本文選題：五甲基槲皮素　切入點：STZ　出處：《華中科技大學(xué)》2011年博士論文

【摘要】：T2DM是最常見的內(nèi)分泌代謝紊亂性疾病之一,近年來其發(fā)病率在全世界范圍內(nèi)迅速攀升。T2DM在臨床上主要以外周組織對胰島素的敏感性進(jìn)行性下調(diào)且胰腺β細(xì)胞凋亡壞死及其功能持續(xù)性衰退為主要病理生理表現(xiàn)。基于T2DM的流行病學(xué)特點,近年來有關(guān)T2DM的病因?qū)W、病理生理學(xué)及其治療學(xué)的研究在全世界范圍內(nèi)開展得如火如荼。 五甲基槲皮素是天然多甲氧基黃酮家族(PMF)的成員之一,也是槲皮素的甲基化衍生物之一,主要存在于沙棘果中。大量研究結(jié)果表明,PMF家族成員具有多種藥理活性,如抗糖尿病、抗炎等；相應(yīng)的,也有文獻(xiàn)報道PMQ具有抗腫瘤、抗心肌肥厚等作用,然而迄今為止,有關(guān)PMQ調(diào)節(jié)機體糖脂代謝穩(wěn)態(tài)的研究還未見諸報道。 胃袖狀切除術(shù)原是外科減肥手術(shù)的一部分,由于其具有手術(shù)時間短、難度低、術(shù)后并發(fā)癥少等特點而廣受外科醫(yī)生和病患的青睞。有研究結(jié)果表明,胃袖狀切除術(shù)在減肥的同時還可顯著降低肥胖患者顯著升高的血糖水平,改善胰島素抵抗,調(diào)節(jié)脂代謝紊亂等。 鑒于以上研究基礎(chǔ),我們設(shè)想：PMQ及胃袖狀切除術(shù)在乳鼠腹腔注射STZ誘導(dǎo)T2DM大鼠模型中是否也具有改善糖脂代謝紊亂的作用呢?據(jù)此,本研究主要分為三個部分。 第一部分乳鼠腹腔注射STZ誘導(dǎo)2型糖尿病大鼠模型的建立 目的：建立乳鼠腹腔注射STZ誘導(dǎo)T2DM大鼠模型并掌握其基本特點,為后期研究打下基礎(chǔ)。方法：于華中科技大學(xué)同濟(jì)醫(yī)學(xué)院動物飼養(yǎng)中心購回健康SD大鼠(160-180 g,雌性大鼠數(shù)量：雄性大鼠數(shù)量=2：1)正常飼養(yǎng),至雌性大鼠體重達(dá)280 g且雄性大鼠體重達(dá)350 g左右時按照1雄2雌比例進(jìn)行配種,期間正常飼養(yǎng),保持飼養(yǎng)間溫度22±2℃,濕度50±5%及12h光照周期,并密切跟蹤觀察雌性大鼠的體重及體型。于雌性大鼠產(chǎn)前3天將其提出分籠,單獨飼養(yǎng)。雄性乳鼠出生后48±2h內(nèi)腹腔注射STZ(90mg/kg)。待乳鼠28日齡時斷乳分籠,正常飼養(yǎng),于其6、8、10、12、14及16周齡時檢測其空腹及餐后血糖、甘油三酯、膽固醇、胰島素及體重水平,以掌握該模型的基本特征。結(jié)果：按此方法造模,模型鼠成年后狀態(tài)較好,但體重顯著性降低,空腹血糖水平進(jìn)行性升高,餐后血糖及餐后甘油三酯水平顯著高于正常大鼠,空腹甘油三酯水平、空腹和餐后膽固醇水平升高不明顯,空腹胰島素水平顯著性降低。結(jié)論：乳鼠腹腔注射STZ誘導(dǎo)T2DM大鼠模型較好的模擬了人類T2DM的病理生理特征及其典型病程,即疾病早期主要表現(xiàn)為顯著升高的餐后血糖水平及糖耐量受損,后期空腹血糖水平升高且伴有明顯的脂代謝紊亂。該模型的成模率為100%,是一種較理想的T2DM動物模型,可為抗糖尿病新藥的初期篩選提供理想平臺。 第二部分PMQ對乳鼠腹腔注射STZ誘導(dǎo)2型糖尿病大鼠模型的藥效學(xué)研究 目的：于乳鼠腹腔注射STZ誘導(dǎo)2型糖尿病大鼠模型中篩選PMQ是否具有改善糖脂代謝紊亂的作用。方法：實驗分為六組(n=9-12)：正常對照組；糖尿病組(模型對照組)；PMQ各劑量組(模型鼠分別灌胃給予PMQ 2.5,5,10,20mg/kg)。各組大鼠自6周齡開始給藥,給藥時間定為每日8：30 a.m.,持續(xù)10周。正常對照組和糖尿病組大鼠給予藥物溶劑灌胃給藥。本研究中所選PMQ劑量是基于本實驗室前期PMQ于大鼠體內(nèi)藥代動力學(xué)特征的實驗結(jié)果。給藥期間每日稱取大鼠體重,并跟蹤記錄其飲水和進(jìn)食量。