RU2432618C1 - Method for placental microcirculation disorder correction in adma-like gestosis models in experiment - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: methods for endothelial dysfunction correction are developed by simulating of an ADMA-like gestosis model in pregnant laboratory pregnant Wistar rats by intraperitoneal introduction of L-nitro-arginin methyl ester 25 mg/kg for 7 days. For endothelial dysfunction correction, such simulation is combined with intragastric introduction resveratrol 2 mg/kg once a day for 7 days. ^ EFFECT: method provides expressed placental microcirculation disorder correction in the condition of radical change of an endocrine profile and regulatory mechanism relationships during pregnancy due to an integrated effect of resveratrol exhibiting certain estrogenic activity and antioxidant properties. ^ 1 ex

Description

The invention relates to medicine, in particular to experimental pharmacology.

Closest to the claimed solution is a method for correcting microcirculation disorders in the placenta in pregnant animals using L-arginine, a substrate for the synthesis of nitric oxide. According to the description of experimental studies in the article: “Pharmacological correction by L-arginine of“ ADMA-eNOS-associated targets ”in experimental preeclampsia”, Kuban Scientific Medical Bulletin, No. 1, 2010, pp. 85-92.

The main disadvantage of this method is the lack of assessment of correction of microcirculation disorders in the placenta when modeling gestosis in pregnant female Wistar rats using resveratrol. One of the leading factors in the development of pathophysiological changes in the cardiovascular system during pregnancy and the development of gestosis is oxidative stress and a decrease in the activity of endothelial NO synthase (e-NOS). The result is a manifestation of endothelial dysfunction in pregnant women, which leads to a violation of microcirculation in the placenta. Therefore, the results of the correction of microcirculation disorders in an ADMA-like model of pathology in pregnant animals using L-arginine are unsatisfactory.

The objective of the invention is a method for correcting microcirculation disorders in an ADMA-like model of pathology in pregnant animals, including the use of resveratrol related to antioxidants, activators of NO synthase.

The task is achieved by the fact that against the background of gestosis simulation in an experiment, an intraperitoneal administration of pregnant female Wistar rats for 7 days to an ADMA-like blocker of endothelial NO synthase-N-nitro-L-arginine-methyl ether (L-NAME) at a dose of 25 mg / kg microcirculatory disorders are corrected by intragastric administration of resveratrol at a dose of 2 mg / kg once a day. This leads to a pronounced correction of microcirculation disorders in the placenta, since the administration of resveratrol leads to an endothelioprotective effect associated with the prevention of uncoupling of endothelial NO synthase and an increase in its activity.

The method is carried out as follows.

The experiments were carried out on white pregnant rats-female Wistar line weighing 250-300 g with a gestation period of 14 days. N-nitro-L-arginine methyl ether (L-NAME) is administered intraperitoneally at a dose of 25 mg / kg / day for 7 days. Resveratrol is administered intragastrically at a dose of 2 mg / kg / day for 7 days. On day 8 from the start of the experiment (21-22 days of pregnancy), microcirculation in the placenta was measured under anesthesia. The placenta microcirculation was studied using Biopac systems equipment: MP100 polygraph with laser Doppler flowmetry (LDF) LDf100C module and TSD144 sensor. The LDF results were recorded using the Acqknowledge version 3.8.1 program; microcirculation values were expressed in perfusion units (PE).

In statistical data processing, the average value of the standard deviation is calculated. Differences are considered significant at p <0.05.

EXAMPLE OF SPECIFIC PERFORMANCE

Blockade of NO synthase caused by a 7-day administration of L-NAME to pregnant rats led to impaired microcirculation in the placenta, as evidenced by a decrease in its value from 425.90 ± 39.55 PE in intact pregnant animals to 237.50 ± 38.18 PE (p <0.05).

Long-term daily intragastric administration of resveratrol (2 mg / kg) for 7 days against the background of an ADMA-like model of gestosis in pregnant rats led to a significant increase in the level of microcirculation in the placenta to 368.73 ± 34.87 PE, which is significantly higher than in animals in the group with the introduction of L-NAME (p <0.05).

Thus, the obtained results convincingly indicate a pronounced correction of placental microcirculation disorders under conditions of the reproduced ADMA-like model of gestosis in pregnant rats with resveratrol.

Claims (1)

A method for correcting microcirculation disorders in the placenta, including reproducing an ADMA-like model of gestosis in pregnant rats of Wistar females daily for 7 days by intraperitoneal administration of L-nitro-arginine-methyl ether at a dose of 25 mg / kg, characterized in that it is administered against the background resveratrol intragastrically at a dose of 2 mg / kg.