慢性肾衰动物模型制备方法及大黄游离蒽醌的药效学研究

发布时间：2017-12-31 09:25

本文关键词：慢性肾衰动物模型制备方法及大黄游离蒽醌的药效学研究　出处：《成都中医药大学》2007年硕士论文　论文类型：学位论文

【摘要】： 目的:比较3/4肾切除、5/6肾切除、腺嘌呤灌胃、单侧肾上、下极结扎、单侧肾上、下极结扎并外侧冷冻5种慢性肾功能衰竭(CRF)模型的稳定性,初步探讨大黄游离蒽醌对CRF的药效作用。方法:SD大鼠随机分为正常组和模型Ⅰ(腺嘌呤)组,模型Ⅱ(3/4肾切除)组,模型Ⅲ(5/6肾切除)组,模型Ⅳ(单侧肾上、下极结扎)组,模型Ⅴ(单侧肾上、下极结扎并外侧冷冻)组。造模4周、8周后,观察大鼠一般状况、体重变化、大鼠死亡情况、血清尿素氮(BUN)、肌酐(Cr)变化。选择5/6肾切除模型,给予不同剂量大黄游离蒽醌灌胃,观察大鼠一般情况、体重改变、血清BUN、Cr变化以及残肾的病理改变。结果:1.各模型组大鼠体重比较正常组明显下降(p＜0.05);2.造模4周、8周后,各模型组大鼠血清BUN、Cr水平明显高于正常组(p＜0.01);3.造模4周一8周,模型Ⅲ组比较模型Ⅰ、Ⅱ、Ⅳ、Ⅴ组大鼠死亡率明显降低;4.大黄游离蒽醌灌胃给药4周后,大、小剂量治疗组大鼠血清BUN、Cr较模型对照组明显降低(p＜0.01或0.05);残肾肾小管以及肾小球数量比较模型对照组明显增加(p＜0.05);残肾肾小球平均面积、周长、最大直径、最小直径明显小于模型对照组(p＜0.01或0.05),肾小球基底膜(GBM)以及系膜平均面积、积分光密度值较模型对照组明显减小(p＜0.05)。结论:与其他4种CRF造模方法比较,5/6肾切除是一种比较稳定而且理想的CRF动物模型。大黄游离蒽醌能有效降低CRF大鼠血清BUN、Cr水平,抑制残余肾组织的纤维化和代偿性增生和肥大,改善肾小管硬化程度,抑制系膜细胞增生和细胞外基质的积聚,延缓大鼠慢性肾功能衰竭的进程。
[Abstract]:Objective: To compare the stability of 5 chronic renal failure (CRF) models, including 3/4 nephrectomy, 5/6 nephrectomy, adenosine perfusion, unilateral upper and lower pole ligation, unilateral suprarenal ligation and lateral ligation, and preliminarily investigate the effect of rhubarb free anthraquinone on CRF.
Methods: SD rats were randomly divided into normal group and model group (Xian Piaoling), model II (3/4 nephrectomy group), model III (5/6 nephrectomy group), model IV (unilateral kidney, lower pole ligation group (V) model of unilateral kidney, lower pole ligation and lateral freezing group) at 4 weeks, 8 weeks later, observe the general condition of rats, body weight changes, the rats death, serum urea nitrogen (BUN), creatinine (Cr) changes. Select the 5/6 nephrectomy model, given different doses of rhubarb free anthraquinones by gavage, the general condition of rats was observed, the change of body weight, serum BUN. Change the Cr and pathological changes of remnant kidney.
Results: 1. the body weight of rats in the model group compared with normal group decreased significantly (P < 0.05); 2., 4 weeks, 8 weeks later, the rats in the model group serum BUN, Cr levels were significantly higher than the normal group (P < 0.01); 3. model 4 Monday of the 8 week, compared with model group model II, IV, V, mortality group rats decreased significantly; 4. free anthraquinone by gavage for 4 weeks, and treated with small dose of serum of rats in the BUN group, Cr was significantly lower than the model control group (P < 0.01 or 0.05); the number of residual renal tubular and glomerular compared with model control group was significantly increased (P < 0.05); the average area of residual renal glomerular perimeter, maximum diameter, minimum diameter was significantly less than the model control group (P < 0.01 or 0.05), glomerular basement membrane (GBM) and the average mesangial area, integral optical density than the model control group decreased significantly (P < 0.05).
Conclusion: compared with other 4 kinds of modeling methods of CRF, 5/6 nephrectomy is a relatively stable and ideal animal model of CRF. The free anthraquinone can effectively reduce serum BUN, CRF level of Cr rats, inhibit the residual kidney fibrosis and compensatory hyperplasia and hypertrophy of renal tubular atherosclerosis, inhibit the proliferation of cell membrane and extracellular matrix accumulation, delaying chronic renal failure in rats.

【学位授予单位】：成都中医药大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R-332;R285.5

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