本文選題：犬　切入點：糖尿病　出處：《華中農(nóng)業(yè)大學》2008年碩士論文　論文類型：學位論文

【摘要】： 目前犬糖尿病的發(fā)生率越來越高,有報道其發(fā)病率為1:100-500,幾乎所有的犬糖尿病都是1型糖尿病,但是目前對犬1型糖尿病模型的制作方法還不成熟,并且相關報道非常少,阻礙了對犬糖尿病的進一步研究。傳統(tǒng)上誘導糖尿病模型的藥物有四氧嘧啶和鏈脲霉素,但是鏈脲霉素價格昂貴;用四氧嘧啶誘導犬1型糖尿病,價格相對要便宜很多,成模率高。本實驗研究四氧嘧啶誘導犬1型糖尿病模型,摸索其造模方法,觀察四氧嘧啶對肝臟,腎臟和胰腺的影響,并為以后的犬1型糖尿病造模提供新的方法和理論依據(jù)。 1.犬1型糖尿病模型的建立 實驗犬禁食12h,四氧嘧啶按30mg/kg的劑量靜脈推注,推注時間在30s內(nèi)完成),注射后連續(xù)測定血糖,每2h測定一次,直到血糖值穩(wěn)定。之后,再按30mg/kg的劑量靜脈注射一次,每2h測定一次血糖值直至穩(wěn)定。若中間測定血糖值過低,則靜脈注射10%的葡萄糖解救;若出現(xiàn)血糖值過高的情況,則用1U/kg胰島素劑量治療。3天后讓犬自由飲食,晚上8時給實驗犬飼喂成犬糧,次日上午8時靜脈采血0.5mL測血糖值。觀察犬的精神狀況、飲食情況和尿量變化。給藥后每周測一次血糖,做好記錄。1型糖尿病模型的判定標準是連續(xù)2天空腹血糖值超過11.1mmol%qL。 2.四氧嘧啶對犬肝臟,腎臟和胰腺的毒副作用的研究 測定用藥前后肝功能指標(ALT、AST、ALP和CHE),腎功能指標(CRE和UREA),胰腺功能相關指標(AMY)的變化,并且對相關組織做組織病理學檢查,結(jié)合血清學生化指標進行綜合分析,得出最后結(jié)果。 3.結(jié)果 實驗犬經(jīng)過四氧嘧啶以30mg/kg的劑量2次給藥后,血糖最終穩(wěn)定在20mmol%qL左右。一只犬死亡,其它犬出現(xiàn)典型的1型糖尿病癥狀,表現(xiàn)為多飲、多尿、多食、煩渴、消瘦等癥狀。以上結(jié)果表明,本試驗成功地完成了犬1型糖尿病建模。 組織病理學變化:肝臟細胞腫大、破裂,胞漿外逸,顆粒變性和空泡變性,有廣泛的碎屑狀壞死,細胞核濃縮與碎裂;從切片中未見有明顯的腎臟病變,腎組織結(jié)構(gòu)正常;胰腺的腺泡破裂,或者界限不清,眾多腺泡融合成一個大腺泡,少見胰島和B細胞。 血清學指標變化:經(jīng)過四氧嘧啶2次30mg/kg劑量給藥后,四氧嘧啶對肝臟的功能有明顯的影響,堿性磷酸酶(ALP)從第一周到第六周與給藥前相比明顯升高,差異性極顯著(P＜0.01),丙氨酸氨基轉(zhuǎn)移酶(ALT)、天門冬氨酸氨基轉(zhuǎn)移酶(AST)和膽堿酯酶(CHE)前三周與給藥前相比無明顯變化,差異性不顯著(P＞0.05),但是從第四周開始與給藥前相比開始明顯升高,差異性極顯著(P＜0.01);四氧嘧啶給藥后對腎功能影響不大,血清肌酐(CRE)和尿素(UREA)與給藥前無明顯變化,差異性不顯著(P＞0.05);四氧嘧啶給藥后對胰腺的功能有明顯的影響,血清淀粉酶(AMY)從第一周到第六周與給藥前相比較均有極明顯的升高,差異性極顯著(P＜0.01)。 4.結(jié)論 四氧嘧啶30mg/kg的劑量2次給藥成功地誘導了犬1型糖尿病模型,空腹血糖值穩(wěn)定在20mmol/L左右,達到1型糖尿病模型的標準,模型穩(wěn)定,成模率高。四氧嘧啶對肝臟和胰臟功能有嚴重的影響并且造成了器質(zhì)性損傷,但對腎臟功能無明顯的影響,模型犬的成活率比較高。本實驗利用四氧嘧啶小劑量多次給藥誘導犬1型糖尿病模型,對以后的犬1型糖尿病模型的誘導提供了新的方法和理論依據(jù)。
[Abstract]:The dogs in the incidence of diabetes is higher and higher, the reported incidence rate of 1:100-500, almost all of the canine diabetes is type 1 diabetes, but the current production method of canine model of type 1 diabetes is still not mature, and the relevant reports are very few, hinder the further research on canine diabetes. Traditional induced diabetic model the drug has four alloxan and streptozotocin streptozotocin, but the price is expensive; four alloxan induced canine type 1 diabetes, the price is relatively cheaper, a high successful rate. The experimental study of four alloxan to induce type 1 diabetes model dogs, explore the method, observation of four oxygen pyrimidine the effect of liver, kidney and pancreas, and for the future of the canine type 1 diabetes model to provide new methods and theoretical basis.
Establishment of a model of type 1 diabetes in 1. dogs
Dogs fasted for 12h, four oxygen pyrimidine by 30mg/kg dose intravenous injection, injection time within 30s after injection), continuous blood glucose determination, 2h determination of each time, until the stable blood glucose level. Then, according to the dose of intravenous injection of 30mg/kg once every 2h a blood glucose determination until stable if the middle blood glucose value is too low, the intravenous 10% glucose free; if the blood sugar is too high, the use of 1U/kg insulin doses after.3 days of treatment for the dog free diet, 8 pm to feeding dogs into dog food, the next morning when 8 0.5mL of venous blood glucose values measured. To observe the canine mental state change, diet and urine volume. After administration of a blood glucose was measured every week, standard record of type.1 diabetes model is 2 consecutive daysfasting glucose value more than 11.1mmol%qL.
2. study on the toxic and side effects of pyrimidine on the liver, kidney and pancreas of dogs
The changes of liver function indexes (ALT, AST, ALP and CHE), renal function indexes (CRE and UREA) and pancreatic function related indexes (AMY) before and after treatment were determined. The histopathological examination of related tissues and comprehensive analysis of serological and biochemical indexes were carried out to get the final results.
3. results
Dogs after four alloxan at a dose of 30mg/kg after the 2 dose, blood sugar stable at about 20mmol%qL finally. The dog died, other dogs showed typical symptoms of type 1 diabetes, such as polydipsia, polyuria, polyphagia, polydipsia, weight loss and other symptoms. The above results show that the test successfully the dog model of type 1 diabetes.
Histopathological changes of liver cell swelling, rupture, cytoplasm escape, granular degeneration and vacuolar degeneration, extensive piecemeal necrosis, nucleus pyknosis and cataclasm; no from sections have obvious renal lesions, normal renal tissue structure; pancreatic acinar rupture, or is unclear, many acini merge into a a rare acinar, islets and B cells.
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本文編號：1630858