發(fā)布時間：2018-02-04 02:18

  本文關(guān)鍵詞： 2型糖尿病 黃芪多糖 物質(zhì)代謝 并發(fā)癥　出處：《新鄉(xiāng)醫(yī)學(xué)院》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：背景糖尿病是由于胰島素分泌不足或(和)胰島素抵抗所引起的一種以血糖持續(xù)高水平為特征的代謝綜合征。持續(xù)較高水平的血糖可導(dǎo)致一系列器官或組織的損害,如脂肪代謝紊亂、腎臟、心臟、眼、神經(jīng)功能損害等。黃芪多糖(Astragalus polysaecharides,APS),目前研究認(rèn)為其具有抗衰老、增強免疫力、防止脂質(zhì)過氧化以及改善腎功能等作用。本文通過觀察APS對調(diào)節(jié)糖尿病大鼠血糖水平、改善血脂及腎臟功能的作用,進(jìn)而分析APS在糖尿病治療中的臨床價值。目的通過腹腔注射40 mg/kg鏈脲佐菌素(Streptozotocin,STZ)和高脂高糖飼料喂養(yǎng)方式,建立2型糖尿病大鼠模型。密切觀察給予不同干預(yù)的2型糖尿病大鼠血糖水平、血脂水平以及相關(guān)肝腎臟指標(biāo)變化,進(jìn)一步探討分析黃芪多糖在治療糖尿病及預(yù)防并發(fā)癥中的臨床價值。方法選擇健康狀況良好的6周齡Wistar大鼠共90只,雄性,體重為180±15g,均由新鄉(xiāng)醫(yī)學(xué)院醫(yī)學(xué)實驗動物中心提供。相同環(huán)境下分籠飼養(yǎng),自由光照,充足飲食,各組進(jìn)食量無明顯差異。飼養(yǎng)室的溫度保持在23±2℃,濕度維持在41%±15%。實驗開始前,隨機抽取60只分為B組和C組,將B組和C組大鼠采用高脂高糖飲食飼養(yǎng)6周,之后給予腹腔注射鏈脲佐菌素。通過腹腔注射40 mg/kg鏈脲佐菌素以及高脂高糖飼養(yǎng)方式建立2型糖尿病大鼠模型,造模過程中,T2DM組大鼠13.3%動物死亡(8/60),52只存活大鼠中4只血糖不達(dá)標(biāo),予以剔除,最終成模48只。并隨機分為模型對照組(B組)和APS組(C組);余30只中隨機抽取24只為正常對照組(A組)。C組大鼠給予APS 400 mg/kg/d灌胃,A、C組分別給予等量生理鹽水。分別于實驗第0、2、4、6周分別自各組隨機抓取6只大鼠,代謝籠法收集24小時尿液;禁食12小時,晨起取尾靜脈血檢測空腹血糖值大于等于16.7mmol/l則表示造模成功。然后給予相同飼料喂養(yǎng),于進(jìn)食后0.5、1.0、1.5以及2.0小時再次分別檢測血糖值�；铙w心臟采血5ml,制備血清,檢測tc、tg、alt、ast、sod以及mda水平。另分別取肝、腎組織,制備石蠟切片或透射電鏡切片,染色觀察。采用spss19.0統(tǒng)計軟件對相關(guān)實驗數(shù)據(jù)進(jìn)行分析,比較3組實驗動物不同時間點各指標(biāo)差異。組內(nèi)比較采用配對t檢驗,組間兩兩比較采用獨立樣本t檢驗,α=0.05,p0.05表示差異有統(tǒng)計學(xué)意義。結(jié)果1.空腹血糖水平:隨實驗時間延長,b組大鼠glu水平呈緩慢上升趨勢,c組大鼠glu水平則自第2周始呈下降趨勢。組內(nèi)比較:b組第4、6周時glu水平與第0周無顯著差異(p0.05),而c組相同時間點glu水平則顯著低于第0周(p0.05)。組間比較:第0、2周時,c組glu水平顯著高于a組(p0.05),但與b組無顯著差異(p0.05);而在第4、6周時,c組glu水平顯著高于a組(p0.05),且低于b組(p0.05)。2.血脂水平的比較:第2、4、6周時,b、c組大鼠tc、tg水平均較a組明顯上升(p0.05)。組內(nèi)比較:第4、6周時,b、c大鼠tc、tg水平均顯著高于第0周(p0.05)。組間比較:第2周時,c組大鼠tc、tg水平均高于a組(p0.05),但與b組無顯著差異(p0.05);第4、6周時,c組大鼠tc、tg水平均高于a組(p0.05),且低于b組(p0.05)。3.腎功能指標(biāo)的比較:尿微量白蛋白:試驗期間a組大鼠尿微量白蛋白水平未見明顯變化,b組大鼠尿微量白蛋白水平緩慢上升,而c組大鼠各時間點尿微量白蛋白水平均低于b組,且呈下降趨勢。統(tǒng)計學(xué)分析發(fā)現(xiàn),c組大鼠第2、4、6周尿微量白蛋白水平均顯著高于a組(p0.05),但低于b組(p0.05)。腎組織形態(tài)學(xué)變化:實驗第2周時,三組大鼠腎臟組織切片he染色觀察未見明顯異常。第4周時,b、c組大鼠腎臟組織切片he染色觀察可見輕微腎小管損傷,局部炎癥表現(xiàn)。第6周時,b組大鼠腎小管囊腔出現(xiàn)增大表現(xiàn),形態(tài)改變;腎小管上皮細(xì)胞可見炎性腫大。