GK大鼠（改良）袖状胃切除术模型的建立及其降糖作用机制的研究

发布时间：2018-05-09 00:17

本文选题：改良 + 袖状胃切除术　；参考：《华中科技大学》2011年博士论文

【摘要】：目的：用GK大鼠建立袖状胃切除术手术模型,借助此模型来探讨袖状胃切除术(SG)对血糖的控制效果。方法：23只GK大鼠随机分为袖状胃切除组(SG)、假手术组(sham-SG)和饮食配对组(PF)。体重、进食量、空腹血糖、口服葡萄糖耐量试验(OGTT)、胰岛素耐量试验(ITT)和空腹胰岛素浓度在特定的时间内被检测。结果：SG手术模型的成功率为100%。自术后第4周起,SG和PF组与sham-SG组间的体重增量有着明显的统计学意义(P0.01)。SG组空腹血糖水平较sham-SG和PF组明显改善。SG组较PF组和sham-SG组明显改善对葡萄糖耐量的水平,手术后第2周葡萄糖耐量曲线下面积(AUC)较术前减少约28.1%(P0.01),较饮食配对组减少约21%(P0.01)。SG组大鼠术后胰岛素耐量和胰岛素抵抗指数(HOMA-IR)较sham-SG和PF组明显改善。结论：SG能够直接控制2型糖尿病而不是继发于体重减轻的效果。SG是一种相对稳定的降糖手术模型。目的：探讨袖状胃切除术的降糖作用及其机制。方法：随机将GK大鼠分为袖状胃切除(SG)组、假手术(sham-SG)组、饮食配对(PF)组和空白对照(Control)组。动态观察手术前和手术后24周中各组大鼠体重、空腹血糖、口服葡萄糖耐量试验(OGTT)、胰岛素耐量试验(ITT)、胰岛素、Ghrelin及GLP-1浓度的变化。结果：自术后第4周起,SG和PF组与sham-SG和Control组之间的体重增量有明显统计学意义(P0.01)。术后SG组空腹血糖浓度较其它3组明显降低(P0.05),SG组术后第2周OGTT曲线下面积(AUC)较其术前减少约28.1%(P0.01),相对于其它3组有显著性的差异(P0.05)。术后第6周的ITT显示SG组胰岛素敏感性较sham-SG组明显改善,血糖水平变化明显降低。实验期间,与sham-SG组相比,SG组胰岛素浓度无明显变化(P0.05), Ghrelin浓度明显下降(P0.01), GLP-1浓度上升(P0.01)。结论：SG降糖效果确切,能够独立于体重的变化而直接有效地降低血糖。术后Ghrelin浓度下降、GLP-1浓度升高可能是SG降糖的主要机制。目的：建立胃袖状切除附加改良空回肠旁路的GK大鼠模型并对其分析。方法：将27只GK大鼠随机分为改良胃袖状切术(MSG)组、假手术(sham-MSG)组、饮食配对组(PF)组和空白对照(Controls)组。动态观察手术前和手术后16周体重、空腹血糖、口服葡萄糖耐量试验(OGTT)、胰岛素浓度、胰岛素抵抗指数(HOMA-IR)及其体内血脂水平的变化。结果：从手术后第4周起MSG与sham-MSG和PF组的体重增量有明显统计学差异(P0.01)。MSG组空腹血糖浓度较其它3组明显降低。术后第2周MSG组的OGTT曲线下面积(AUC)较术前减少约38.9%(P0.01),而在sham-MSG和PF组却无以上明显变化。实验期间,MSG组胰岛素敏感性及其分泌量明显改善,而在sham-MSG组却无以上明显变化。与PF组和sham-MSG组相比,MSG组在术后的血脂浓度得到明显改善。这些结果显示后肠在血糖调节中可能起到了重要的作用。结论：MSG独立于体重和进食量的变化直接控制GK大鼠体内血糖水平,为2型糖尿病治疗机制的研究提供了一种稳定、持久的降糖手术模型。目的：研究改良袖状胃切除术的降糖作用,并对其降糖机制进行初步探讨。方法：54只GK大鼠和6只Wistar大鼠随机分为改良袖状胃切除(modified sleeve gastrectomy, MSG)组,延迟-改良袖状胃切除(delayed-modified sleeve gastrectomy,MSG)组,袖状胃切除(sleeve gastrectomy, SG)组,对应MSG组的假手术(sham-MSG)组,对应SG组的假手术(sham-SG)组,药物治疗(罗格列酮,rosiglitazone, RSG)组,限制饮食(food restriction, FR)组；空白对照(Controls)组;Wistar大鼠构建为(Wistar MSG, WMSG)组。动态观察手术前后16周中各组大鼠对应的检测项目：体重、空腹血糖、口服葡萄糖耐量试验(OGTT)、胰岛素耐量试验(ITT)；胰岛素、Ghrelin、GLP-1和GIP浓度的变化。在术后第16周,组织中insulin、Ghrelin、GLP-1和GIP(胰腺、末端回肠、十二指肠和下丘脑)对应基因表达的变化水平及其手术后胰腺和末端回肠等组织的形态学变化。结果：手术后,MSG组对葡萄糖耐量较其它各组的GK大鼠明显改善。术后第2周,MSG组行OGTT后的曲线下面积较术前减少38.9%(P0.001),较SG减少23.9%(P=0.007),而sham-MSG/SG、Controls和FR组都没有以上的变化发生。MSG组术后2周对葡萄糖耐量的改善程度较该组术前(SG术后8周)明显。MSG组行ITT后血糖水平变化较RSG改善明显。术后,MSG组空腹血浆Ghrelin水平较假手术组明显改善(P0.001),MSG组进食葡萄糖后血浆GLP-1水平较SG和假手术组明显升高(P0.001)。术后MSG组胰岛素水平较SG和假手术组明显改善(P0.05)。术后16周,MSG组织中的胰岛素和GLP-1基因的表达水平明显上升,并且MSG组胰岛形态明显改善,阳性B细胞量和胰岛内成熟腺泡的电子密度都明显增加,胰岛细胞水肿现象明显缓解。这些结果显示后肠在血糖调节中起到了重要的作用。结论：MSG是一种相对稳定的、独立与体重和进食量的变化外直接改善血糖并改善胰岛素敏感性的一种手术方式；MSG进一步证实了2型糖尿病的病因可能与体内多种激素分泌的失衡有关,重新调节体内胰岛素内分泌轴的平衡可能是治疗糖尿病的有效方法。
[Abstract]:Objective: to establish a model of sleeve gastrectomy in GK rats and to explore the effect of sleeve gastrectomy (SG) on the control of blood glucose. Methods: 23 GK rats were randomly divided into sleeve gastrectomy group (SG), sham operation group (sham-SG) and diet paired group (PF). Body weight, intake, fasting glucose, oral glucose tolerance test (OGTT), islets of pancreas, and islets of pancreas. The ITT and fasting insulin concentrations were detected in a specific time. Results: the success rate of the SG operation model was 100%. fourth weeks after the operation. The weight gain between the SG and PF group and the sham-SG group had significant statistical significance (P0.01) the fasting blood glucose level in the.SG group was significantly higher than that