Effect of Tangweian Jianji on upper gastrointestinal remodeling in streptozotocin-induced diabetic rats

AIM： To investigate the effect of Tangweian Jianji （TWAJJ） on the biomechanical and morphometrical remodeling of the upper gastrointestinal tract in diabetic rats. METHODS： Diabetes was induced in 27 rats by in- jecting streptozotocin （40 mg/kg body weight）, the animals were then divided into three groups （n = 9 in each group）, i.e., diabetic control （DM）; high dose （10 g/kg, T1） and low dose （5 g/kg, T2）. Another 10 rats acted as normal controls （Control）. TWAJJ was admin- istered by gavage once daily. Blood glucose and serum insulin levels were measured. Circumferential length, wall thickness and opening angle were measured from esophageal, duodenal, jejunal and ileal ring segments. The residual strain was calculated from the morpho- metric data. Step-wise distension was carried out on esophageal and jejunal segments. The obtained data on the length, diameter and pressure changes were then used to calculate the circumferential and longitu- dinal stresses and strains. Real-time reverse transcrip- tion polymerase chain reaction was used to detect the receptor of advanced glycation end-products （RAGE） mRNA level in jejunal tissues. RESULTS： At the end of the experiment, the blood glucose level was significantly higher and the serum insulin level was significantly lower in DM, T1 and T2 groups than in the control group （Glucose： 30.23 ± 0.41 mmol/L, 27.48 ± 0.27 mmol/L and 27.84 ± 0.29 mmol/ L vs 5.05 ± 0.04 mmol/L, P = 1.65 x 10-16, P = 5.89 x 1019 and P = 1.63 x 10-Is, respectively; Insulin： 1.47 ± 0.32 °tg/L, 2.66 ± 0.44 pg/L, 2.03 ± 0.29 pg/L and 4.17 ± 0.54 pg/L, P = 0.0001, P = 0.029 and P = 0.025, re- spectively）. However, these levels did not differ among the DM, T1 and T2 groups. The wet weight per unit length, wall thickness and opening angle of esophageal and intestinal segments in the DM group were signifi- cantly higher than those in the control group （from P = 0.009 to P = 0.004）. These parameters in the T1 group were significantly lower than those in the DM group （wet weight, duodenum： 0.147 ± 0.003 g/cm vs 0.158 ± 0.001 g/cm, P = 0.047; jejunum, 0.127 ± 0.003 g/cm vs 0.151：1：0.002 g/cm, P = 0.017; ileum, 0.127 ± 0.004 g/cm vs 0.139 ± 0.003 g/cm, P = 0.046; wall thickness, esophagus： 0.84±0.03 mm vs 0.94 ± 0.02 ram, P = 0.014; duodenum： 1.27 ± 0.06 mm vs 1.39 ± 0.05 ram, P = 0.031; jejunum： 1.19 ± 0.07 mm vs 1.34 ± 0.04 mm, P = 0.047; ileum： 1.09 ± 0.04 mm vs 1.15 ± 0.03 mm, P = 0.049; opening angle, esophagus： 112.2 ± 13.2° vs 134.7 ± 14.7°, P = 0.027; duodenum： 105.9 ± 12.3° vs 123.1 ± 13.1°, P = 0.046; jejunum： 90.1 ± 15.4° vs 115.5 ± 13.3°, P = 0.044; ileum： 112.9 ± 13.4° vs 136.1 ± 17.1°, P = 0.035）. In the esophageal and jejunal segments, the inner residual stain was significantly smaller and the outer residual strain was larger in the DN group than in the control group （P = 0.022 and P = 0.035）. T1 treatment significantly restored this biomechanical alteration （P = 0.011 and P = 0.019）, but T2 treatment did not. Fur- thermore, the circumferential and longitudinal stiffness of the esophageal and jejunal wall increased in the DM group compared with those in the control group. T1, but not T2 treatment, significantly decreased the cir- cumferential wall stiffness in the jejunal segment （P = 0.012） and longitudinal wall stiffness in the esophageal segment （P = 0.023）. The mRNA level of RAGE was significantly decreased in the T1 group compared to that in the DN group （P = 0.0069）. CONCLUSION： TWAJJ （high dose） treatment partly restored the morphometric and biomechanical remodel- ing of the upper gastrointestinal tract in diabetic rats.

