[Animal Modeling] - Adenine Method for Kidney Yang Deficiency Syndrome Animal Model

  (1) Reproduction method: Adult rats were fed with a feed containing 0.5% adenine, with a daily dose of approximately 350mg/kg body weight. Changes in animal weight, body temperature, urine volume, demeanor, body hair, and mobility were observed. On the 30th day of feeding, urine was collected to measure urinary osmotic pressure, blood was taken from the carotid artery to detect biochemical indicators such as testosterone (T), estradiol (F2), luteinizing hormone (LH), follicle stimulating hormone (FSH), chorionic gonadotropin (CG), triiodothyronine (T3), thyroxine (T4), cortisol (F), cAMP, and cGMP. Animals were sacrificed and their kidneys and testes were taken for histological and histochemical examination.

  (2) Model characteristics: Animals are becoming increasingly thin and begin to recover after 10 days, but their growth and development are far inferior to normal animals. Their body temperature decreases, leading to polyuria, uneven and sparse body hair, fear of cold, cold limbs, curling up and arching their backs, mental fatigue, slow response, less movement and eye closure, and pale tails. After being raised for more than 1 month, some animals may die due to muscle tremors, convulsions, and other failures; Animal kidney qi deficiency leads to polyuria, hypotonic urine, and a decrease in urea and creatinine excretion after 30 days; Impairment of sexual and reproductive functions, atrophy of the testes, degeneration and degeneration of most of the seminiferous tubules, thinning of the reproductive epithelium within the lumen, degeneration of various levels of sperm cells, significant reduction or absence of sperm production, increased connective tissue between the seminiferous tubules, and a significant decrease in the number of interstitial cells; The levels of T, E2, LH, and CG in plasma decreased, while T3, T4, and F showed a tendency to decrease. The cAMP content in plasma increases, while the cAMP content in renal tissue tends to increase. The naked eye observation of the kidney shows an increase in volume, swelling, and pale color, which is called a "large white kidney". Microscopically, the renal parenchyma shows degenerative changes, with a significant decrease in the number of renal corpuscles. Within the same field of view, there are only 3-4 renal corpuscles, and the renal balloon cavity expands. There are brown black 2,8 dihydroxyadenine crystal deposits in the renal tubules, especially in the lumen and interstitium of the proximal tubules. The epithelium of the proximal tubules with crystal deposits becomes thinner, and the lumen expands, There is interstitial hyperplasia of connective tissue such as shed epithelium and neutrophils in the cavity. The renal tubular PAS, alkaline phosphatase (AKP), glucose-6-phosphatase (G-6-P), glucose-6-phosphate dehydrogenase (G-6-PDH), citrate dehydrogenase (ICDH), L-malate dehydrogenase (L-MDH), and very specific enzyme (NSE) reactions in model animals were significantly weakened.

  (3) When the body ingests large doses of adenine in comparative medicine, abnormally high concentrations of adenine are converted into 2,8-dihydroxyadenine, which is extremely difficult to dissolve in water, under the action of xanthine oxidase. This adenine metabolite deposits in the renal tubules, causing renal failure. It is also found that adenine metabolites not only cause renal failure due to mechanical obstruction of the renal tubular surface, but may also be due to the "toxic" effect of adenine metabolites, Inhibiting the activity of various enzymes related to sugar, fat, and protein metabolism in kidney tissue may affect the energy metabolism of kidney tissue, which may be one of the mechanisms by which adenine causes "kidney yang deficiency" syndrome. In the field of traditional Chinese medicine, people consider