RU2369391C1 - Method of osteoporosis correction and prevention of osteoporotic fractures by means of losartan - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: to correct osteoporosis and prevent osteoporotic fractures osteoporosis in female Wistar rats is simulated by means of bilateral ovariotomy. Then the said rats are intragastically fed with losartan of 6 mg/kg once a day every day within 8 weeks after ovariotomy. Osteoprotective losartan action is estimated with respect to microcirculation in bone tissue and width of trabecula of bone.

EFFECT: prevention of osteoparotic fractures after ovariotomy by blocking Angiotensin II Receptor, improved intraosseous microcirculation.

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Description

The invention relates to medicine, in particular to experimental pharmacology, and for the correction of osteoporosis.

Closest to the claimed solution is a method for the prevention of osteoporosis in patients with chronic coronary heart disease (CHD) using the drug Calcium-D3 (Bazhenov A.N., Koltsova I.V., Yaroshenko G.A., patent application No. 2005124634/14 from 02.08.2005), which consists in the fact that, in addition to the generally accepted anti-ischemic and antithrombotic therapy of HIBS, the drug Calcium-D3 is administered by adjusting the dose, the frequency of administration and the duration of the course of treatment depending on the functional class of angina pectoris, age and gender of the patient.

The main disadvantage of this method is that Calcium-D3 is considered as an anti-osteoporotic drug and the anti-osteoporotic effect of AT1 receptor blockers, in particular losartan, is not evaluated, and data on the degree of improvement of blood supply to bone tissue with losartan are not presented.

The technical result of the invention is a method for the correction of osteoporosis and prevention of osteoporotic fractures, including the use of losartan.

The technical result is achieved by the fact that, against the background of modeling osteoporosis in an experiment using bilateral ovariectomy in a laboratory animal, it is corrected for 8 weeks by daily, once daily, intragastric administration of losartan at a dose of 6 mg / kg, which, by blocking angiotensin II receptors, prevents the development of its effects and thereby reduces arterial vasoconstriction and leads to peripheral vasodilation.

The method is carried out as follows.

The experiments were performed on rats of Wistar female females weighing 200-250 g. Ovariectomy was performed under anesthesia - chloral hydrate intraperitoneally at a dose of 300 mg / kg at the rate of 0.1 ml of solution per 100 g of animal weight. On day 57 (after 8 weeks) from the start of the experiment under anesthesia (chloral hydrate intraperitoneally at a dose of 300 mg / kg), microcirculation was measured in the proximal metaphysis of the right thigh. Microcirculation level was measured using Biopac systems equipment: MP100 polygraph with LDF100C laser Doppler flowmetry module and TSD144 invasive sensor, and AcqKnowledge software version 3.8.1. After measuring microcirculation, the femurs were taken for histological examination; histological preparations of proximal femur metaphyses were stained with hematoxylin and eosin. Optical microscopy of the preparations was carried out using a Leica CME microscope (magnification × 100) with photographing of the preparations using an Olympus SP-350 camera (resolution 3264 × 2448). A morphometric study of the obtained photographs was performed using the ImageJ program version 1.39, during which the width of the bone trabeculae was estimated.

When statistical data processing was calculated, the average value, the standard error. Differences were considered significant at p <0.05.

EXAMPLE OF SPECIFIC PERFORMANCE

The average level of microcirculation in the proximal hip metaphysis in intact animals was 100.5 ± 4.4 perfusion units (PE); the average width of the bone trabeculae was 97.7 ± 1.0 μm (Table 1).

Bilateral ovariectomy 8 weeks after the start of the experiment in experimental animals led to a significant decrease in the average level of microcirculation compared with intact animals to a value of 61.5 ± 3.7 PE. There were signs of osteoporosis: the average width of the bone trabeculae was 61.7 ± 1.2 μm (Table 1). The discovered fact of a decrease in blood supply to bone tissue is an additional factor in the development of osteoporosis in the hypoestrogenic state, leading to osteoporotic fractures.

In the group of animals that received intragastric losartan at a dose of 6 mg / kg daily for 8 weeks after ovariectomy, there was a significant increase in the average level of microcirculation in the proximal hip metaphysis compared to the experimental group to 100.0 ± 2.3 PE. At the same time, a significant increase in the average width of the bone trabeculae was observed compared with the animals of the experimental group to 84.8 ± 0.6 μm (Table 1).

Table 1. The dynamics of the average level of microcirculation in the proximal metaphysis of the thigh and the average width of the bone trabeculae in the modeling of osteoporosis and its correction with losartan Groups of animals The level of microcirculation, PE The width of the bone trabecula, microns Intact 100.5 ± 4.4 97.7 ± 1.0 Non-received treatments (experimental) 61.5 ± 3.7 * 61.7 ± 1.2 * Received for 8 weeks, losartan at a dose of 6 mg / kg 100.0 ± 2.3 ** 84.8 ± 0.6 ** * - p <0.05 compared with the group of intact animals ** - p <0.05 compared with a group of experimental animals

Thus, losartan against the background of bilateral ovariectomy increases the level of microcirculation in the proximal hip metaphysis to the level of intact animals and, due to increased blood supply to the bone tissue, slows down the development of osteoporosis in the hypoestrogenic state, which, in turn, reduces the likelihood of osteoporotic fractures.

Claims (1)

A method for correcting osteoporosis and preventing the occurrence of osteoporotic fractures, characterized in that against the background of modeling osteoporosis in an experiment using bilateral ovariectomy, female Wistar rats are administered intragastrically losartan at a dose of 6 mg / kg daily once a day for 8 weeks after ovariectomy, evaluating the osteoprotective effect losartan according to the level of microcirculation in the bone tissue and the width of the bone trabeculae.