GK大鼠(改良)袖狀胃切除術模型的建立及其降糖作用機制的研究
發(fā)布時間:2018-05-09 00:17
本文選題:改良 + 袖狀胃切除術; 參考:《華中科技大學》2011年博士論文
【摘要】:目的:用GK大鼠建立袖狀胃切除術手術模型,借助此模型來探討袖狀胃切除術(SG)對血糖的控制效果。方法:23只GK大鼠隨機分為袖狀胃切除組(SG)、假手術組(sham-SG)和飲食配對組(PF)。體重、進食量、空腹血糖、口服葡萄糖耐量試驗(OGTT)、胰島素耐量試驗(ITT)和空腹胰島素濃度在特定的時間內(nèi)被檢測。結(jié)果:SG手術模型的成功率為100%。自術后第4周起,SG和PF組與sham-SG組間的體重增量有著明顯的統(tǒng)計學意義(P0.01)。SG組空腹血糖水平較sham-SG和PF組明顯改善。SG組較PF組和sham-SG組明顯改善對葡萄糖耐量的水平,手術后第2周葡萄糖耐量曲線下面積(AUC)較術前減少約28.1%(P0.01),較飲食配對組減少約21%(P0.01)。SG組大鼠術后胰島素耐量和胰島素抵抗指數(shù)(HOMA-IR)較sham-SG和PF組明顯改善。結(jié)論:SG能夠直接控制2型糖尿病而不是繼發(fā)于體重減輕的效果。SG是一種相對穩(wěn)定的降糖手術模型。 目的:探討袖狀胃切除術的降糖作用及其機制。方法:隨機將GK大鼠分為袖狀胃切除(SG)組、假手術(sham-SG)組、飲食配對(PF)組和空白對照(Control)組。動態(tài)觀察手術前和手術后24周中各組大鼠體重、空腹血糖、口服葡萄糖耐量試驗(OGTT)、胰島素耐量試驗(ITT)、胰島素、Ghrelin及GLP-1濃度的變化。結(jié)果:自術后第4周起,SG和PF組與sham-SG和Control組之間的體重增量有明顯統(tǒng)計學意義(P0.01)。術后SG組空腹血糖濃度較其它3組明顯降低(P0.05),SG組術后第2周OGTT曲線下面積(AUC)較其術前減少約28.1%(P0.01),相對于其它3組有顯著性的差異(P0.05)。術后第6周的ITT顯示SG組胰島素敏感性較sham-SG組明顯改善,血糖水平變化明顯降低。實驗期間,與sham-SG組相比,SG組胰島素濃度無明顯變化(P0.05), Ghrelin濃度明顯下降(P0.01), GLP-1濃度上升(P0.01)。結(jié)論:SG降糖效果確切,能夠獨立于體重的變化而直接有效地降低血糖。術后Ghrelin濃度下降、GLP-1濃度升高可能是SG降糖的主要機制。 目的:建立胃袖狀切除附加改良空回腸旁路的GK大鼠模型并對其分析。方法:將27只GK大鼠隨機分為改良胃袖狀切術(MSG)組、假手術(sham-MSG)組、飲食配對組(PF)組和空白對照(Controls)組。動態(tài)觀察手術前和手術后16周體重、空腹血糖、口服葡萄糖耐量試驗(OGTT)、胰島素濃度、胰島素抵抗指數(shù)(HOMA-IR)及其體內(nèi)血脂水平的變化。結(jié)果:從手術后第4周起MSG與sham-MSG和PF組的體重增量有明顯統(tǒng)計學差異(P0.01)。MSG組空腹血糖濃度較其它3組明顯降低。術后第2周MSG組的OGTT曲線下面積(AUC)較術前減少約38.9%(P0.01),而在sham-MSG和PF組卻無以上明顯變化。實驗期間,MSG組胰島素敏感性及其分泌量明顯改善,而在sham-MSG組卻無以上明顯變化。與PF組和sham-MSG組相比,MSG組在術后的血脂濃度得到明顯改善。這些結(jié)果顯示后腸在血糖調(diào)節(jié)中可能起到了重要的作用。結(jié)論:MSG獨立于體重和進食量的變化直接控制GK大鼠體內(nèi)血糖水平,為2型糖尿病治療機制的研究提供了一種穩(wěn)定、持久的降糖手術模型。 目的:研究改良袖狀胃切除術的降糖作用,并對其降糖機制進行初步探討。 方法:54只GK大鼠和6只Wistar大鼠隨機分為改良袖狀胃切除(modified sleeve gastrectomy, MSG)組,延遲-改良袖狀胃切除(delayed-modified sleeve gastrectomy,MSG)組,袖狀胃切除(sleeve gastrectomy, SG)組,對應MSG組的假手術(sham-MSG)組,對應SG組的假手術(sham-SG)組,藥物治療(羅格列酮,rosiglitazone, RSG)組,限制飲食(food restriction, FR)組;空白對照(Controls)組;Wistar大鼠構建為(Wistar MSG, WMSG)組。動態(tài)觀察手術前后16周中各組大鼠對應的檢測項目:體重、空腹血糖、口服葡萄糖耐量試驗(OGTT)、胰島素耐量試驗(ITT);胰島素、Ghrelin、GLP-1和GIP濃度的變化。在術后第16周,組織中insulin、Ghrelin、GLP-1和GIP(胰腺、末端回腸、十二指腸和下丘腦)對應基因表達的變化水平及其手術后胰腺和末端回腸等組織的形態(tài)學變化。 結(jié)果:手術后,MSG組對葡萄糖耐量較其它各組的GK大鼠明顯改善。術后第2周,MSG組行OGTT后的曲線下面積較術前減少38.9%(P0.001),較SG減少23.9%(P=0.007),而sham-MSG/SG、Controls和FR組都沒有以上的變化發(fā)生。MSG組術后2周對葡萄糖耐量的改善程度較該組術前(SG術后8周)明顯。MSG組行ITT后血糖水平變化較RSG改善明顯。術后,MSG組空腹血漿Ghrelin水平較假手術組明顯改善(P0.001),MSG組進食葡萄糖后血漿GLP-1水平較SG和假手術組明顯升高(P0.001)。術后MSG組胰島素水平較SG和假手術組明顯改善(P0.05)。術后16周,MSG組織中的胰島素和GLP-1基因的表達水平明顯上升,并且MSG組胰島形態(tài)明顯改善,陽性B細胞量和胰島內(nèi)成熟腺泡的電子密度都明顯增加,胰島細胞水腫現(xiàn)象明顯緩解。這些結(jié)果顯示后腸在血糖調(diào)節(jié)中起到了重要的作用。 結(jié)論:MSG是一種相對穩(wěn)定的、獨立與體重和進食量的變化外直接改善血糖并改善胰島素敏感性的一種手術方式;MSG進一步證實了2型糖尿病的病因可能與體內(nèi)多種激素分泌的失衡有關,重新調(diào)節(jié)體內(nèi)胰島素內(nèi)分泌軸的平衡可能是治療糖尿病的有效方法。
[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.
【學位授予單位】:華中科技大學
【學位級別】:博士
【學位授予年份】:2011
【分類號】:R656.6;R-332
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