RU2479872C1 - Method for correction of ischemic disorders caused by reperfusion liver injury - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: correction of ischemic disorders caused by reperfusion liver injury in experiment in white Wistar male rats involves modelling an ischemic and reperfusion liver injury. 30 Minutes before, L-norvalin arginase blocker 10 mg/kg is introduced intraperitoneally, and distant ischemic pre-conditioning is conducted. Then, another dose of L-norvalin arginase blocker is introduced immediately after liver ischemia.

EFFECT: effective correction of the hepatocellular damage ensured by minimising the oxidative stress effects.

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Description

The invention relates to medicine, in particular to experimental hepatopharmacology, and can be used to correct ischemic and reperfusion liver damage in an experiment.

The closest is a method for correcting hepatocellular damage by introducing the drug N ^ω -hydroxy-nor-L-arginine at a dose of 100 mg / kg 15 minutes before the onset of hepatic tissue ischemia and 15 minutes after the end of ischemia in the same dosage (Kaye M. Reid , Allan Tsung, Takahashi Kaizu, Geetha Jeyabalan, Atsushi Ikeda, Lifang Shao, Guoyao Wu, Noriko Murase and David A. Geller / Liver I / R injury is improved by the arginase inhibitor, N ^ω -hydroxy-nor-L-arginine / / Am J Physiol Gastrointest Liver Physiol 292: 512-517, 2007).

The main disadvantage of this method is that using N ^ω -hydroxy-nor-L-arginine it is not possible to achieve a significant reduction in the level of hepatocellular damage. To eliminate this drawback, an arginase blocker L-norvaline was used at a concentration of 10 mg / kg in combination with distant ischemic preconditioning.

The technical result of the invention is a method for the correction of ischemic disorders resulting from reperfusion injury to the liver, including the use of an arginase blocker L-norvaline at a dose of 10 mg / kg in combination with distant ischemic preconditioning.

The technical result is achieved by the fact that in the experiment 30 minutes before modeling reperfusion liver damage, they are corrected by intraperitoneal administration of an arginase blocker L-norvaline at a dose of 10 mg / kg, followed by repeated administration of the same dosage of the drug immediately after liver ischemia in combination with distant ischemic preconditioning, which leads to activation of the correction of ischemic reperfusion damage to the organ.

The method is as follows.

The experiments were carried out on white rats male Wistar line weighing 180-220 g. Latex turnstile is superimposed on the hepatoduodenal ligament of animals for 15 minutes. Remote preconditioning is performed before the turnstile is applied. The arginase blocker L-norvaline is administered intraperitoneally 30 minutes before the onset of ischemia at a dose of 10 mg / kg, the same dosage of the drug is administered immediately after removing the turnstile from the ligament. All manipulations are performed under anesthesia: intraperitoneal administration of chloral hydrate at a dose of 300 mg / kg. 24 hours after the experiment under anesthesia (chloral hydrate 300 mg / kg), animal blood is taken from the heart cavity for subsequent determination of serum transaminase levels. The studies were performed on a Vitalab Flexor E automatic biochemical analyzer (Netherlands) using reagents from Biocon and Human (Germany). Indicators ACT, ALT determined by the kinetic photometric method at a wavelength of 340 nm.

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

An example of a specific implementation.

The degree of hepatocellular ischemic damage was assessed based on the difference in serum transaminase levels in animals. The level of ACT in animals undergoing ischemia / reperfusion of the liver exceeded the indices of the intact group by 1.93 times, respectively, 100.0 U / L in intact and 193.0 U / L in animals after ischemia / reperfusion of the liver. The level of ALT in animals undergoing ischemia / reperfusion of the liver exceeded the indices of the intact group by 3.2 times, respectively, 62.1 U / L in intact and 196.8 U / L in animals after ischemia / reperfusion of the liver. In the group where the correction of ischemic and reperfusion damage to the liver was performed by the administration of 10 mg / kg L-norvaline in combination with distant ischemic preconditioning, the transaminases were as follows: ACT - 9.7 ± 2.2 U / L; ALT - 3.0 ± 0.4 U / L (table).

Indicators reflecting the correction of hepatocellular damage in combination with distant ischemic preconditioning with the introduction of L-norvaline at a dose of 10 mg / kg Groups of animals ACT Level (U / L) ALT Level (Unit / L) Intact 100.0 ± 1.8 62.1 ± 3.8 Ischemia / reperfusion 193.0 ± 27.1 * 196.8 ± 26.9 * Distant preconditioning + L-norvaline 10 mg / kg 9.7 ± 2.2 ** 3.0 ± 0 / 0.4 ** Note: * - p <0.05 - in comparison with intact, ** - p <0.05 - in comparison with ischemia-reperfusion

Thus, the obtained results allow us to ascertain the activation of the correction of hepatocellular ischemic damage by a combination of distant ischemic preconditioning with an arginase blocker L-norvaline at a dose of 10 mg / kg.

Claims (1)

A method for correcting ischemic disorders resulting from reperfusion injury to the liver, including modeling of ischemia / reperfusion of the liver, characterized in that in an experiment on white rats of the Wistar line males model ischemic and reperfusion injury to the liver, 30 minutes before this, the L-norvaline arginase blocker is administered intraperitoneally at a dose of 10 mg / kg and distant ischemic preconditioning is performed, then the same dose of L-norvaline arginase blocker is re-administered immediately after the end of liver ischemia.