分別在大鼠12和16周齡(給藥后6和10周)時檢測各組大鼠空腹及餐后血糖、甘油三酯和胰島素水平。給藥結(jié)束后進(jìn)行OGTT實驗,宰殺大鼠取肝、胰腺、腎臟等器官,計算器官指數(shù),并做胰腺組織切片行HE染色。結(jié)果：PMQ給藥可劑量依賴性地降低模型大鼠顯著升高的餐后血糖和甘油三酯水平,延緩其空腹血糖水平的升高,改善糖尿病大鼠的多飲多食癥狀及其糖耐量受損程度,顯著上調(diào)外周組織的胰島素敏感性,降低糖尿病大鼠異常升高的血清谷丙轉(zhuǎn)氨酶水平。結(jié)論：PMQ在乳鼠腹腔注射STZ誘導(dǎo)T2DM大鼠模型中表現(xiàn)出顯著的改善糖脂代謝紊亂的作用。 第三部分胃袖狀切除術(shù)對乳鼠腹腔注射STZ誘導(dǎo)2型糖尿病大鼠模型的效應(yīng)研究 目的：研究胃袖狀切除術(shù)于乳鼠腹腔注射STZ誘導(dǎo)T2DM大鼠模型中對模型大鼠體重及其糖代謝的影響。方法：實驗分為手術(shù)組(n=6)和假手術(shù)組(n=6)。模型大鼠術(shù)前禁食12h,可自由攝水。大鼠腹腔注射苯巴比妥鈉(40 mg/kg),待動物麻醉好后將其仰面固定于動物手術(shù)臺上,術(shù)前30min預(yù)防性肌注青霉素G(50 mg/kg)以防止術(shù)后感染。備皮,沿腹中線做一長約3-4厘米的切口,分離皮膚及肌肉層,小心將胃游離出來,用無創(chuàng)性止血鉗沿胃大彎將胃固定,用無菌外科手術(shù)刀片沿著胃大彎切除約70%-80%體積的胃組織,殘胃用碘伏擦拭消毒后用5-0規(guī)格手術(shù)線縫合,縫合結(jié)束后松開無創(chuàng)止血鉗,檢查縫合效果,如有出血點適當(dāng)補針。手術(shù)完畢后用無菌生理鹽水沖洗腹腔,最后用3-0規(guī)格手術(shù)線縫合腹腔。假手術(shù)組與手術(shù)組步驟基本相同,但并不切除胃組織。各組大鼠術(shù)后恢復(fù)一周,至第2周開始每周記錄其體重、進(jìn)食和飲水量,術(shù)后第4周和第8周兩個時間點分別檢測大鼠空腹和餐后血糖水平,實驗結(jié)束時檢測各組大鼠空腹胰島素、GIP、活性GLP-1及ghrelin水平。結(jié)果：與假手術(shù)組相比,胃袖狀切除術(shù)可顯著控制模型大鼠術(shù)后的體重增長,減少其飲水和進(jìn)食量,但胃袖狀切除術(shù)在乳鼠腹腔注射STZ誘導(dǎo)T2DM大鼠模型中沒有明顯的改善糖代謝紊亂的作用,相應(yīng)的,兩組大鼠糖代謝相關(guān)激素如GLP-1、GIP和胰島素水平?jīng)]有統(tǒng)計學(xué)差異。與假手術(shù)組大鼠相比,SG術(shù)后手術(shù)組大鼠的ghrelin水平顯著降低。結(jié)論：胃袖狀切除術(shù)可顯著控制大鼠體重,但不能改善乳鼠腹腔注射STZ誘導(dǎo)T2DM大鼠的糖代謝紊亂。
[Abstract]:T2DM is one of the most common endocrine and metabolic disorders in the world . In recent years , the incidence of T2DM has been increasing rapidly worldwide . In recent years , the sensitivity of T2DM to insulin has been downregulated and the necrosis of pancreatic 尾 - cell apoptosis and its function continue to decline . Based on the epidemiological characteristics of T2DM , the study of etiology , physiopathology and therapeutics of T2DM in recent years has been in full swing around the world .