in the sham-SG and PF groups. The level of glucose tolerance was significantly improved. The area under the glucose tolerance curve (AUC) decreased by about 28.1% (P0.01) second weeks after the operation. Compared with the diet group, the insulin resistance and insulin resistance index (HOMA-IR) were significantly improved after operation in the group.SG group (P0.01). Conclusion: SG can directly control type 2 diabetes mellitus. Rather than secondary weight loss,.SG is a relatively stable glucose lowering surgery model.
Objective: To investigate the hypoglycemic effect and mechanism of sleeve gastrectomy. Methods: GK rats were randomly divided into sleeve gastrectomy (SG) group, sham operation (sham-SG) group, diet pairing (PF) group and blank control group (Control). The body weight, fasting glucose tolerance test (OGTT), pancreatic islet in each group were dynamically observed before and 24 weeks after operation. Changes in the concentration of insulin, Ghrelin and GLP-1. Results: the weight increment between the SG and PF groups and the sham-SG and Control groups from the fourth weeks after the operation was statistically significant (P0.01). The concentration of fasting blood glucose in the group SG group was significantly lower than that of the other 3 groups (P0.05), and the area under the OGTT curve in the SG group was less than that of the preoperative second weeks after the operation. About 28.1% (P0.01), compared with the other 3 groups (P0.05). The ITT of sixth weeks after operation showed that the insulin sensitivity of group SG was significantly improved and the level of blood glucose decreased obviously. During the experiment, there was no significant change in the concentration of insulin in the SG group (P0.05), the concentration of Ghrelin (P0.01), GLP-1 concentration increased (P) (P) (P) (P) (P) (P) increased (P). 0.01). Conclusion: SG hypoglycemic effect is accurate, can be independent of the changes in body weight and directly effectively reduce blood sugar. After the operation, the concentration of Ghrelin decreased, and the increase of GLP-1 concentration may be the main mechanism of SG hypoglycemic.
Objective: to establish a GK rat model with modified gastric sleeve excision with modified empty ileum bypass. Methods: 27 GK rats were randomly divided into modified gastric sleeve resection (MSG) group, sham operation (sham-MSG) group, diet paired group (PF) group and blank control group (Controls). The body weight, fasting glucose and oral Portuguese were observed before and after the operation. Changes in glucose tolerance test (OGTT), insulin concentration, insulin resistance index (HOMA-IR) and blood lipid levels in the body. Results: there was significant difference in weight increment between MSG and sham-MSG and PF groups from fourth weeks after the operation (P0.01) the concentration of fasting blood glucose in the.MSG group was significantly lower than that in the other 3 groups. The area under the OGTT curve of the MSG group at second weeks after the operation (AU) C) decreased by about 38.9% (P0.01) compared with preoperative, but there was no obvious change in the sham-MSG and PF groups. During the experiment, the insulin sensitivity and secretion of the MSG group improved obviously, but there was no obvious change in the sham-MSG group. Compared with the PF group and the sham-MSG group, the blood lipid concentration in the group MSG was significantly improved. These results showed that the posterior intestine was in the blood sugar. It may play an important role in the regulation. Conclusion: MSG independent of the change of weight and food intake directly controls the blood glucose level in GK rats, and provides a stable and lasting model of hypoglycemic operation for the study of the mechanism of type 2 diabetes.
