JPH09201145A - Animal model for renal osteodystrophy - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an animal model for a renal osteodystrophy by administering adenine, capable of simply and easily producing, and suitable for confirming a therapeutic effect on the renal osteodystrophy. SOLUTION: This animal model for a renal osteodystrophy is obtained by e.g. orally administering a feed containing approximately 0.75wt.% adenine of an animal origin, etc., for one month or more to a rat aging 4-10 weeks. Also, since the number of survival days of the model rat for the renal osteodystrophy is prolonged by administering the adenine by changing its amount to such as 0.50 or 0.25wt.% after administering the feed containing 0.75wt.% adenine for one month, it is preferable to decide a dose in accordance with the purpose and period of the test.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a model animal of renal osteodystrophy.

[0002]

2. Description of the Related Art The kidney is an organ that excretes blood components unnecessary for the living body and reabsorbs necessary substances to maintain homeostasis of the internal environment of living cells. When the function of the kidney is deteriorated and, for example, chronic renal failure occurs, unnecessary components in the body are excessively accumulated in the blood, and thus "maintenance dialysis therapy" is performed to remove such components from the blood. However, since the phosphorus cannot be completely removed even by dialysis, the phosphorus concentration in the blood rises, the balance with the calcium concentration in the blood is lost, and chronic hypocalcemia occurs. Then, excessive parathyroid hormone is secreted (secondary hyperparathyroidism), which melts bones and raises calcium concentration in blood, and as a result of continuing this state, bones become fragile and It becomes "nutrition". This has become a problem in recent years, and researches on therapeutic methods, therapeutic agents, therapeutic diets, etc. are underway.

Conventionally, model animals have been used for such research. Renal osteodystrophy model animal, by removing most of the kidney by surgery to create a state in which the function of the kidney is forcibly reduced, first as a chronic renal failure model animal, by continuing to breed further, It was designated as a "renal osteodystrophy model animal" with weakened bones. Further, continuous administration of adenine has also been studied as a model animal for chronic renal failure.

[0004]

However, it has been extremely time-consuming to operate one animal at a time, and it has been discovered that even if adenine is continuously administered, it can be applied to a model animal of renal osteodystrophy. There wasn't. Therefore, the present invention has been made for the purpose of providing a renal osteodystrophy model animal which can be simply and easily prepared and whose therapeutic effect on renal osteodystrophy can be confirmed.

[0005]

Means for Solving the Problems The present inventor has made various studies to solve the above-mentioned problems, and as a result, has arrived at the present invention. That is, the renal osteodystrophy model animal of the present invention is obtained by administering adenine.

[0006]

Embodiments of the present invention will be described below in detail. In the present invention, "%" means "% by weight". First, the model animals in the present invention are those usually used as model animals, and examples thereof include rats, mice, guinea pigs, hamsters, rabbits, dogs and monkeys.

In the present invention, adenine is a kind of purine base. Nucleic acid, ATP, NAD, FAD, CoA
Constituent components of coenzymes such as those mentioned above include those derived from animals and those derived from tea leaves, and animals and plants containing them are conceivable, but reagents that are usually easily available are acceptable.

Administration of adenine means oral administration,
Although intraperitoneal administration, intravenous administration and the like can be mentioned, oral administration is preferable because it is simple and easy. The amount of adenine varies depending on the species and age of the model animal, but in the case of rat, for example, it is advisable to administer a feed containing 0.75% adenine for one month or more. Moreover, after the feed containing adenine of about 0.75% was administered for one month, the amount of adenine was adjusted to 0.
If the dose is changed to 50% or 0.25%, the survival days of renal osteodystrophy model rats will be extended, so it is advisable to determine the dose according to the purpose and period of the test using model rats.

Next, a typical production method of the present invention will be described by taking an example of oral administration to a rat, which is easily available. First, prepare a rat. Although its species and age are not particularly limited, those of about 4 to 10 weeks are preferable in consideration of being used as a model animal in various experiments. Next, a feed containing adenine is prepared, and adenine may be mixed with the feed normally used for raising rats. This diet containing adenine is administered to rats. Administration may be carried out according to a conventional method. When a diet containing adenine is administered for one month in this manner, it becomes a renal osteodystrophy model rat.

In the case of intraperitoneal administration or intravenous administration, it is advisable to dissolve adenine in physiological saline or the like and periodically administer it.

