IPC classes for russian patent Method for correction of ischemic disorders caused by reperfusion liver injury. RU patent 2479872. (RU 2479872):
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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.
1 tbl, 1 ex
The invention relates to medicine, in particular to the experimental , and can be used for the correction of ischemic and reperfusion damage to the liver in the experiment.
The closest one is a method of correction of hepatocellular damage by injection of N ω-hydroxy-nor-L-arginine with the dosage of 100 mg/kg 15 minutes prior to the insufficiency of the liver tissue and 15 minutes after the end of ischemia in the same dosage (M. Kaye 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 with N ω-hydroxy-nor-L-arginine cannot lead to significant reduction of hepatocellular damage. For elimination of this lack used the blocker arginase L- in a concentration of 10 mg/kg in combination with the distant ischemic .
The technical result of the invention is a method of correction of ischemic disorders resulting from reperfusion injury of the liver, including blocker arginase L- at a dose of 10 mg/kg in combination with the distant ischemic .
The technical result is achieved by the fact that in the experiment the 30 minutes prior to the simulation of reperfusion damage of the liver is their correction introduction blocker arginase L- at a dose of 10 mg/kg with the subsequent re-introduction of the same doses of the drug immediately after liver ischemia in combined with the distant ischemic , which leads to activation of the correction of ischemic reperfusion damage to the body.
The method is as follows.
Experiments are performed on male white rats Wistar weight 180-220, Latex turnstile is superimposed on the hepato-duodenum bunch of animals for 15 minutes. Remote preconditioning produce to the imposition of the turnstile. Blocker arginase L- injected intraperitoneally 30 minutes before the start of ischemia in a dose of 10 mg/kg, the same dosage of the drug is injected immediately after removal of the turnstile with cords. All manipulations are performed under General anesthesia: intra-abdominal introduction chloral hydrate in a dose of 300 mg/kg After 24 hours after the experiment under anesthesia (hydrate 300 mg/kg) produced blood of animals from the cavity of the heart for subsequent determination of serum transaminase levels. Studies performed on the automatic biochemical analyzer « E» (the Netherlands) with the use of reagents company «Biocon» and «Human» (Germany). Indicators ACT, ALT defined by the kinetic photometrically at 340 nm.
At the statistical processing of data was calculated average value, the standard deviation value. Differences was considered significant at p<0.05.
An example of a specific implementation.
Assessment of the degree of hepatocellular ischemic damage was performed on the basis of the difference in levels of serum transaminases animals. The level of ACT of animals undergoing ischemia/ liver, exceeded the intact group of 1.93 times respectively 100,0 U/l in intact and 193,0 U/l in animals after ischemia/reperfusion liver. ALT level in the animals undergoing ischemia/ liver, exceeded the intact group 3.2 times, respectively 62,1 U/l in intact and 196,8 U/l in animals after ischemia/reperfusion liver. In the group where the correction was made ischemic and reperfusion damage to the liver introduction of 10 mg/kg L- in conjunction with the distant ischemic , his transaminase were the following: ACT of 9.7±2,2 U/l; ALT - 3,0±to 0.4 U/l (table).
Indicators reflecting correction of hepatocellular damage on the background of a combination of remote ischemic preconditioning with the introduction of L- at a dose of 10 mg/kg
Groups of animals
Level ACT (IU/l)
The level of ALT (U/l)
Intact
100,0±1,8
62,1 ħ 3.8
Ischemia/reperfusion
193,0±27,1*
196,8±26,9*
Distant preconditioning + L- 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 state the activation of correction of hepatocellular ischemic damage a combination of remote ischemic preconditioning with blocker arginase L- at a dose of 10 mg/kg
Method of correction of ischemic disorders arising from reperfusion injury of the liver, including modeling of ischemia/reperfusion of the liver, characterized in that experiment with white male rats Wistar model ischemic and reperfusion injury of the liver, 30 minutes before the intraperitoneally injected blocker arginase L- at a dose of 10 mg/kg and perform remote ischemic preconditioning, then re-enter the same dose of the antagonist arginase L- immediately after the insufficiency of the liver.
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