Objective: To study the hypoglycemic effect of modified sleeve gastrectomy and to explore its hypoglycemic mechanism.
Methods: 54 GK rats and 6 Wistar rats were randomly divided into the modified sleeve gastrectomy (modified sleeve gastrectomy, MSG) group, the delayed modified sleeve gastrectomy (delayed-modified sleeve gastrectomy, MSG), the sleeve gastrectomy (sleeve gastrectomy) group, the sham operation group and the sham operation of the group. Group, drug therapy (rosiglitazone, rosiglitazone, RSG) group, restricted diet (food restriction, FR) group, blank control (Controls) group; Wistar rats were constructed as (Wistar MSG, WMSG) group. Dynamic observation of rats in each group during the 16 weeks of surgery: weight, fasting blood glucose, oral glucose tolerance test (OGTT), insulin tolerance Test (ITT); changes in concentration of insulin, Ghrelin, GLP-1, and GIP. In the sixteenth week after operation, the changes in the expression of insulin, Ghrelin, GLP-1 and GIP (pancreas, terminal ileum, duodenum and hypothalamus) and the morphological changes of the pancreas and the distal ileum after operation.
Results: after operation, the glucose tolerance in group MSG was better than that of GK rats in other groups. After second weeks, the area under OGTT in group MSG decreased by 38.9% (P0.001) and 23.9% (P=0.007) compared with SG, while sham-MSG/SG, Controls and FR groups had no more than SG, and the improvement of glucose tolerance in.MSG group 2 weeks after operation was more than that of.MSG group. Before operation (8 weeks after SG), the blood glucose level in group.MSG was obviously better than that of RSG. After operation, the level of Ghrelin in MSG group was obviously better than that in sham group (P0.001), and the level of GLP-1 in MSG group after eating glucose was significantly higher than that in SG and sham group (P0.001). Good (P0.05). 16 weeks after operation, the expression level of insulin and GLP-1 genes in MSG tissues increased significantly, and the form of islets in the MSG group improved obviously. The positive B cell volume and the electronic density of the mature islets in the islets were obviously increased, and the islet cell edema was obviously relieved. These results show that the posterior intestine plays an important role in the regulation of blood glucose. Use.
Conclusion: MSG is a relatively stable, independent operation way to improve blood glucose and improve insulin sensitivity outside the changes of body weight and food intake. MSG further confirms that the cause of type 2 diabetes may be related to the imbalance of various hormones in the body, and the adjustment of the balance of the insulin endocrine axis in the body may be treated as a cure. An effective way to treat diabetes.

【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R656.6;R-332

【参考文献】