high,medium and low dose cholic acid groups was significantly lower than that in model group(P<0.01).At 120 min after oral administration of glucose,the blood glucose level in the model group was significantly higher than that in the negative control group(P<0.05),but significantly lower than that in the high,medium and low dose groups of cholic acid(P<0.01).At 120 minutes after intraperitoneal injection of insulin,the blood glucose in the model group was significantly higher than that in the negative control group(P<0.05),and the high-dose cholic acid group was significantly lower than that in the negative control group(P<0.05).These results indicate that cholic acid can regulate glucose and lipid metabolism by reducing lipid,inhibiting weight gain and improving insulin sensitivity in rats with metabolic inflammation;cholic acid can inhibit the formation of fat by up regulating the expression of PPARα and down regulating the expression of LXRα,so as to reduce the inflammatory response in rats with metaflammation. |
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