GK大鼠胃肠转流手术模型建立及其胰岛功能改变的实验研究
发布时间：2018-10-14 12:14
【摘要】：目的:利用正常大鼠(wistar大鼠)建立起保留全胃的胃肠转流手术(GBP)动物模型,验证非肥胖型2型糖尿病大鼠(GK大鼠)胃肠转流手术的可行性,完成GK大鼠的胃肠转流手术,通过分析三组GK大鼠手术前后体重、空腹血糖水平及胰岛功能的变化,探讨GBP术对GK大鼠的治疗效果和胰岛素抵抗的影响。方法:预实验部分:周龄、体重相近的雄性wistar大鼠共30只,随机分成2组,每组15只;第1组:对照组(即假手术组),行幽门离断再吻合术;第2组:手术组(即GBP组),保留全胃行十二指肠加空肠旷置术。记录两组手术时间及手术成功率,观察大鼠术后并发症情况及分析死亡原因。正式实验部分:周龄、体重相近的雄性GK大鼠共30只,随机分成3组,每组10只;第1组:对照组(即假手术组),行幽门离断再吻合术;第2组:手术组(即GBP组),保留全胃行十二指肠加空肠旷置术;第3组:空白组,未做手术处理。分别于术前与术后第1、3、6、12周抽取三组GK大鼠尾静脉血,利用电子秤、血糖仪动态测定各只大鼠体重和血液中空腹血糖(FPG)水平,应用酶联免疫吸附试验(ELISA)检测各只大鼠手术前后空腹胰岛素(FINS)及血清胰高血糖素样肽-1(GLP-1)的水平,最后计算胰岛素抵抗指数(HOMA-IR)。结果:预实验部分:两组大鼠总存活率为66.67%,假手术组平均手术时间为75.93±13.58min,术中和术后共死亡6只;GBP组平均手术时间为103.6±11.52min,术中和术后共死亡4只。正式实验部分:大鼠总存活率为93.33%,假手术组术后第7天死亡1只,GBP组术后第5天死亡1只;与术前相比,术后第1周所有手术大鼠的体重均有所下降,术后第3、6、12周各组GK大鼠体重均明显增加,差异有统计学意义(P0.05);与术前和同时间点空白组及假手术组相比,GBP组术后FPG值下降,至术后第12周时FPG由14.67±1.73mmol/L下降至5.05±0.42mmol/L,差异有统计学意义(P0.05);与术前和同时间点空白组及假手术组相比,GBP组术后FINS经历了先升后降的过程,术后1~3周时FINS升高,第6周开始略有下降,至术后12周明显降低,由14.74±1.01mU/L下降至8.48±1.01mU/L,差异有统计学意义(P0.05);与术前和同时间点空白组及假手术组相比,GBP组术后HOMA-IR持续下降,由9.59±1.15下降至1.91±0.34,差异有统计学意义(P0.05);与术前和同时间点空白组及假手术组相比,GBP组术后GLP-1水平明显升高,GLP-1由9.18±0.78pmol/L升高至27.66±0.95pmol/L,差异有统计学意义(P0.05)。结论:1、对大鼠实施保留全胃的胃肠转流手术是可行的,成功建立起非肥胖型GK大鼠的胃肠转流手术模型。2、保留全胃的胃肠转流手术对非肥胖型GK大鼠有明显的治疗效果,能有效降低GK大鼠空腹血糖及改善糖代谢,且与GK大鼠的体重变化无关。3、GBP使食物提前进入回肠,刺激GLP-1的分泌增多,从而达到GBP对T2DM的治疗作用。
[Abstract]:Objective: to establish a (GBP) animal model of gastrointestinal bypass surgery in normal rats (wistar rats), to verify the feasibility of gastroenteric bypass surgery in non-obese type 2 diabetic rats (GK rats), and to complete gastrointestinal bypass surgery in GK rats. By analyzing the changes of body weight, fasting blood glucose level and islet function in three groups of GK rats before and after operation, the therapeutic effect of GBP on GK rats and the effect of insulin resistance were discussed. Methods: 30 male wistar rats of similar body weight were randomly divided into 2 groups (15 rats in each group): the control group (sham-operated group) was treated with pylorus break and reanastomosis, and the control group (sham operation group) was divided into two groups: the control group (sham operation group), the control group (sham operation group). Group 2: operation group (GBP group), the whole stomach was treated with duodenum plus jejunum. The operative time and success rate were recorded and the postoperative complications were observed and the causes of death were analyzed. In the formal experiment, 30 male GK rats of similar body weight were randomly divided into 3 groups, 10 rats in each group, group 1: control group (sham-operation group), pyloric rupture and reanastomosis; Group 2: operation group (GBP group), the whole stomach was treated with duodenum plus jejunum open place, group 3: blank group, without operation. Caudal venous blood samples were drawn from three groups of GK rats before operation and at 612 weeks after operation. The body weight and fasting blood glucose (FPG) levels in each group were measured by electronic scale and glycometer. Fasting insulin (FINS) and serum glucagon like peptide-1 (GLP-1) levels were measured by enzyme linked immunosorbent assay (ELISA) before and after operation in each rat. Finally, insulin resistance index (HOMA-IR) was calculated. Results: the total survival rate of the two groups was 66.67, the mean operation time of sham operation group was 75.93 卤13.58 minutes, and the average operative time of GBP group was 103.6 卤11.52 minutes, 4 rats