A Rat Model of Adenine-induced Chronic Renal Failure Complicated with Cardiovascular Disease

ZHANG Yuanyuan; JIN Peipei; LI Wanzhe; GUO Dengzhou

doi:10.13422/j.cnki.syfjx.20230612

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A Rat Model of Adenine-induced Chronic Renal Failure Complicated with Cardiovascular Disease

更新时间：2023-07-18

- A Rat Model of Adenine-induced Chronic Renal Failure Complicated with Cardiovascular Disease
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 16, Pages: 79-88(2023)
- 作者机构：
  
  1.河北中医药大学研究生学院，石家庄 050200
  2.河北中医药大学第一附属医院/河北省中医院，石家庄 050011
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230612
  CLC： R284;R285;R289;R287;R22;R2-031;R33;R24
- Published：20 August 2023，
  
  Published Online：28 April 2023，
  
  Received：21 March 2023，
- 稿件说明：
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张圆圆,靳培培,李宛哲等.腺嘌呤诱导慢性肾功能衰竭并发心血管病变大鼠模型的分析[J].中国实验方剂学杂志,2023,29(16):79-88.

ZHANG Yuanyuan,JIN Peipei,LI Wanzhe,et al.A Rat Model of Adenine-induced Chronic Renal Failure Complicated with Cardiovascular Disease[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(16):79-88.
张圆圆,靳培培,李宛哲等.腺嘌呤诱导慢性肾功能衰竭并发心血管病变大鼠模型的分析[J].中国实验方剂学杂志,2023,29(16):79-88. DOI： 10.13422/j.cnki.syfjx.20230612.

ZHANG Yuanyuan,JIN Peipei,LI Wanzhe,et al.A Rat Model of Adenine-induced Chronic Renal Failure Complicated with Cardiovascular Disease[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(16):79-88. DOI： 10.13422/j.cnki.syfjx.20230612.

摘要

目的

通过观察腺嘌呤灌胃不同时间对模型大鼠一般生命体征、生化指标、心肾组织结构及功能的影响，探讨腺嘌呤诱导慢性肾功能衰竭（CRF）并发心血管病变大鼠模型的制备方法。

方法

模型组大鼠腺嘌呤150 mg·kg

-1

·d

-1

灌胃16周，正常组大鼠给予等体积0.5%羧甲基纤维素钠溶液灌胃。于第5、13、17周检测模型组及正常组大鼠24 h尿蛋白定量（24 h-UTP）、生化指标、心脏超声，心肾组织结构及功能变化；于第5周、13周检测模型组及正常组大鼠血压；每周记录大鼠体质量变化；每日观察大鼠一般情况。

结果

①与正常组大鼠比较，模型组大鼠体质量明显减少（

0.05）；②与正常组大鼠比较，模型组大鼠尿量明显增多，13周时出现蛋白尿；③与正常组大鼠比较，模型组大鼠第5周开始甘油三酯（TG）、总胆固醇（TC）、肌酐（Cr）、尿素氮（BUN）、血钾、血磷差异具有统计学意义（

0.05），第17周时尿酸明显升高（

0.05）；血钙降低（

0.01）；④与正常组大鼠比较，模型组大鼠第5周出现血压明显升高（

0.05），并逐渐加重；⑤与正常组大鼠比较，模型组大鼠第5周左心室室壁厚度差异无统计学意义，第13周差异有统计学意义（

0.05）；⑥与正常组大鼠比较，模型组大鼠第5周肾脏出现纤维化，纤维化程度不断加重，第13周心血管周围出现明显纤维化；⑦与正常组大鼠比较，模型组大鼠近端小管上皮细胞内可见高密度菱形针状结晶不断增多，细胞膜完整性受损，细胞间距不断增加，溶酶体不断增多，线粒体增生、线粒体嵴和线粒体外膜致密变不断加重；⑧与正常组大鼠比较，模型组大鼠精神萎靡，活动量明显减少并蜷缩弓背，毛发枯燥，耳部及脚趾苍白，面颊肿胀，夜尿多，血液暗红且浓稠。

