糖尿病大鼠袖狀胃切除術(shù)后胃腸動(dòng)力改變及對(duì)GLP-1分泌的影響
發(fā)布時(shí)間:2018-07-11 13:44
本文選題:代謝手術(shù) + 減重手術(shù) ; 參考:《第二軍醫(yī)大學(xué)》2017年碩士論文
【摘要】:研究背景:肥胖和2型糖尿病已成為我國(guó)乃至全球主要的醫(yī)療衛(wèi)生問題。新型代謝手術(shù)袖狀胃切除術(shù)作為肥胖和2型糖尿病患者治療的方法之一,已經(jīng)逐漸被醫(yī)生和患者所認(rèn)可。其手術(shù)操作相對(duì)簡(jiǎn)單,而手術(shù)效果不亞于胃旁路手術(shù)。原有的假說并不能完全解釋袖狀胃切除術(shù)減重降糖的機(jī)制。研究方法:構(gòu)建肥胖糖尿病大鼠模型,隨機(jī)分為袖狀胃切除術(shù)組(SG組,n=10)和假手術(shù)組(S組,n=10),并進(jìn)行相應(yīng)手術(shù)。觀察其體重變化情況;行OGTT試驗(yàn),檢測(cè)其術(shù)前術(shù)后的血糖和胰島素的結(jié)果;用食物稱重法和美蘭灌胃法分別檢測(cè)術(shù)前術(shù)后胃排空率和腸道傳輸率;用RT-PCR法檢測(cè)胃腸道起搏細(xì)胞ICC的特異性標(biāo)記物c-kit mRNA和SCF mRNA轉(zhuǎn)錄水平;用ELISA法檢測(cè)術(shù)后兩組間GLP-1分泌曲線;用免疫組化法檢測(cè)術(shù)后兩組胃腸道L細(xì)胞變化情況;用RT-PCR檢測(cè)胃腸道GLP-1受體mRNA轉(zhuǎn)錄水平。研究結(jié)果:兩組大鼠術(shù)前的體重差異沒有統(tǒng)計(jì)學(xué)意義,SG組術(shù)后的體重顯著低于假手術(shù)組(S組)P≤0.001;術(shù)后SG組大鼠血糖較術(shù)前明顯降低,較術(shù)后S組血糖亦明顯降低,且差異有統(tǒng)計(jì)學(xué)意義。SG組和S組術(shù)后12周的半小時(shí)進(jìn)食量(g)分別為3.70±0.25和4.11±0.56(P=0.049),即SG組術(shù)后大鼠進(jìn)食量小于S組;半小時(shí)胃排空率分別為62.8%±9.0%和52.1%±8.5%(P=0.013),即SG術(shù)后胃半小時(shí)排空比S組增快。腸道傳輸:SG組和S組術(shù)后12周的半小時(shí)腸道傳輸率分別為44.5%±3.7%和35.9%±6.2%(P=0.001),SG術(shù)后腸道傳輸速度比假手術(shù)組快。RT-PCR結(jié)果:不能認(rèn)為兩組大鼠術(shù)后胃竇組織的c-kit mRNA、SCF mRNA轉(zhuǎn)錄水平差異有統(tǒng)計(jì)學(xué)意義,兩組大鼠的空腸和回腸組織c-kit mRNA、SCF mRNA轉(zhuǎn)錄水平差異有統(tǒng)計(jì)學(xué)意義,SG組大鼠的ckit mRNA、SCF mRNA轉(zhuǎn)錄水平較S組增高;術(shù)后SG組大鼠的GLP-1分泌均顯著高于S組。SG組和S組大鼠空腸組織L細(xì)胞免疫組化切片平均光密度(MOD)分別為0.15±0.13和0.13±0.15(P=0.011);回腸組織L細(xì)胞免疫組化切片MOD分別為0.19±0.01和0.18±0.12(P=0.005);SG組大鼠術(shù)后空腸及回腸L細(xì)胞數(shù)量顯著高于S組。研究結(jié)論:(1)肥胖糖尿病大鼠行袖狀胃切除術(shù)后,出現(xiàn)明顯的減重和降糖效果;(2)袖狀胃切除術(shù)后,胃排空增快主要由胃容積減少引起,而小腸蠕動(dòng)增快可能與ICC細(xì)胞增殖有關(guān);(3)袖狀胃切除術(shù)后,腸道L細(xì)胞及GLP-1R數(shù)量增加,腸道蠕動(dòng)增快使得更多未消化的食糜更好地與L細(xì)胞和GLP-1R接觸刺激L細(xì)胞分泌GLP-1,餐后GLP-1分泌高峰與食糜開始接觸末端空腸和回腸的時(shí)間吻合;(4)隨著GLP-1分泌增加及高峰提前,胰島素的分泌高峰也相應(yīng)出現(xiàn)提前,提示SG術(shù)后餐后胰島素分泌及血糖的降低與GLP-1有關(guān);(5)SG組術(shù)后空腹胰島素的分泌比S組少,而對(duì)應(yīng)的血糖同樣降低,提示SG術(shù)后通過改善糖尿病的胰島素抵抗降低血糖,而非刺激胰島素分泌增多。
[Abstract]:Background: obesity and type 2 diabetes have become the major medical and health problems in China and the world. New metabolic surgery cuff gastrectomy as a treatment for obesity and type 2 diabetes has been gradually recognized by doctors and patients. Its operation is relatively simple, and the effect of operation is no less than gastric bypass surgery. The original hypothesis does not fully explain the mechanism of weight loss and glucose reduction in cuff gastrectomy. Methods: the obese diabetic rats were randomly divided into two groups: group SG (group SG) and group S (group S). The changes of body weight were observed, the results of blood glucose and insulin were detected by OGTT test, the gastric emptying rate and intestinal transmission rate were measured by food weighing method and methylene blue gavage method, respectively. The transcription levels of c-kit mRNA and SCF mRNA in gastrointestinal pacemaker cells were detected by RT-PCR, GLP-1 secretion curves were detected by Elisa, the changes of L-cells in gastrointestinal tract were detected by immunohistochemistry. The transcription level of GLP-1 receptor mRNA in gastrointestinal tract was detected by RT-PCR. Results: there was no significant difference in preoperative body weight between the two groups. The body weight in SG group was significantly lower than that in sham operation group (S group) P 鈮,
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