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.

糖胃安对四氧嘧啶糖尿病胃轻瘫模型大鼠5-羟色胺2A受体的影响

目的:观察糖胃安对四氧嘧啶糖尿病胃轻瘫模型大鼠5-羟色胺2A(5-HT2A)受体的影响并探讨其作用机制。方法:以四氧嘧啶加200%熟地黄浓煎液造成四氧嘧啶糖尿病胃轻瘫模型大鼠,将40只该模型大鼠随机分为4组:糖胃安高剂量组在用格列齐特片20mg·kg-1的基础上,给予糖胃安31.75g·kg-1灌胃;糖胃安低剂量组在用格列齐特片20mg·kg-1的基础上,给予糖胃安15.88g·kg-1灌胃;阳性对照药吗叮啉组在用格列齐特20mg·kg-1的基础上,联合吗丁啉3.75mg·kg-1配合灌胃;模型对照组给予等量蒸馏水。另取10只正常大鼠作为正常对照组。本实验采用免疫组化方法观察中药糖胃安对该模型大鼠受体的影响。结果:糖胃安不仅能降低糖尿病胃轻瘫模型大鼠血糖,还可以明显改善大鼠胃肠5-羟色胺2A受体水平。与用药前相比,有显著性差异(P<0.01),与对照组相比,也有显著性差异(P<0.05)。结论:5-HT2A受体含量的增高是糖尿病胃轻瘫的重要原因之一,糖胃安能够明显改善5-HT2A受体水平,有显著的降低血糖、改善患者症状的作用。

糖胃安对胃轻瘫大鼠胃功能的影响

目的观察糖胃安对四氧嘧啶致糖尿病胃轻瘫模型大鼠对胃功能的影响。方法以四氧嘧啶加200%熟地浓煎液造成四氧嘧啶糖尿病胃轻瘫模型大鼠,连续给与糖胃安2周,观察糖胃安对大鼠血糖及血浆胃动素(MTL)、胰高血糖素(PG)、生长抑素(SS)的影响。结果糖胃安可降低MTL、PG、SS水平,与用药前相比,有显著性差异(P<0.01);与对照组相比,也有显著性差异(P<0.05)。结论糖胃安降低胃动素、胰高血糖素、生长抑素,并对降血糖有一定影响。

糖胃安煎剂改善糖尿病大鼠空肠生物力学重构的机制研究

目的:通过检测糖尿病大鼠脑源性神经营养因子(BDNF)及Trk受体Trk A、Trk B的表达变化与生物力学重构相关性,结合BDNF引起肠壁平滑肌形态及功能重构;肠壁平滑肌收缩张力改变影响生物力学重构的前期研究,探讨糖胃安的作用机制。方法:SD雄性大鼠30只,分为对照组、糖尿病模型组(链脲佐菌素40mg/kg)和糖胃安治疗组(链脲佐菌素40mg/kg造模+糖复安10g/kg灌胃60d)。免疫组化染色检测BDNF、Trk A和Trk B在空肠各层表达,通过图像、线性回归分析上述指标与生物力学重构的相关性。结果:糖尿病组与对照组比较,BDNF、Trk A和Trk B表达均显著降低(P<0.05,P<0.01);糖胃安能显著提高其表达(P<0.05,P<0.01);生物力学重构与上述指标表达呈负相关。结论:糖胃安通过提高BDNF、Trk A和Trk B表达,影响生物力学重构改善。

糖胃安煎剂对糖尿病胃肠病变大鼠Cajal间质细胞和P物质的影响

目的：研究糖胃安煎剂对糖尿病胃肠病变大鼠胃排空的影响,并探讨其作用机制。方法：2~3月龄Wistar雄性大鼠50只,10只大鼠作为正常组,另外40只腹腔注射50 mg·kg-1链脲佐菌素（STZ）复制1型糖尿病动物模型,尾静脉随机血糖≥16.9 mmol·L-1者为糖尿病大鼠模型建立,随机分为糖尿病模型组,糖胃安煎剂高、中、低剂量（15,10,5 g·kg-1）组,每组10只,正常组和糖尿病模型组给予等量蒸馏水灌胃。8周后取材,采用放射性核素单光子发射断层显像技术（SPECT）测定胃排空,免疫组织化学技术观察胃肌间层Cajal间质细胞变化,蛋白质免疫印迹法（Western blot）检测下丘脑P物质蛋白表达。结果：与正常组比较,糖尿病模型组大鼠的胃排空显著降低,胃肌间层阳性Cajal间质细胞显著降低,下丘脑P物质蛋白表达降低（P〈0.01）。与糖尿病模型组比较,糖胃安煎剂高、中剂量组的胃排空率升高,Cajal间质细胞升高,下丘脑P物质蛋白表达均升高（P〈0.05,P〈0.01）;糖胃安煎剂低剂量组的胃排空率,Cajal间质细胞,下丘脑P物质蛋白表达有升高趋势,但无统计学意义。结论：糖尿病胃肠病变大鼠胃排空降低,胃肌间层Cajal间质细胞减少,下丘脑P物质表达降低,糖胃安煎剂可能通过增加大鼠胃肌间层Cajal间质细胞,提高下丘脑P物质水平,促进糖尿病胃肠病变大鼠胃排空,改善胃肠动力和功能。