结论

腺嘌呤150 mg·kg

-1

·d

-1

灌胃12周可制备大鼠CRF伴有心血管病变等并发症模型，可用于CRF及其心血管病变等并发症的防治研究；腺嘌呤诱导CRF大鼠模型证属脾肾阳虚、浊瘀阻滞，可用于温补脾肾，化瘀泄浊的中药组方防治CRF进展机制的研究。

Abstract

Objective

To explore the preparation method of a rat model of adenine-induced chronic renal failure complicated with cardiovascular disease by investigating the effect of different time points of adenine gastric lavage on general vital signs， biochemical indicators， and cardiac and renal tissue structure and function of model rats.

Method

Rats in the model group were administered adenine at 150 mg·kg

-1

·d

-1

by gavage for 16 weeks， while those in the normal group were given an equal volume of 0.5% carboxymethyl cellulose sodium solution by gavage. At weeks 5， 13， 17， 24-hour urinary protein quantification （24 h-UTP）， biochemical indicators， cardiac ultrasound， and changes in cardiac and renal tissue structure and function were measured in both the model and normal groups. Blood pressure was measured at weeks 5 and 13 in both groups. Weekly changes in body weight were recorded， and general conditions of the rats were observed daily.

Result

① Compared with the normal group， the model group showed a significant decrease in body weight （

0.05）. ② Rats in the model group exhibited a significant increase in urine volume， and proteinuria appeared at week 13. ③ Compared with the normal group， the model group showed significant differences in triglyceride （TG）， total cholesterol （TC）， creatinine （Cr）， blood urea nitrogen （BUN）， blood potassium， and blood phosphorus at week 5 （

0.05）， which increased gradually over time. At week 17， uric acid levels were significantly elevated （

0.05）， and blood calcium levels were reduced at the end of week 17 （

0.01）. ④ Compared with the normal group， the model group showed a significant increase in blood pressure at week 5 （

0.05）， which progressively worsened. ⑤ There was no statistically significant difference in left ventricular wall thickness between the model and normal groups at week 5， but a significant difference was observed at week 13 （

0.05）. ⑥ Fibrosis appeared in the kidneys of rats in the model group at week 5 and gradually worsened， while obvious fibrosis occurred around the cardiovascular system at week 13 as compared with the results in the normal group. ⑦ In the proximal tubular epithelial cells of the model group， there was an increasing presence of high-density rhomboid needle-shaped crystals， damaged cell membrane integrity， increased cell spacing， increased lysosomes， increased mitochondrial proliferation， denser mitochondrial cristae， and outer mitochondrial membrane. ⑧ Compared with the rats in the normal group， rats in the model group exhibited depressed spirits， significantly reduced activity， hunched posture， dry fur， pale ears and toes， swollen cheeks， increased nocturnal urination， and dark and viscous blood.

Conclusion

Adenine by gavage at 150 mg

-1

·d

-1

for 12 weeks can be used to establish a rat model of chronic renal failure complicated with cardiovascular disease， which can be used for the prevention and treatment research on chronic renal failure and its associated cardiovascular complications. The syndrome of adenine-induced rat model of chronic renal failure belongs to the deficiency of spleen and kidney， turbidity and stasis obstruction， and can be used to study the mechanisms of warming and tonifying the spleen and kidney， resolving stasis， and eliminating turbidity in the treatment of chronic renal failure.

关键词

腺嘌呤CRF心血管损伤脾肾阳虚、浊瘀阻滞

Keywords

adeninechronic renal failurecardiovascular injurydeficiency of spleen and kidney， turbidity and stasis obstruction

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Related Institution

Affiliated Hospital of Hebei University of Chinese Medicine/Hebei Provincial Hospital of Traditional Chinese Medicine

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Shanxi University of Traditional Chinese Medicine

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