【摘要】：目的:利用正常大鼠(wistar大鼠)建立起保留全胃的胃腸轉流手術(GBP)動物模型,驗證非肥胖型2型糖尿病大鼠(GK大鼠)胃腸轉流手術的可行性,完成GK大鼠的胃腸轉流手術,通過分析三組GK大鼠手術前后體重、空腹血糖水平及胰島功能的變化,探討GBP術對GK大鼠的治療效果和胰島素抵抗的影響。方法:預實驗部分:周齡、體重相近的雄性wistar大鼠共30只,隨機分成2組,每組15只;第1組:對照組(即假手術組),行幽門離斷再吻合術;第2組:手術組(即GBP組),保留全胃行十二指腸加空腸曠置術。記錄兩組手術時間及手術成功率,觀察大鼠術后并發(fā)癥情況及分析死亡原因。正式實驗部分:周齡、體重相近的雄性GK大鼠共30只,隨機分成3組,每組10只;第1組:對照組(即假手術組),行幽門離斷再吻合術;第2組:手術組(即GBP組),保留全胃行十二指腸加空腸曠置術;第3組:空白組,未做手術處理。分別于術前與術后第1、3、6、12周抽取三組GK大鼠尾靜脈血,利用電子秤、血糖儀動態(tài)測定各只大鼠體重和血液中空腹血糖(FPG)水平,應用酶聯免疫吸附試驗(ELISA)檢測各只大鼠手術前后空腹胰島素(FINS)及血清胰高血糖素樣肽-1(GLP-1)的水平,最后計算胰島素抵抗指數(HOMA-IR)。結果:預實驗部分:兩組大鼠總存活率為66.67%,假手術組平均手術時間為75.93±13.58min,術中和術后共死亡6只;GBP組平均手術時間為103.6±11.52min,術中和術后共死亡4只。正式實驗部分:大鼠總存活率為93.33%,假手術組術后第7天死亡1只,GBP組術后第5天死亡1只;與術前相比,術后第1周所有手術大鼠的體重均有所下降,術后第3、6、12周各組GK大鼠體重均明顯增加,差異有統(tǒng)計學意義(P0.05);與術前和同時間點空白組及假手術組相比,GBP組術后FPG值下降,至術后第12周時FPG由14.67±1.73mmol/L下降至5.05±0.42mmol/L,差異有統(tǒng)計學意義(P0.05);與術前和同時間點空白組及假手術組相比,GBP組術后FINS經歷了先升后降的過程,術后1~3周時FINS升高,第6周開始略有下降,至術后12周明顯降低,由14.74±1.01mU/L下降至8.48±1.01mU/L,差異有統(tǒng)計學意義(P0.05);與術前和同時間點空白組及假手術組相比,GBP組術后HOMA-IR持續(xù)下降,由9.59±1.15下降至1.91±0.34,差異有統(tǒng)計學意義(P0.05);與術前和同時間點空白組及假手術組相比,GBP組術后GLP-1水平明顯升高,GLP-1由9.18±0.78pmol/L升高至27.66±0.95pmol/L,差異有統(tǒng)計學意義(P0.05)。結論:1、對大鼠實施保留全胃的胃腸轉流手術是可行的,成功建立起非肥胖型GK大鼠的胃腸轉流手術模型。2、保留全胃的胃腸轉流手術對非肥胖型GK大鼠有明顯的治療效果,能有效降低GK大鼠空腹血糖及改善糖代謝,且與GK大鼠的體重變化無關。3、GBP使食物提前進入回腸,刺激GLP-1的分泌增多,從而達到GBP對T2DM的治療作用。
[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 鹵13.58 minutes, and the average operative time of GBP group was 103.6 鹵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 鹵1.73mmol/L to 5.05 鹵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 鹵1.01mU/L to 8.48 鹵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 鹵0.78pmol/L to 27.66 鹵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.
【學位授予單位】：皖南醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R656.6;R587.1

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