RU2481103C1 - Method for placental microcirculation disorder correction in adma-like gestosis models in experiment by single ischemic episode - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to experimental pharmacology and may be used for the placental microcirculation correction in pregnant women. Substance of the method involves simulating gestosis in Wistar rats by the daily intraperitoneal introduction of L-nitro-arginine-methyl ester 25 mg/kg for 14th to 20th day of pregnancy. For the purpose of the placental microcirculation correction, what is used is a single 10-minute hind-limb ischemia by clamping the femoral artery in the upper one-third followed by reperfusion on the 21 days of pregnancy, 90 minutes prior to the microcirculation recording.

EFFECT: use of the declared method allows correcting the placental microcirculation disorders during the simulated pathology.

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Description

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

Closest to the claimed solution is a method for correcting hemocirculatory 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 of ADMA-eNOS-associated targets with L-arginine in experimental preeclampsia ”, Kuban Scientific Medical Bulletin, No. 1, 2010, pp. 85-92.

The main disadvantage of this method is that L-arginine is a direct competitor to ADMA and an increase in its concentration leads to an increase in the substrate for the formation of NO and activation of NO synthase due to the competitive displacement of ADMA. One of the leading pathophysiological factors in reducing the activity of endothelial NO synthase (e-NOS) and the development of gestosis is placental ischemia. An increase in the activity of NO synthase can be achieved with anti-ischemic agents. Therefore, the results of correction of hemocirculatory disorders in the placenta with an ADMA-like pathology model in pregnant animals using L-arginine are unsatisfactory.

The technical result of the invention is a method for the correction of hemocirculatory disorders in the placenta with an ADMA-like model of gestosis, including a single reproduction of 10 minutes of hind limb ischemia with anti-ischemic effect.

The technical result is achieved by the fact that against the background of gestosis simulation in an experiment, an intraperitoneal injection of pregnant female Wistar rats for 7 days with an ADMA-like blocker of endothelial NO synthase-N-nitro-L-arginine-methyl ester (L-NAME) at a dose of 25 mg / kg hemocirculatory disorders in the placenta are corrected by reproducing a single 10 minute ischemic episode of the hind limbs. This leads to a pronounced correction of microcirculation disorders in the placenta with a simulated pathology. This effect is associated with the mechanisms underlying the phenomenon of early ischemic preconditioning.

The method is carried out as follows.

The experiments were carried out on white pregnant rats of Wistar female females weighing 250-300 g. N-nitro-L-arginine methyl ether (L-NAME) was administered intraperitoneally at a dose of 25 mg / kg / day for 7 days (from 14 to 20 days of pregnancy ) Hind limb ischemia was reproduced on the 21st day of pregnancy once 90 minutes before vascular samples were performed by 10-minute compression of the femoral artery followed by reperfusion. The compression of the femoral artery was performed by applying a cuff to the upper third of the thigh. The control of the correctness of the cuff application was the absence of a pulse on the arteries of the leg.

On the 21st day of pregnancy under anesthesia, microcirculation in the placenta was measured. 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).

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

EXAMPLE OF SPECIFIC IMPLEMENTATION.

The blockade of NO synthase caused by 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 210.00 ± 21.80 PE (p <0.05).

Reproduction of a single ischemic episode 90 minutes before the registration of microcirculation 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 327.30 ± 17.20 PE, which is higher than in animals in the group with L- NAME (p <0.05).

Thus, the obtained results convincingly indicate a pronounced correction of microcirculation disorders in the placenta under the conditions of the similar model of gestosis reproduced by us by ADMA in pregnant rats by reproducing a single ischemic episode 90 minutes before the registration of microcirculation.

Claims (1)

A method for correcting hemocirculatory disorders in the placenta with an ADMA-like gestosis model, comprising reproducing a gestosis model in Wistar rats daily from the 14th to the 20th day of pregnancy by intraperitoneal administration of L-nitro-arginine-methyl ether at a dose of 25 mg / kg, characterized the fact that for the correction of microcirculation disorders in the placenta is used on the 21st day of pregnancy 90 minutes before the registration of microcirculation, a single reproduction of 10-minute ischemia of the hind limbs by clamping the femoral artery in the upper third with the last guide reperfusion.