AIM:To investigate the effect of Tangweian Jianji(TWAJJ) on the biomechanical and morphometrical remodeling of the upper gastrointestinal tract in diabetic rats.METHODS:Diabetes was induced in 27 rats by injecting streptozotocin(40 mg/kg body weight),the animals were then divided into three groups(n = 9 in each group),i.e.,diabetic control(DM);high dose(10 g/kg,T1) and low dose(5 g/kg,T2).Another 10 rats acted as normal controls(Control).TWAJJ was administered by gavage once daily.Blood glucose and serum insulin levels were measured.Circumferential length,wall thickness and opening angle were measured from esophageal,duodenal,jejunal and ileal ring segments.The residual strain was calculated from the morphometric data.Step-wise distension was carried out on esophageal and jejunal segments.The obtained data on the length,diameter and pressure changes were then used to calculate the circumferential and longitudinal stresses and strains.Real-time reverse transcription polymerase chain reaction was used to detect the receptor of advanced glycation end-products(RAGE) mRNA level in jejunal tissues.RESULTS:At the end of the experiment,the blood glucose level was significantly higher and the serum insulin level was significantly lower in DM,T1 and T2 groups than in the control group(Glucose:30.23 ± 0.41 mmol/L,27.48 ± 0.27 mmol/L and 27.84 ± 0.29 mmol/L vs 5.05 ± 0.04 mmol/L,P = 1.65 × 10-16,P = 5.89 × 10-19 and P = 1.63 × 10-18,respectively;Insulin:1.47 ± 0.32 g/L,2.66 ± 0.44 g/L,2.03 ± 0.29 g/L and 4.17 ± 0.54 g/L,P = 0.0001,P = 0.029 and P = 0.025,respectively).However,these levels did not differ among the DM,T1 and T2 groups.The wet weight per unit length,wall thickness and opening angle of esophageal and intestinal segments in the DM group were significantly higher than those in the control group(from P = 0.009 to P = 0.004).These parameters in the T1 group were significantly lower than those in the DM group(wet weight,duodenum:0.147 ± 0.003 g/cm vs 0.158 ± 0.001 g/cm,P = 0.047;jejunum,0.127 ± 0.003 g/cm vs 0.151 ± 0.002 g/cm,P = 0.017;ileum,0.127 ± 0.004 g/cm vs 0.139 ± 0.003 g/cm,P = 0.046;wall thickness,esophagus:0.84 ± 0.03 mm vs 0.94 ± 0.02 mm,P = 0.014;duodenum:1.27 ± 0.06 mm vs 1.39 ± 0.05 mm,P = 0.031;jejunum:1.19 ± 0.07mm vs 1.34 ± 0.04 mm,P = 0.047;ileum:1.09 ± 0.04 mm vs 1.15 ± 0.03 mm,P = 0.049;opening angle,esophagus:112.2 ± 13.2 vs 134.7 ± 14.7,P = 0.027;duodenum:105.9 ± 12.3 vs 123.1 ± 13.1,P = 0.046;jejunum:90.1 ± 15.4 vs 115.5 ± 13.3,P = 0.044;ileum:112.9 ± 13.4 vs 136.1 ± 17.1,P = 0.035).In the esophageal and jejunal segments,the inner residual stain was significantly smaller and the outer residual strain was larger in the DM group than in the control group(P = 0.022 and P = 0.035).T1 treatment significantly restored this biomechanical alteration(P = 0.011 and P = 0.019),but T2 treatment did not.Furthermore,the circumferential and longitudinal stiffness of the esophageal and jejunal wall increased in the DM group compared with those in the control group.T1,but not T2 treatment,significantly decreased the circumferential wall stiffness in the jejunal segment(P = 0.012) and longitudinal wall stiffness in the esophageal segment(P = 0.023).The mRNA level of RAGE was significantly decreased in the T1 group compared to that in the DM group(P = 0.0069).CONCLUSION:TWAJJ(high dose) treatment partly restored the morphometric and biomechanical remodeling of the upper gastrointestinal tract in diabetic rats.