died during and after operation. In the formal experiment, the total survival rate of the rats was 93.33. One rat died on the 7th day after operation in the sham operation group, and one died on the fifth day after the operation in the GBP group. The body weight of GK rats in all groups increased significantly at 12 weeks after operation (P0.05). Compared with the blank group and sham-operation group, the FPG value of GBP group decreased significantly after 12 weeks (P < 0.05), and compared with the control group and sham operation group at the same time point before operation and at the same time point. The FPG decreased from 14.67 卤1.73mmol/L to 5.05 卤0.42mmol / L at the 12th week after operation (P0.05). Compared with the blank group and sham operation group, the FINS in GBP group increased first and then decreased, and increased at 1 and 3 weeks after operation, and decreased slightly at the 6th week. At the 12th week after operation, the HOMA-IR decreased significantly from 14.74 卤1.01mU/L to 8.48 卤1.01mU / L (P0.05). Compared with the blank group and sham operation group, the HOMA-IR of GBP group decreased continuously. Compared with the control group and sham operation group, the level of GLP-1 in GBP group increased significantly, GLP-1 increased from 9.18 卤0.78pmol/L to 27.66 卤0.95pmol / L (P0.05). Conclusion: 1. It is feasible to carry out the gastrointestinal bypass surgery for the whole stomach in rats, and establish the gastrointestinal bypass operation model of the non-obese GK rats successfully. 2. The gastrointestinal bypass operation with the whole stomach preservation has obvious therapeutic effect on the non-obese GK rats. It can effectively reduce fasting blood glucose and improve glucose metabolism in GK rats, and has no relation to the change of body weight of GK rats. 3GBP can advance food into ileum and stimulate the secretion of GLP-1 to achieve the therapeutic effect of GBP on T2DM.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R656.6;R587.1
本文编号：2270421
[Abstract]:Objective: to establish a (GBP) animal model of gastrointestinal bypass surgery in normal rats (wistar rats), to verify the feasibility of gastroenteric bypass surgery in non-obese type 2 diabetic rats (GK rats), and to complete gastrointestinal bypass surgery in GK rats. By analyzing the changes of body weight, fasting blood glucose level and islet function in three groups of GK rats before and after operation, the therapeutic effect of GBP on GK rats and the effect of insulin resistance were discussed. Methods: 30 male wistar rats of similar body weight were randomly divided into 2 groups (15 rats in each group): the control group (sham-operated group) was treated with pylorus break and reanastomosis, and the control group (sham operation group) was divided into two groups: the control group (sham operation group), the control group (sham operation group). Group 2: operation group (GBP group), the whole stomach was treated with duodenum plus jejunum. The operative time and success rate were recorded and the postoperative complications were observed and the causes of death were analyzed. In the formal experiment, 30 male GK rats of similar body weight were randomly divided into 3 groups, 10 rats in each group, group 1: control group (sham-operation group), pyloric rupture and reanastomosis; Group 2: operation group (GBP group), the whole stomach was treated with duodenum plus jejunum open place, group 3: blank group, without operation. Caudal venous blood