四氧嘧啶诱导犬1型糖尿病病理模型建立及其毒副作用研究

发布时间：2018-03-18 18:50

  本文选题：犬　切入点：糖尿病　出处：《华中农业大学》2008年硕士论文　论文类型：学位论文

【摘要】： 目前犬糖尿病的发生率越来越高,有报道其发病率为1:100-500,几乎所有的犬糖尿病都是1型糖尿病,但是目前对犬1型糖尿病模型的制作方法还不成熟,并且相关报道非常少,阻碍了对犬糖尿病的进一步研究。传统上诱导糖尿病模型的药物有四氧嘧啶和链脲霉素,但是链脲霉素价格昂贵;用四氧嘧啶诱导犬1型糖尿病,价格相对要便宜很多,成模率高。本实验研究四氧嘧啶诱导犬1型糖尿病模型,摸索其造模方法,观察四氧嘧啶对肝脏,肾脏和胰腺的影响,并为以后的犬1型糖尿病造模提供新的方法和理论依据。 1.犬1型糖尿病模型的建立 实验犬禁食12h,四氧嘧啶按30mg/kg的剂量静脉推注,推注时间在30s内完成),注射后连续测定血糖,每2h测定一次,直到血糖值稳定。之后,再按30mg/kg的剂量静脉注射一次,每2h测定一次血糖值直至稳定。若中间测定血糖值过低,则静脉注射10%的葡萄糖解救;若出现血糖值过高的情况,则用1U/kg胰岛素剂量治疗。3天后让犬自由饮食,晚上8时给实验犬饲喂成犬粮,次日上午8时静脉采血0.5mL测血糖值。观察犬的精神状况、饮食情况和尿量变化。给药后每周测一次血糖,做好记录。1型糖尿病模型的判定标准是连续2天空腹血糖值超过11.1mmol%qL。 2.四氧嘧啶对犬肝脏,肾脏和胰腺的毒副作用的研究 测定用药前后肝功能指标(ALT、AST、ALP和CHE),肾功能指标(CRE和UREA),胰腺功能相关指标(AMY)的变化,并且对相关组织做组织病理学检查,结合血清学生化指标进行综合分析,得出最后结果。 3.结果 实验犬经过四氧嘧啶以30mg/kg的剂量2次给药后,血糖最终稳定在20mmol%qL左右。一只犬死亡,其它犬出现典型的1型糖尿病症状,表现为多饮、多尿、多食、烦渴、消瘦等症状。以上结果表明,本试验成功地完成了犬1型糖尿病建模。 组织病理学变化:肝脏细胞肿大、破裂,胞浆外逸,颗粒变性和空泡变性,有广泛的碎屑状坏死,细胞核浓缩与碎裂;从切片中未见有明显的肾脏病变,肾组织结构正常;胰腺的腺泡破裂,或者界限不清,众多腺泡融合成一个大腺泡,少见胰岛和B细胞。 血清学指标变化:经过四氧嘧啶2次30mg/kg剂量给药后,四氧嘧啶对肝脏的功能有明显的影响,碱性磷酸酶(ALP)从第一周到第六周与给药前相比明显升高,差异性极显著(P＜0.01),丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和胆碱酯酶(CHE)前三周与给药前相比无明显变化,差异性不显著(P＞0.05),但是从第四周开始与给药前相比开始明显升高,差异性极显著(P＜0.01);四氧嘧啶给药后对肾功能影响不大,血清肌酐(CRE)和尿素(UREA)与给药前无明显变化,差异性不显著(P＞0.05);四氧嘧啶给药后对胰腺的功能有明显的影响,血清淀粉酶(AMY)从第一周到第六周与给药前相比较均有极明显的升高,差异性极显著(P＜0.01)。 4.结论 四氧嘧啶30mg/kg的剂量2次给药成功地诱导了犬1型糖尿病模型,空腹血糖值稳定在20mmol/L左右,达到1型糖尿病模型的标准,模型稳定,成模率高。四氧嘧啶对肝脏和胰脏功能有严重的影响并且造成了器质性损伤,但对肾脏功能无明显的影响,模型犬的成活率比较高。本实验利用四氧嘧啶小剂量多次给药诱导犬1型糖尿病模型,对以后的犬1型糖尿病模型的诱导提供了新的方法和理论依据。
[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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