The pentamethylquercetin is one of the members of the natural polymethoxyflavone family ( PMF ) , also one of the methylated derivatives of quercetin , which is mainly found in the fruit of sea buckthorn . The results show that the PMF family members have various pharmacological activities , such as anti - diabetes , anti - inflammation , etc .
It is also reported that PMQ has anti - tumor and anti - myocardial hypertrophy . So far , the study of PMQ regulating the steady state of glycolipid metabolism has not been reported .


The gastrectomy is a part of the surgical weight - losing operation , because it has the characteristics of short operation time , low difficulty , less postoperative complications and so on . The results show that the gastrectomy can significantly reduce the blood sugar level , improve insulin resistance , regulate lipid metabolism disorder , etc . , while losing weight .


In view of the above research foundation , it is envisaged that PMQ and gastrectomy can improve the metabolism of glycolipids in the model of rats with T2DM induced by intraperitoneal injection in rats .


Establishment of Model 2 Diabetic Rat Model Induced by Intraperitoneal Injection of Diabetic Mice


Objective : To establish a model of rats with T2DM induced by intraperitoneal injection of diabetic rats and to grasp the basic characteristics of rats . The results showed that the rats with T2DM induced T2DM were fed with intraperitoneal injection ( 90 mg / kg ) at the age of 6 , 8 , 10 , 12 , 14 and 16 .


Effect of the second PMQ on the model of 2 - type diabetic rats induced by intraperitoneal injection in rats


Objective : To investigate whether PMQ has the effect of improving the metabolism of glycolipids in rats with type 2 diabetes induced by intraperitoneal injection in rats . Methods : The experiment was divided into six groups ( n = 9 - 12 ) : normal control group ;
Diabetic group ( model control group ) ;
PMQ 2.5 , 5 , 10 , 20 mg / kg was administered in each dose group of PMQ ( model mice respectively ) . Plasma glucose , triglyceride and insulin levels were measured in rats at 12 and 16 weeks of age ( 6 and 10 weeks after administration ) .


Effect of third partial gastrectomy on model of 2 - type diabetic rats induced by intraperitoneal injection in rats


Objective : To study the effects of gastric sleeve resection on body weight and glucose metabolism in rats with T2DM induced by intraperitoneal injection in rats . Methods : The rats were divided into two groups : operation group ( n = 6 ) and sham operation group ( n = 6 ) .

【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R285.5;R-332

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 周芳;彭朵花;杜方麓;;多甲氧基黃酮的化學(xué)成分及藥理作用研究進(jìn)展[J];中南藥學(xué);2008年06期

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本文編號：1716522