Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
World J Gastroenterol. 2012 Sep 21;18(35):4875-84. doi: 10.3748/wjg.v18.i35.4875.
To investigate the effect of Tangweian Jianji (TWAJJ) on the biomechanical and morphometrical remodeling of the upper gastrointestinal tract in diabetic rats.
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.
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 μg/L, 2.66 ± 0.44 μg/L, 2.03 ± 0.29 μg/L and 4.17 ± 0.54 μg/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 ± 0.07 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 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).
TWAJJ (high dose) treatment partly restored the morphometric and biomechanical remodeling of the upper gastrointestinal tract in diabetic rats.
观察糖痿煎剂对糖尿病大鼠上消化道组织形态和生物力学重塑的影响。
采用链脲佐菌素(40 mg/kg 体重)诱导 27 只大鼠糖尿病模型,将其随机分为糖尿病对照组(DM)、高剂量组(10 g/kg,T1 组)和低剂量组(5 g/kg,T2 组),每组 9 只,另设 10 只正常大鼠为正常对照组(Control)。TWAJJ 经口灌胃给药,每日 1 次。检测血糖和血清胰岛素水平,测量食管、十二指肠、空肠和回肠环段的周长、壁厚和开口角度,根据形态计量学数据计算残余应变。对食管和空肠段进行逐步扩张,获得长度、直径和压力变化数据,计算周向和纵向应力量。采用实时逆转录聚合酶链反应检测空肠组织中晚期糖基化终产物受体(RAGE)mRNA 水平。
实验结束时,DM、T1 和 T2 组大鼠的血糖水平明显高于对照组,而血清胰岛素水平明显低于对照组(血糖:30.23±0.41 mmol/L、27.48±0.27 mmol/L 和 27.84±0.29 mmol/L 比 5.05±0.04 mmol/L,P=1.65×10(-16)、P=5.89×10(-19) 和 P=1.63×10(-18);胰岛素:1.47±0.32 μg/L、2.66±0.44 μg/L、2.03±0.29 μg/L 和 4.17±0.54 μg/L,P=0.0001、P=0.029 和 P=0.025),但 DM、T1 和 T2 组之间无显著差异。DM 组大鼠食管和肠道各段的湿重/单位长度、壁厚和开口角度明显高于对照组(P 值分别为 0.009 至 0.004)。T1 组大鼠上述参数明显低于 DM 组(湿重,十二指肠:0.147±0.003 g/cm 比 0.158±0.001 g/cm,P=0.047;空肠:0.127±0.003 g/cm 比 0.151±0.002 g/cm,P=0.017;回肠:0.127±0.004 g/cm 比 0.139±0.003 g/cm,P=0.046;壁厚,食管:0.84±0.03 mm 比 0.94±0.02 mm,P=0.014;十二指肠:1.27±0.06 mm 比 1.39±0.05 mm,P=0.031;空肠:1.19±0.07 mm 比 1.34±0.04 mm,P=0.047;回肠:1.09±0.04 mm 比 1.15±0.03 mm,P=0.049;开口角度,食管:112.2±13.2˚比 134.7±14.7˚,P=0.027;十二指肠:105.9±12.3˚比 123.1±13.1˚,P=0.046;空肠:90.1±15.4˚比 115.5±13.3˚,P=0.044;回肠:112.9±13.4˚比 136.1±17.1˚,P=0.035)。在食管和空肠段,DM 组大鼠的内残余应变明显减小,外残余应变明显增大(P=0.022 和 P=0.035)。T1 治疗显著恢复了这种生物力学改变(P=0.011 和 P=0.019),但 T2 治疗没有。此外,DM 组大鼠食管和空肠壁的周向和纵向刚度均高于对照组。与 DM 组相比,T1 但不是 T2 治疗显著降低了空肠段的周向壁刚度(P=0.012)和食管段的纵向壁刚度(P=0.023)。T1 组大鼠空肠组织中 RAGE mRNA 水平明显低于 DM 组(P=0.0069)。
高剂量 TWAJJ 治疗部分恢复了糖尿病大鼠上消化道的形态和生物力学重塑。