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Chinese Medicine Yitangkang Activates FXR Receptor And Down-regulates The Expression Of PEPCK And G6Pase On The Effect Of Liver Gluconeogenesis In T2DM Rats

Posted on:2021-04-04Degree:MasterType:Thesis
Country:ChinaCandidate:J T LiuFull Text:PDF
GTID:2434330614957588Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Purposes:In this experiment,we observed the effect of yitangkang on the expression of farneside derivative X receptor(FXR),phosphoenolpyruvate carboxykinase(PEPCK)and glucose-6-phosphatase(G6Pase)in type 2 diabetic rats,and explored the effect and mechanism of yitangkang on hepatogluconeogenesis in type 2 diabetic rats.Material and methods:Of the 70 SPF Wistar rats,10 were randomly selected as the normal control group,and the remaining 60 were induced by high-fat diets.The type 2 diabetes animal model was replicated by intraperitoneal injection of streptozotocin(STZ),and randomized Different interventions were given to the three groups.Rats in the Yitangkang group were given Yitangkang 10ml·kg-1 intragastrically + saline 2ml·kg-1 intraperitoneally,and the CDCA group were given 10 ml · kg-1 saline + intragastrically + CDCA preparation solution was injected intraperitoneally at 2ml· kg-1,blank control group and model control group were given intragastric injection of the same volume of normal saline + intraperitoneal injection of the same volume of normal saline,once a day for six consecutive weeks.On the weekends of 2,4,and 6,the fasting blood glucose and body weight of the rats were measured,and samples were taken on the 6th weekend.The changes in blood lipid levels of the rats in each group were detected with an automatic biochemical analyzer;the insulin levels of the rats in each group were measured by the Elisa method;Tissue sections were stained with HE staining and oil red O staining to observe the pathological morphological changes and lipid deposition of liver tissue;Western-ern Blot and RT-PCR techniques were used to detect FXR,PEPCK,G6 Pase protein and gene expression in rat liver tissue.Results:1.The rats in the blank control group were in good mental state,their water and stoolwere normal,and their skin color was smooth and smooth;after injection of stz,the weight of rats in the model group began to decrease significantly,the amount ofdrinking water increased sharply,and the amount of urine was also significantly increased.,Slow action,decreased feeding.Two weeks after the intervention of Yitangkang group and cdca group,the mental state of the two groups of rats began to improve significantly compared to the model group,the weight loss was slower,the eating situation increased,and the drinking and urination The amount has improved.2.The results of weight monitoring showed that before intervention,compared with the blank control group,the weight of the remaining three groups of rats increased significantly(P<0.01);after 6 weeks of intervention,compared with the blank control group,the remaining three groups were significantly larger.The weight of rats was significantly reduced(P<0.01);compared with the model control group,the weight of rats in the Yitangkang group and the cdca group significantly slowed down after intervention,and increased significantly compared with the model group (P<0.05).3.The FBG monitoring results showed that compared with the blank control group,the fbg of the remaining three groups of rats was significantly increased before the intervention(P<0.01),and there was no significant difference between the three groups(P> 0.05).After 4 and 6 weeks,compared with the blank control group,the fbg of the remaining three groups of rats was still significantly increased(P<0.01),compared with the model control group,the FBG of the rats in the Yitangkang group and the CDCA group was significantly reduced.(P<0.01).4.The results of blood lipid and insulin levels showed that compared with the blank control group,the serum of the remaining three groups of rats.The levels of ALTand AST were significantly increased(P<0.01);compared with the model control group,the ALT and AST of the Yitangkang group and the CDCA group were significantly reduced(P<0.05);There was no significant difference in ALT and AST between Yitangkang group and CDCA group(P > 0.05).5.The results of liver function test showed that compared with the blank control group,the levels of serum ALT and AST in the remaining three groups were significantly increased(P<0.01);compared with the model control group,the alt and CDCA group had ALT and AST were significantly reduced(P <0.05);compared with the cdca group,there was no statistical difference in alt and ast in the Yitangkang group (P> 0.05).6.HE staining results showed that the liver tissue of the blank control group was normal in morphology,the cells were arranged neatly,and the hepatic lobules were clear.No significant signs of steatosis and inflammation were seen;the model control group showed that the liver tissues of the rats were significantly different in size.And there are more fat vacuoles,the structural integrity of the liver tissue is damaged,the hepatic lobules lose the cord-like arrangement,and the performance of inflammatory cell infiltration can be seen;compared with the model group,the liver tissue fat of the Yitangkang group and the cdca group The degree of degeneration was significantly improved,the fat vacuoles were significantly reduced,the liver tissue structure was more complete,and no obvious inflammation and infiltration were seen.7.Oil red O staining results suggest that: the blank control group has normal liver staining expression and no significant lipid deposition;while the model control group has oil red o positive staining results and significant lipid deposition; compared with the model group In comparison,the oil red o positive staining results of the Yitangkang group and the cdca group were significantly reduced,the lipid deposition was significantly improved,and the improvement effect of the cdca group was more obvious.8.The results of Western blot showed that compared with the blank control group,the expression of FXR protein in the liver of the model control group was decreased(P<0.05),and the expression of PEPCK and G6 Pase protein was increased(P<0.05).In comparison,the expression of FXR protein in liver tissues of the Yitangkang group and the CDCA group was significantly increased(P<0.01),and the expression of PEPCK and G6 Pase protein was decreased(P<0.05).9.The results of immunohistochemistry showed that compared with the blank control group,the positive staining of PEPCK and G6 Pase proteins in the liver tissue of the model control group rats was significantly increased;compared with the model group,the liver tissues of the Yitangkang group and the CDCA group rats The positive staining of PEPCK and G6 Pase proteins was significantly decreased,and the FXR protein was significantly increased.Compared with the Yitangkang group,the positive staining of FXR protein was more significant in the CDCA group.The above protein expression results were consistent.10.RT-PCR test results showed that compared with the blank control group,the m RNA expression of FXR in the model group decreased(P<0.05),and the m RNA expression of PEPCK and G6 Pase increased significantly(P<0.01);compared with the model group,the benefit of The m RNA expression of FXR in Yitangkang group and CDCA group increased significantly,and the m RNA of PEPCK and G6Pase decreased significantly(P<0.01).Conclusion:1.The traditional Chinese medicine compound Yitangkang can improve glucose and lipid metabolism disorders and liver injury in type 2 diabetic rats.2.Chinese traditional medicine Yitangkang can regulate liver gluconeogenesis in type2 diabetic rats3.The traditional Chinese medicine compound Yitangkang can activate the expression of FXR.4.The effect of traditional Chinese medicine Yitangkang on blood glucose regulation in type 2 diabetic rats can be achieved by activating the nuclear receptor FXR to down-regulate the expression of PEPCK and G6 Pase,thereby affecting liver gluconeogenesis.
Keywords/Search Tags:Chinese herbal compound of Yitangkang, Type 2 diabetes, FXR, Glycoside
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