samples were drawn from three groups of GK rats before operation and at 612 weeks after operation. The body weight and fasting blood glucose (FPG) levels in each group were measured by electronic scale and glycometer. Fasting insulin (FINS) and serum glucagon like peptide-1 (GLP-1) levels were measured by enzyme linked immunosorbent assay (ELISA) before and after operation in each rat. Finally, insulin resistance index (HOMA-IR) was calculated. Results: the total survival rate of the two groups was 66.67, the mean operation time of sham operation group was 75.93 卤13.58 minutes, and the average operative time of GBP group was 103.6 卤11.52 minutes, 4 rats died during and after operation. In the formal experiment, the total survival rate of the rats was 93.33. One rat died on the 7th day after operation in the sham operation group, and one died on the fifth day after the operation in the GBP group. The body weight of GK rats in all groups increased significantly at 12 weeks after operation (P0.05). Compared with the blank group and sham-operation group, the FPG value of GBP group decreased significantly after 12 weeks (P < 0.05), and compared with the control group and sham operation group at the same time point before operation and at the same time point. The FPG decreased from 14.67 卤1.73mmol/L to 5.05 卤0.42mmol / L at the 12th week after operation (P0.05). Compared with the blank group and sham operation group, the FINS in GBP group increased first and then decreased, and increased at 1 and 3 weeks after operation, and decreased slightly at the 6th week. At the 12th week after operation, the HOMA-IR decreased significantly from 14.74 卤1.01mU/L to 8.48 卤1.01mU / L (P0.05). Compared with the blank group and sham operation group, the HOMA-IR of GBP group decreased continuously. Compared with the control group and sham operation group, the level of GLP-1 in GBP group increased significantly, GLP-1 increased from 9.18 卤0.78pmol/L to 27.66 卤0.95pmol / L (P0.05). Conclusion: 1. It is feasible to carry out the gastrointestinal bypass surgery for the whole stomach in rats, and establish the gastrointestinal bypass operation model of the non-obese GK rats successfully. 2. The gastrointestinal bypass operation with the whole stomach preservation has obvious therapeutic effect on the non-obese GK rats. It can effectively reduce fasting blood glucose and improve glucose metabolism in GK rats, and has no relation to the change of body weight of GK rats. 3GBP can advance food into ileum and stimulate the secretion of GLP-1 to achieve the therapeutic effect of GBP on T2DM.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R656.6;R587.1
【参考文献】
相关期刊论文 前10条
1 安东均;郑晓燕;安琳;张成;王羊;;腹腔镜手术治疗胆囊结石合并低体质量指数2型糖尿病[J];中华普通外科杂志;2016年11期
2 邵得志;冯志毅;张海生;王晓翠;富忱;;180例胃转流手术治疗2型糖尿病术后并发症防治体会[J];中华普外科手术学杂志(电子版);2016年03期
3 高寅生;侯亚勃;杨晓军;高鹏;曹农;;胃饥饿素/肽YY/刺鼠相关蛋白信号在胃旁路手术治疗2型糖尿病中的作用[J];中华实验外科杂志;2016年05期
4 颜勇;李旭忠;王时光;周联明;瞿军;周舟;胡承;张学利;;减重手术治疗伴肥胖2型糖尿病作用机制的研究进展[J];医学研究杂志;2016年02期
5 侯清涛;李芸;李舍予;田浩明;;全球糖尿病疾病负担现状[J];中国糖尿病杂志;2016年01期
6 汪会琴;胡如英;武海滨;俞敏;;2型糖尿病报告发病率研究进展[J];浙江预防医学;2016年01期
7 郎敏;张宏斌;吴良平;黄宗海;;减重手术治疗2型糖尿病机制研究进展[J];中华腔镜外科杂志(电子版);2015年05期
8 何洪兴;;外科手术治疗2型糖尿病的机制[J];中华临床医师杂志(电子版);2015年19期
9 张振;宫轲;;外科治疗糖尿病的主要手术方式及其机制[J];首都医科大学学报;2015年02期
10 刘金刚;郑成竹;王勇;;中国肥胖和2型糖尿病外科治疗指南(2014)[J];中国实用外科杂志;2014年11期
相关博士学位论文 前3条
1 湛奕;胰高血糖素样肽-1对糖基化终产物诱导内皮细胞凋亡的影响及机制[D];南方医科大学;2012年
2 李峰;胃肠道重组对非肥胖2型糖尿病治疗作用及机制的动物实验研究[D];山东大学;2010年
3 季新荣;外科手术治疗肥胖和2型糖尿病机制的研究[D];第二军医大学;2010年
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