| ObjectiveTo study the effect of duodenal-jejunal bypass(DJB)on liver bile acid metabolism in rats with type 2 diabetes(T2DM)and the possible mechanism of hypoglycemic effect.Methods1.Induce healthy male SD rats through high-fat diet and low-dose streptozotocin to establish type 2 diabetes(T2DM)model rats.Randomly divided into duodenal amputation orthotopic anastomosis(sham operation group,namely Sham group)and duodenal jejunum bypass operation group(surgery group,namely DJB group).The fasting body weight,fasting blood glucose and 2h postprandial blood glucose of the rats were measured before operation and 1,2,3 weeks after operation;respectively,before and after the 4th week after operation,the blood of the canthus canthus was collected to detect insulin and fasting state.Cholesterol and triglyceride levels,and calculate the level of rat insulin resistance index;the total bile acid concentration in the bile of the common bile duct,hepatic portal vein blood,and feces of the rats after the meal was measured at 4 weeks after surgery.2.Animals were sacrificed at 4 weeks after surgery to take liver samples,and the farnesyl derivative X receptor(FXR)and small heterodimeric chaperone(SHP)in liver tissue were detected by reverse transcription PCR(RT-PCR)and Western blot respectively,Glucose-6-phosphatase(G6Pase),phosphoenolpyruvate carboxykinase(PEPCK),sterol regulatory element binding protein 1c(SREBP-1c),peroxisome proliferator-activated receptor-α(PPAR-α)m RNA and protein expression levels.Results1.There was no significant difference in fasting weight between Sham group and DJB group before operation.One week after operation,rats in the DJB group and the Sham group showed significant weight loss,and there was no statistically significant difference between the groups(P > 0.05).However,the fasting body weight(317.67 ± 22.74,326.08 ± 39.17)of the DJB group was lower than that of the Sham group(355.17 ± 32.88,376.25 ± 29.90)at 2 and 3 weeks after the operation(P <0.05).2.There was no significant difference in fasting blood glucose,fasting blood glucose 2h after meal,fasting serum insulin and insulin resistance index level in Sham group and DJB group before operation.At 1,2,and 3 weeks after the operation,the blood glucose(8.37 ± 1.51,8.02± 1.45,9.32 ± 2.71)in the DJB group after meal was lower than that in the Sham group(19.70±3.00,19.23±2.11,21.08±5.55),The difference was statistically significant(P <0.01).Postoperative fasting serum insulin(32.73±3.95)in the DJB group was lower than that in the Sham group(42.08±2.99),the difference was statistically significant(P <0.01),while the postoperative insulin resistance index(8.02±1.25)in the DJB group was In the Sham group(10.97 ± 1.11),the difference was statistically significant(P<0.01).3.There was no significant difference in serum cholesterol and triglyceride levels in Sham group and DJB group before operation,while serum cholesterol level in DJB group(1.70±0.26)was lower than Sham group(2.14±0.32)after operation,the difference was statistically significant Significance(P <0.05).There was no significant difference in serum triglyceride levels(0.53±0.15)between DJB group and Sham group(0.50±0.20)after operation(P > 0.05).Postoperative DJB group serum triglyceride(0.53±0.15)decreased compared with preoperative(0.69± 0.20),but the difference was not statistically significant(P > 0.05).4.The total bile acid concentration in the common bile duct bile,hepatic portal vein blood and feces in postoperative DJB group rats(31.07±10.40,219.27±91.65,2.13±0.52)was higher than that in Sham group(19.91±4.56,111.07±32.20,1.36±0.34),the difference was statistically significant(P <0.05).5.The FXR(1.66 ± 0.45,1.28 ± 0.15),SHP(1.35 ± 0.19,1.20 ± 0.12),PEPCK(2.76±1.67,1.6±0.25),G6Pase(3.34±2.11,1.38±0.25),PPAR-α(2.54± 0.81,1.65 ± 0.47)in the liver tissue of the DJB group postoperatively were higher in m RNA and protein levels than the Sham group(P <0.05);SREBP-1c(0.55 ± 0.29,0.48 ± 0.19)was lower in m RNA and protein water than in Sham group(P <0.05).Conclusion1.DJB surgery may upregulate the bile acid synthesis in the liver,and increase the total bile acid concentration in the enterohepatic circulation.2.DJB may play a role in reducing blood sugar by affecting the bile acid-FXR-SHP pathway,inhibiting fat synthesis and enhancing lipolysis,thereby reducing rat insulin resistance and improving its insulin sensitivity. |
