A Rat Model of Adenine-induced Chronic Renal Failure Complicated with Cardiovascular Disease / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo 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. MethodRats 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. Result① Compared with the normal group， the model group showed a significant decrease in body weight （P<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 （P<0.05）， which increased gradually over time. At week 17， uric acid levels were significantly elevated （P<0.05）， and blood calcium levels were reduced at the end of week 17 （P<0.01）. ④ Compared with the normal group， the model group showed a significant increase in blood pressure at week 5 （P<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 （P<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. ConclusionAdenine by gavage at 150 mg·kg-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.