c組大鼠腎小管上皮細(xì)胞可見輕微炎癥表現(xiàn),局部腎小管內(nèi)可見較為少量蛋白聚集。A組大鼠未見明顯異常。4.肝臟指標(biāo)比較:血清學(xué)指標(biāo):第0、2周時B、C組大鼠ALT、AST、SOD以及MDA水平比較無顯著差異(P0.05)。第4、6周時,C組大鼠ALT、AST以及MDA水平均高于A組,但低于B組;而SOD水平低于A組,但高于B組;差異均有統(tǒng)計學(xué)意義(P0.05)。肝組織形態(tài)學(xué)觀察:HE染色:第2、4周時,三組大鼠肝臟組織切片HE染色觀察未見明顯異常。第0、2、4周時各組大鼠肝索排列規(guī)則,肝細(xì)胞結(jié)構(gòu)完整,肝小葉結(jié)構(gòu)顯示清楚,肝竇存在,鏡下未見肝細(xì)胞變性、壞死性病變。第6周時,B組大鼠肝組織局部肝細(xì)胞腫脹明顯,細(xì)胞核變小,深染,胞內(nèi)可見輕度空泡變性;部分肝小葉輪廓發(fā)生較為明顯的改變,肝竇明顯變窄,部分甚至消失不見,小葉間及匯管區(qū)可見血管擴(kuò)張淤血。C組大鼠肝組織切片可見肝細(xì)胞輕度腫大,未見明顯的肝細(xì)胞空泡樣變性;肝小葉結(jié)構(gòu)較為清晰,肝竇較前變窄,小葉間以及匯管區(qū)血管可見輕度擴(kuò)張。透射電鏡觀察:實驗第2、4周時,B組和C組大鼠肝細(xì)胞超微結(jié)構(gòu)無明顯變化,細(xì)胞器完整,各細(xì)胞器如內(nèi)質(zhì)網(wǎng)、線粒體等豐富,糖原輕度減少,基質(zhì)輕度腫脹,脂滴明顯可見。第6周時,B組大鼠肝細(xì)胞腫脹變形,線粒體減少且明顯腫脹,部分線粒體出現(xiàn)空泡化,膜、嵴均有溶解,斷裂現(xiàn)象;粗面內(nèi)質(zhì)網(wǎng)擴(kuò)張、斷裂,膜結(jié)構(gòu)損壞。細(xì)胞內(nèi)脂滴明顯增加,糖原顯著減少。C組大鼠損傷程度較B組為輕。A組大鼠肝細(xì)胞內(nèi)粗面內(nèi)質(zhì)網(wǎng)排列整齊,核糖體較多且分布均勻。線粒體結(jié)構(gòu)完整。結(jié)論1.黃芪多糖可有效降低2型糖尿病大鼠血糖水平,改善其胰島素抵抗?fàn)顟B(tài)。2.黃芪多糖可降低TC、TG水平,改善2型糖尿病大鼠脂肪代謝紊亂狀態(tài)。3.APS可增加肝細(xì)胞抗氧化酶的活性,促進(jìn)氧自由基的清除,減少肝細(xì)胞損傷。4.黃芪多糖可減輕肝臟、腎臟組織損傷,改善肝、腎組織細(xì)胞形態(tài)和功能,降低尿微量白蛋白濃度,進(jìn)而改善肝、腎功能。
[Abstract]:The background of hypoinsulinism or (and) insulin resistance caused by a sustained high level blood glucose metabolic syndrome characterized. Sustained high levels of blood sugar can lead to a series of organ or tissue damage, such as fat metabolism, kidney, heart, eye, nerve function damage. Astragalus Polysaccharide (Astragalus polysaecharides, APS), the present study finds that it has anti-aging, enhance immunity, prevent lipid peroxidation and improve renal function. The effect of APS on the regulation of blood glucose levels in diabetic rats, improve blood lipid and renal function, and analyze the clinical value of APS in the treatment of diabetes by intraperitoneal injection. 