Angptl3在胃转流术治疗2型糖尿病大鼠中作用的相关研究

Research of Angptl3 in gastric bypass for the treatment of type 2 diabetes mellitus in rats

目的 观察Roux-en-Y 胃转流术对链脲佐菌素造模的糖尿病大鼠血糖控制效果及各组大鼠血清Angptl3 在不同阶段水平的变化,探讨Angptl3 与2 型糖尿病的关系以及Roux-en-Y 胃转流术对其影响.方法 分别取链脲佐菌素造模成功的T2DM 健康雄性大鼠及周龄相当的非造模健康雄性大鼠各20 只.将其随即分为T2DM 手术组（DRO 组）、T2DM 假手术组（DSO 组）、正常手术组（NRO 组）、正常假手术组（NSO组）,每组各10 只.分别检测各组大鼠手术前、手术后第1 周、手术后第4 周 及手术后第8 周体重、空腹血糖、血清胰岛素及血清Angptl3 水平,观测其变化,并分析其相关性.结果 术前,DRO 组与DSO 组及NRO 组与NSO 组组间比较,各组组内大鼠的体重、FPG 、INS、血清Angptl3水平差异均无统计学意义（P〉0.05）;在DRO 组及DSO 组中FPG 、INS 、血清Angptl3 水平均明显高于NRO 组（P〈0.01）与NSO 组（P〈0.01）.术后第1 周,DRO 组体重、 FPG 、INS 、血清Angptl3 水平较术前均有所下降,除体重（P〉0.05）外,其余指标与术前相比均有显著性差异（P〈0.05）;术后第 4 周,DRO 组体重、 FPG 、INS 、血清Angptl3 水平较术前及术后第1 周均有所下降,除体重（P〉0.05）外,其余指标与术前相比均有显著性差异（P〈0.05）;术后第8 周,DRO 组上诉各项指标水平在大鼠血清中的水平进一步下降,除体重（P〉0.05）外,其余指标与术前相比均有显著性差异（P〈0.01）.除DRO 组外其余三组组间,术前、术后第1 周、术后第4 周及术后第8 周,体重、FPG 、INS 及血清Angptl3 水平进行比较,差异均无统计学意义（P〉0.05）.在手术前、手术后第1 周、手术后4 周及术后第8 周中,血清Angptl3 水平与其对应的血清 INS 水平在DRO 组与DSO 组中均呈正相关（P〈0.01）,其相关系数分别为r=0.858,r=0.422.结论 Roux-en-Y 胃转流术能有效降低T2DM 大鼠血糖,胃转流术控制血糖可能部分是通过降低Angptl3 的分泌进而降低胰岛素抵抗,Roux-en-Y 胃转流术对正常大鼠血糖无影响.

Objective To observe the effect and the possible role of Roux-en-Y gastric bypass on blood glucose of streptozotocin diabeticrats and level of serum Angptl3 of rats in different phases.To explore the relationship between Angptl3 and type 2 diabetes . Methods Thetwenty healthy male rats were selected and twenty SD male rats with T2DM were selected at the same time .Then they were randomly divided into 4 groups T2DM-Roux-en-Y Gastric Bypass group（DRO group）,T2DM-sham operation group（DSO group）,operation group（NRO group） and normal-sham operationgroup（NSO group）,10 rats in each group . Detect the following medical Indexes： their weight, plasma glucose（FPG） level, serum insulin （INS） level andChemerin level, which were determined by ELISA before operation and on week 4,8 after operation,respectively. To observe the change of these indicators andto analyze the correlation between them. Results Before operation, DRO group compared with DSO group and NRO group compared with NSO group thatthe weight, FPG level,INS level and Chemerin leve were not statistically significant （P 〉 0.05）; however,FPG level, INS level and Chemerin level in both DROgroup and DSO group were significantly higher than those in NRO group respectively （P〈0.01）; it had the same result that NSO group compared with DROgroup and DSOgroup （P〈0.01）.On first weeks after operation, FPG, INS, body weight, serum level of Angptl3 were decreased, other indexes compared withthose before operation were significantly different （P 〈 0.05） ,in addition to body weight （P 〉 0.05）,in DRO group. On fourth weeks after operation,FPG, INS, body weight, serum Angptl3 level was decreased than first weeks after operation, other indexes compared with those before operation weresignificantly different （P 〈 0.05）, in addition tobody weight （P 〉 0.05）,in DRO group. On eighth weeks after operation, level of appeal indices to furtherdecline in serum of rats, other indexes compared with those before operation were significantly different （P 〈 0.01）, in addition to body weight （P 〉 0.05）, inDRO group. The weight, FPG, INS and Angptl3 level in serum, were not statistically significant （P 〉 0.05） on preoperative, first weeks after operation, fourthweeks after operation and eighth weeks after operation , in the other three groups except in the DRO group. The level of serum INS and serum Angptl3 in thecorresponding were positively correlated in the DRO group and DSO group （P 〈 0.01）,on preoperative, first week after operation, operation aftereighth weeks and 4 weeks after operation. The correlation coefficients were respectively r=0.858, r=0.422. Conclusions Roux-en-Y gastric bypass surgery caneffectively reduce the blood glucose in T2DM rats, it may be partly by reducing the secretion of Angptl3 that gastric bypass control blood glucose and reduceinsulin resistance. Roux-en-Y gastric bypass surgery does not have effect on normal rats.