| Objective: To study the role of the bile acid pathway of Duodenal-Jejunal Bypass(DJB),New Biliopancreatic Diversion(NBPD),Duodenal-Jejunal Exclusion(DJE)in the effects of blood glucose and total bile acids in type 2 diabetic rat model during these process.Methods:1.Sixty diabetic rats were randomly divided into four groups.They were performed DJB surgery,NBPD surgery,DJE surgery and duodenal transection and in situ anastomosis(Sham,sham operation group).Weekly and postoperative 24 th week were measured fasting lipids and 2h postprandial blood glucose.Fasting total serum bile acids were measured at the 24 th week after surgery.Samples of liver and intestine were taken and total RNA and total protein were extracted.2.The mRNA expression of bile acid receptor(FXR)gene,cholesterol regulatory element binding protein(SREBP-1)gene and cholesterol 7?-hydroxylase(CYP7A1)gene were detected by RT-PCR and relative quantitative PCR.3.Detection of liver protein expression by Western-Blot.Results:1.Blood glucose(unit:mmol/L)2 hours postprandial at 1 week before surgery in all rats: DJB group(26.4±2.2),NBPD group(25.8±2.1),DJE group(26.4±2.2),false In the operation group(26.7±3.0),there was no significant difference among the groups(P>0.05);postprandial 2h postprandial blood glucose(unit: mmol/L): DJB group(16.3±4.0),NBPD group(20.6±3.3),DJE group(27.3±2.2),and sham operation group(26.9±3.6).DJB group and NBPD group had lower blood glucose levels than DJE group and sham group(P<0.05).There was no significant difference in blood glucose between DJE group and sham operation group.The blood glucose levels of DJB group and NBPD group were lower than that of 1 week before operation(P<0.05).2.Comparison of the relative expression of FXR mRNA in liver of all surgical methods: The expression of FXR in the DJB group(0.862±0.207)was not statistically different from the other three groups(P>0.05);the expression of FXR in the NBPD group(1.564 ± 0.031)higher than DJE group(0.434 ± 0.062),the difference was statistically significant(P <0.05),FXR expression level of NBPD group was no significant difference with sham operation group(1.000 ± 0.369)(P> 0.05)There was no significant difference in FXR expression between DJE group and sham group(P>0.05).3.Comparison of the expression of FXR mRNA in the intestinal tracts of various operations: There was no statistical difference in the expression of FXR mRNA in the DJB group(0.382±0.206),in the NBPD group(0.681±0.125),and in the sham operation group(1.000±0.338).Significance(P>0.05);There was no significant difference in the expression of FXR between NBPD group and the sham group(P>0.05);The expression of FXR in the DJE group(2.593±0.481)was higher than that of the DJB group,the NBPD group,and the sham operation group.The difference was statistically significant(P<0.05).4.The expression of FXR protein in liver of each operation: The expression of FXR protein in NBPD group(1.152±0.031)and DJB group(1.040±0.019)was higher than that in DJE group(0.731±0.087)and sham operation group(0.671 ± 0.040),the difference was statistically significant(P <0.05).5.The relative expression of SREBP-1c mRNA in the liver of each surgical model was compared: DJB group: 1.783±0.657;NBPD group: 2.429±0.677;DJE group: 1.477±0.768;sham group: 1.000±0.129.There was no significant difference in the expression of SREBP-1 mRNA among all groups(P>0.05).6.Fasting cholesterol level(unit: mmol/L)at 1 week before operation in all rats: DJB group(1.750±0.676),NBPD group(1.750±0.825),DJE group(1.717±0.115),sham operation group(1.708±0.113),there was no statistical difference between the groups(P>0.05);24 weeks after operation(unit: mmol/L): DJB group(1.892±0.679),NBPD group(1.963±0.329),DJE There was no significant difference between the two groups(2.059±0.277)and sham operation group(2.023±0.385)(P>0.05).There was no significant difference in cholesterol level between the 24 th week and 1st week after operation(P>0.05).0.05).7.Fasting triglyceride levels(mmol/L)at 1 week before surgery in all rats: DJB group(1.125±0.168),NBPD group(1.130±0.049),DJE group(1.168±0.152),sham operation Group(1.137±0.090),there was no statistical difference between the groups(P>0.05);24 weeks after operation(unit: mmol/L): DJB group(0.885±0.176),NBPD group(1.043±0.182)DJE group(1.319±0.154)and sham operation group(1.465±0.268),DJB group and NBPD group had lower levels of triglyceride than DJE group and sham group(P<0.05).At 24 weeks,the levels of triglyceride in DJB group and NBPD group were lower than 1 week before surgery(P<0.05).8.Comparison of the relative expression of CYP7A1 mRNA in livers of different surgical methods: There was no significant difference in the expression of CYP7A1 mRNA between the DJB group(0.395±0.259)and the other three groups(P>0.05);the expression amount in the NBPD group(1.426±0.159))Compared with DJE group(0.510±0.098),the difference was statistically significant(P<0.05).There was no significant difference between NBPD group expression and sham operation group(1.000±0.180)(P>0.05);DJE expression level There was no significant difference between the sham group and the sham group(P>0.05).9.Fasting total serum bile acid content(unit: ?mol/L)in each surgical group's rat: DJB group(78.32±26.51),NBPD group(50.45±18.75),DJE group(33.63±13.58),sham operation group(18.13±)5.51),there was no significant difference between groups(P>0.05).Conclusion: 1.Biliary and pancreatic bypass after DJB affect the liver bile acid receptor upregulation and intestinal bile acid receptor downregulation,improve liver lipotoxicity and then produce hypoglycemic effect,is one of the mechanism of intestinal bypass hypoglycemic.Intestinal exclusion may not be hypoglycemic.2.Changes in the bile acid pathway after bowel bypass do not improve hepatic lipotoxicity by regulating cholesterol levels. |
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