12+

EFFECT OF PHARMACOLOGICAL PRECONDITIONING WITH INCRETINOMIMETICS EXENATIDE AND VILDAGLIPTIN ON THE SURVIVAL OF ISCHEMIC TISSUES

Introduction: Currently, much attention is paid to the pleiotropic effects of entretenimiento.

Purposes: Study of the protective effect exenatide and valdiation with pharmacological correction of ischemic myocardial damage, damage of liver and skin graft during the experiment.

Methods: During the experimental study we used a comprehensive approach to the study of the antiischemic effects of entretenimento: doksorubitsinola model of cardiomyopathy, hypo/reperfusion of the isolated heart, ischemia/reperfusion of the liver and the modeling of the skin flap on the supply leg.

Results and discussion: Exenatide (10 mcg/kg/day) and vildagliptin (0.2 mg/kg/day) demonstrate a cardioprotective effect on doxorubicinol model of pathology that is reflected in the decline in the rate of diastolic dysfunction (StТТI), respectively, to 5.3±0.1 standard units. and 6.5±0.2 standart units in comparison with the control group 8.3±0.1 standart units in the model hypo/reperfusion of the isolated hearts of rats, exenatide (10-6 mol/l) and vildagliptin (10-4 mol/l), prevent the decrease of left ventricular pressure (LG). Exenatide (10 µg/kg) and vildagliptin (0.2 mg/kg) prevent necrotization of the skin flap 1.5 and 1.3 times in comparison with the control group. In the model of ischemia/reperfusion of the liver exenatide possess dose related hepatoprotective effect. All protective effects of entretenimiento leveled combined with a blocker of ATP-sensitive potassium channels glibenclamide (0.4 mg/kg).

Conclusion: During the study it was found that exenatide dose of 10 µg/kg/day and vildagliptin dose of 0.2 mg/kg, have a pronounced cardioprotective, hepatoprotective, and a pronounced cytoprotective effect on a model of isolated skin flap on the supply leg. ATP-dependent potassium channels are effector mechanism in the implementation of the protective effects of entretenimiento.

Иллюстрации

Fig. 1. Dynamics of pressure in the left ventricle (mm. Hg.) with the imposition of rapid heart rhythm contractions (480 BPM) for 15 seconds. The concentration of Ca2+ in perfusate 5 mmol/L. Intact group (a), doxorubicin (20 mg/kg) (b)

Fig. 2.The content of creatine phosphokinase CPK-MB, LDH, MDA, DK, in the model gypo/reperfusion in isolated hearts of rats.

Note: * p< 0.05 compared with control.** – p< 0.05 compared with intact animals.

Table 1. Functional parameters of myocardium in gypo/reperfusion in isolated heart of rats (%of initial level) (M±m; n=10)

Note: LG – left ventricular pressure (mm. Hg.); +dp/dtmax maximal rate of reduction (mm Hg/sec); -dp/dtmax maximal rate of relaxation (mm Hg/h); HR – heart rate (beats/min).* - p<0.05 in comparison with the control group.

Table 2. Indicators of the level of transaminases in the simulation of Ieremii/reperfusion of the liver (U/l) (M±m; n=10)

Note: *–p < 0.05 compared with the group of intact animals; **– p < 0.05 in comparison with the false-operated group; 1– p>0,05 in comparison with the control group.

 Table 3. Survival rates of the isolated skin flap on the supply leg at 3, 7, 10 days after its modeling. (M±m; n=10)

Note:* - p<0,05 in comparison with the control group

Table 4. The influence of entretenimiento exenatide and vildagliptin on the performance of the contractile function of the hearts of rats under doxorubicinol cardiomyopathy (M±m; n=10)

Note: the LG – left ventricular pressure (mm. Hg); +dp/dtmax maximal rate of reduction (mm Hg/sec); -dp/dtmax maximal rate of relaxation (mm Hg/h); HR – heart rate (beats/min). Doxorubicin was administered intraperitoneally, 48 hours before the experiment. Entretenimiento and vildagliptin exenatide were administered twice with an interval of 24 hours, subcutaneously and intraperitoneally, respectively, * * p<0.05 compared with the group of intact animals;* - p<0.05 in comparison with control group.