40 mg/kg streptozotocin (Streptozotocin, STZ) and high fat diet, type 2 diabetic rat model was established. Close observation of type 2 diabetes mellitus treated with the intervention The blood glucose level, blood lipid level and liver kidney index changes, to further explore the clinical value of Astragalus Polysaccharide in the treatment and prevention of diabetes complications. Methods 6 week old Wistar rats in good health were 90, male, weight was 180 + 15g, were provided by the Xinxiang Medical University medical experimental animal center of the same. Under the environment of the breeding, free light, adequate intake of each diet, no significant difference. The room temperature was maintained at 23 - 2 DEG C, humidity is maintained at the beginning of 41% + 15%. before the experiment, 60 rats were randomly selected and divided into B group and C group, B group and C group rats were fed with high fat high sugar diet for 6 weeks, after intraperitoneal injection of streptozotocin. Type 2 diabetic rat model was established by intraperitoneal injection of 40 mg/kg STZ and high fat and high sugar feeding method, the modeling process, the rats in group T2DM (8/60), 13.3% animal deaths 52 survival 4 rats in blood glucose is not up, to be removed, and finally die. Only 48 were randomly divided into model control group (B group) and APS group (group C); more than 30 of 24 rats were randomly selected as normal control group (group A).C rats were given intragastric administration of APS 400 mg/kg/d, A, C group were given normal saline respectively. In the experiment of 0,2,4,6 weeks respectively were random samples of 6 rats were collected 24 hours urine metabolic cage method; fasting for 12 hours, the morning from tail vein blood glucose value is greater than or equal to 16.7mmol/l saidmodeling success. Then given the same diet, in after eating 0.5,1.0,1.5 and again 2 hours respectively to detect blood glucose levels. In vivo heart blood 5ml, serum preparation, detection of TC, TG, alt, AST, SOD and MDA respectively. The other level of liver, kidney, preparation of paraffin sections and electron microscopy, staining. The experimental data were analyzed by spss19.0 software, 姣旇緝3緇勫疄楠屽姩鐗╀笉鍚屾椂闂寸偣鍚勬寚鏍囧樊寮，

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