[0011]

【Example】

Example 1 Six Wistar male rats (4 weeks old) were prepared, and the feed and water adjusted by the formulation (%) shown in Table 1 were freely taken. As adenine, "Adenine (special grade)" manufactured by Wako Pure Chemical Industries, Ltd. was used.

One month later, the rat was sacrificed and PTH in the blood was
The values of -C, phosphorus, creatinine, and active vitamin D were measured, and the bone density, body weight, and kidney weight were also measured. Compared to normal rats,
Since PTH-C, phosphorus, creatinine, kidney / body weight increased, and bone density and active vitamin D decreased, this rat can be said to have renal osteodystrophy.

[0013]

[Table 1]

[0014]

[Table 2]

Note 1) The values in parentheses in the table are the values measured in rats to which normal diet was administered.

Note 2) PTH-C The C-terminal of parathyroid hormone in blood was measured by immunoradiometry (pg / ml). Parathyroid hormone is a hormone that promotes bone resorption, and it can be seen that the higher the number, the more it tries to dissolve bone.

Note 3) Bone density: Dual energy X-ray absorption method for dual energy
The bone mineral content was measured by y X-ray absorptiometry and divided by the area (g / cm ² ). It can be seen that the smaller the value, the weaker the bone.

Note 4) Kidney weight / body weight Kidney weight / body weight × 100 (%) It can be seen that the larger the value, the larger the kidney.

Note 5) Phosphorus Phosphorus in blood was measured by the oxygen method (g / 100 ml). Since phosphorus increases due to renal failure, it can be seen that the higher the number, the lower the kidney function.

Note 6) Creatinine Creatinine in blood was measured by the Jaffe method (g /
100 ml). Creatinine is usually used as an index of kidney function, and it can be seen that the larger the number, the lower the kidney function.

Note 7) Activated vitamin D Blood 1α, 25 (OH) ₂ vitamin D was measured with a simple column (pg / ml). It has been known that 1α, 25 (OH) ₂ vitamin D is involved in calcium absorption and is markedly reduced in renal osteodystrophy.

[0022]

[Test example]

Test Example 1 Test Method 54 Wistar male rats (4 weeks old) were prepared, divided into 3 groups, and allowed to freely take the feed and water having the composition (%) shown in Table 3. 6 after 1 month, 2 months and 3 months
The animals were sacrificed one by one, and blood PTH-C, phosphorus, creatinine, active vitamin D, and bone density, body weight, and kidney weight were measured.

[0023]

[Table 3]

Test results are shown in Table 4. That is, from the table, renal osteodystrophy model animal of the present invention has reduced renal function, and,
It can be understood that the bone is weakened and the patient has renal osteodystrophy. Moreover, by returning to the normal diet after the administration of the adenine diet for 1 month, the respective values approached the values of the rats that continued to administer the normal diet, so the function of the renal osteodystrophy model animal was restored. It can be understood that it is suitable for research on therapeutic methods, therapeutic agents, therapeutic diets, etc.

[0025]

[Table 4]

Note 1) Adenine + normal diet After administering an adenine diet for 1 month, a regular diet was administered.

Note 2) The rats in the group to which the adenine diet was administered for 3 months had a low blood volume and could not measure active vitamin D.

Test Example 2 Test Method 18 renal osteodystrophy model rats obtained in the same manner as in Example 1 were divided into 3 groups, each having 6 rats except that the administration period of the feed was 40 days. Formulation (%) shown in Table 5, respectively
Were allowed free access to food and water, and sacrificed 20 days later, the effects of calcium carbonate and eggshell calcium on renal osteodystrophy were compared.

[0029]

[Table 5]

Test results are shown in Table 6. That is, it can be understood from the table that there is a clear difference between calcium carbonate and egg shell calcium, and that the renal osteodystrophy model animal of the present invention can confirm the therapeutic effect on renal osteodystrophy.

[0031]

[Table 6]

Note 1) PTH-N The N terminal of parathyroid hormone in blood was measured by immunoradiometry (pg / ml). Parathyroid hormone is a hormone that promotes bone resorption, and it can be seen that the higher the number, the more it tries to dissolve bone.

[0033]

Industrial Applicability As described above, the animal model for renal osteodystrophy of the present invention can be simply and easily prepared and the therapeutic effect on renal osteodystrophy can be confirmed.

Claims (1)

[Claims] 1. A renal osteodystrophy model animal obtained by administration of adenine.