Fig. 3. The impact exenatide (10 mg/kg/day) and vildagliptin (0.2 mg/kg/day) for the coefficient of diastolic dysfunction (StТТI), with doxorubicinol cardiomyopathy.

Note: ** p<0.05 compared with the group of intact animals;* - p<0.05 in comparison with control group.

Table 5. Cardioprotective action exenatide (10-6 mmol/l) and vildagliptin (10-4 mmol/l) with Hypo-reperfusion in isolated heart of rats (%of initial level)(M±m; n=10)

Note:the LG – left ventricular pressure (mm. Hg.St); +dp/dtmax maximal rate of reduction (mm Hg./sec); -dp/dtmax maximal rate of relaxation (mm Hg./h); HR – heart rate (beats/min).* - p<0,05 in comparison with the control group.

Fig. 4.The content of creatine phosphokinase CPK-MB and LDH in groups with exenatide (10 mg/kg/day.) and vildagliptin (0.2 mg/kg/day).

Note: ** p<0.05 compared with the group of intact animals;* - p<0.05 in comparison with control group.

Fig. 5. The contents of MDA and DC in homogenate in groups with exenatide (10 mg/kg/day.) and vildagliptin (0.2 mg/kg/day)

Note: ** p<0.05 compared with the group of intact animals;* - p<0.05 in comparison with control group

Table 6. Indicators of the level of transaminases in modeling of schemia/reperfusion of the liver (U/l) (M±m; n=10).

Note:*–p < 0.05 compared with the group of intact animals; **– p<0,05 in comparison with the false-operated group; 1 – p<0,05 in comparison with the control group.

Fig. 6.Morphological picture of the liver in a series of false-operated animals (a) and control group (b) micro photos. X400

Fig. 7 The impact of the exenatide and vildagliptin on a factor of diastolic dysfunction (StТТI), with doxorubicinol cardiomyopathy.

Note: ** p<0.05 compared with the group of intact animals;* - p<0.05 in comparison with control group.

Fig. 8. The content of CPK-MB, LDH, MDA, DK in the exenatide group (10 mg/kg/day.) and vildagliptin (0.2 mg/kg/day) in the model of Hypo/reperfusion in isolated hearts of rats.

Note: ** p<0.05 compared with the group of intact animals;* - p<0.05 in comparison with control group

Table 7. Protective action of exenatide and vildagliptin on transminase on the background of glibenclamide during ischemia/reperfusion of the liver (U/l). (M±m; n=10)

Note:*–p < 0.05 compared with the group of intact animals; **– p<0.05 in comparison with the false-operated group; 1 – p<0.05 in comparison with the control group.

Table 8. Protective action of exenatide and vildagliptin on the background of glibenclamide survival of skin graft (%). (M±m; n=10)

Note:*- p<0.05 in comparison with the control group

Fig. 9. Schematic representation of the proposed pathways by which GLP-1 may exert its cardiovascular actions. The combination of GLP-1 effects on the myocardium (i.e. apoptosis and necrosis prevention in cardiomyocytes through the activation of the RISK pathway, increased glucose metabolism, vasodilatory and anti-inflammatory actions) with GLP-1 metabolic and vascular effects at the systemic level contributes to cardiac survival and function improvement.

Note: cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; Cyt c, cytochrome c; DPP-4, dipeptidyl peptidase-4; ERK, extracellular signal-regulated kinase; GLUT, glucose transporter; GSK, glycogen synthase kinase; LDH, lactate dehydrogenase; MEK1/2, MAP kinase kinase; MPTP, mitochondrial permeability transition pore; NOS, nitric oxide synthase; PI3K, phosphatidylinositol 3-kinase; PKA, protein kinase A; PKB, protein kinase B; ROS, reactive oxygen species.

DOI: 10.18413/2313-8971-2017-3-4-132-150
Количество просмотров: 1543 (смотреть статистику)
Количество скачиваний : 956
Полный текст (HTML)Полный текст (PDF)К списку статейВ раздел
  • Комментарии
  • Список литературы

Пока никто не оставил комментариев к этой публикации.
Вы можете быть первым.

Оставить комментарий: