Mechanism Of Huayu Wendan Decoction On Islet Function And Pancreatic Fat Infiltration In IGT Rats Based On JNK/FoxO1 Signaling Pathway

Objective:To observe the effect of Huayu Wendan Decoction on the metabolism of glycolipid,inflammation and pancreatic fat infiltration in rats with IGT model,and further explore the mechanism of Huayu Wendan Decoction on the islet function and pancreatic fat infiltration of IGT rats from jnk/foxo1 signal pathway,and provide scientific support for the clinical application of the method of separation and elimination of discharge.Methods:In 70 SPF male SD rats,10 of them were randomly selected as blank group,and the rest were fed with high-fat and high sugar diet for 20 weeks to prepare IGT rat model.Thirty IGT rats were randomly divided into model group,Huayu Wendan Decoction group and metformin group,with 10 rats in each group;The Huayu Wendan Decoction group was given Huayu Wendan Decoction by gavage,the metformin group was given metformin hydrochloride suspension by gavage,and the blank group and model group were given normal saline by gavage for a total of 4 weeks.At the 25 th week,FPG and 2PG of rats were measured.Serum and pancreatic tissue samples were collected.The levels of fins,FFA,LEP,IL-6,TNF-? in serum and TG in pancreatic tissue were detected by ELISA.HOMA-IR and IAI were calculated.Histopathological changes and fat deposition of pancreas were observed by HE and oil red O staining.The mRNA expression levels of JNK,IRS-1,Akt and FoxO1 were detected by real time q PCR,and the protein and p Hosp Horylation levels of JNK,IRS-1,Akt and FoxO1 were detected by Western blot.Result:1.Analysis of body weight,FPG and 2PG : Before the intervention,compared with the blank group,the other three groups were significantly increased(P<0.01);at the 25 th week,compared with the blank group,the body weight,FPG,2PG of the remaining three groups were increased(P<0.01),compared with the model group,the body weight,FPG,2PG of the Huayu Wendan Decoction group and metformin group were decreased(P<0.05,P<0.01).2.Results analysis of serum fins content and calculation results of HOMA-IR and IAI:Compared with the blank group,fins and HOMA-IR of the other three groups were significantly increased,while IAI was decreased,with significant difference(P<0.05,P<0.01);compared with the model group,fins and HOMA-IR of Huayu Wendan Decoction group and metformin group were decreased,while IAI was increased(P<0.05,P<0.01).3.Results analysis of adipocytokines : Compared with the blank group,FFA and LEP of the other three groups were significantly increased(P<0.01);compared with the model group,FFA and LEP of Huayu Wendan Decoction group and metformin group were significantly decreased(P<0.05,P<0.01).4.Results analysis of inflammatory factors : Compared with the blank group,FFA and LEP of the other three groups were significantly increased(P<0.01);compared with the model group,FFA and LEP of Huayu Wendan Decoction group and metformin group were significantly decreased(P<0.05,P<0.01).5.TG content and pathological changes of pancreas:Compared with the blank group,TG of the other three groups increased significantly(P<0.01);compared with the model group,Tg of Huayu Wendan Decoction group and metformin group decreased(P<0.05,P<0.01).HE staining of pancreatic tissue:in the blank group,the pancreatic tissue structure was intact without steatosis or inflammatory infiltration.In the model group,the structure of islets was irregular,the volume of glandular cells became larger and the number decreased,a large number of fat vacuoles appeared in the glandular cells,the interlobular space became wider,and obvious fat infiltration was seen in the interstitium;in the Huayu Wendan Decoction group and metformin group,the structure of islets and glandular cells was complete,compared with the model group,the fat infiltration decreased,and the interlobular fat vacuoles became smaller.Oil red O staining of pancreatic tissue: the area of lipid droplets in each group was calculated.Compared with the blank group,the area of fat infiltration in the model group was significantly increased(P<0.01),and the degree was serious.The area of fat infiltration in the Huayu Wendan Decoction and metformin groups was decreased(P<0.01),and the degree was alleviated.6.Results analysis of real time PCR:There was no significant difference in Akt between two groups(P>0.05).Compared with the blank group,JNK and FoxO1 in the model group were significantly increased,while IRS1 was significantly decreased(P<0.05,P<0.01);compared with the model group,JNK and FoxO1 in the Huayu Wendan Decoction group and metformin group were decreased,while IRS1 was increased(P<0.05,P<0.01),but there was no significant difference in TG between the metformin group and Huayu Wendan Decoction group(P>0.05).7.Results analysis of Western blot :Compared with the blank group,JNK,FoxO1 and p-irs1ser307 in the model group were significantly higher Compared with the model group,Huayu Wendan Decoction and metformin could significantly increase the expression of IRS-1,p-Akt and p-foxo1,and reduce the high expression of JNK,FoxO1 and p-irs1ser307(P<0.05,P<0.01).There was no significant difference in Akt among the groups.Conclusion1.IGT model rats induced by long-term high-fat and high sugar diet were accompanied by pancreatic fat infiltration.2.Huayu Wendan Decoction can reverse the disorder of glucose and lipid metabolism in IGT rats and reduce the inflammatory reaction.3.Huayu Wendan Decoction can reduce fat deposition,improve islet function and reduce pancreatic self resistance in IGT model rats.4.Huayu Wendan Decoction may regulate the JNK / FoxO1 signaling pathway,inhibit the expression and p Hosp Horylation of JNK,enhance the p Hosp Horylation of p-foxo1 and improve the pancreatic fat infiltration in IGT rats,which may be one of the potential mechanisms of Huayu Wendan Decoction in improving IGT rats.