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NEW APPROACHES OF MORFOFUNKTIONAL PHARMACOLOGICAL CORRECTION OF VIOLATIONS OF CARDIOVASCULAR SYSTEM IN EXPERIMENTAL PREECLAMPSIA

Experimental Modeling ADMA-like preeclampsia administration to rats was performed by N-nitro-L-arginine methyl ester, from 14 to 20 days of pregnancy. The animals were observed increase in blood pressure, proteinuria, impaired microcirculation in the placenta, the violation of the regulation of vascular tone and destructive changes in the placenta of ischemic origin. Introduction of tetrahydrobiopterin, a selective inhibitor of arginase II of, recombinant erythropoietin, tadalafil, erythromycin, azithromycin, and playback systems polivitaminnomineralnyh distant ischemic preconditioning resulted in a pronounced correction of morphological and functional disorders arise when modeling the experimental preeclampsia. This was reflected in the reduction of blood pressure, reduction of proteinuria, increase of microcirculation in the placenta, the restoration of vasodilator function of blood vessels and prevent destructive phenomena in the placenta compared with a group of untreated animals, increasing the concentration of NO end-metabolites in plasma. These data suggest a pronounced correction of morphological and functional disorders arise when modeling ADMA-like preeclampsia study medication and the prospects for further research to find new drugs have endoteleoprotektivnymi properties for correcting the second half of pregnancy preeclampsia.

Иллюстрации

Figure 1.1. Kidney pregnant rats normal: small artery in the cortex is intact with no signs of hypertrophy of the walls, its endothelium; glomerular capillary basement membrane is thickened, the cellular inflammatory response is absent. H & E stain. X 280.

   

Figure 1.2. A.  The structure of an intact placenta. spongy structure (villous) layer (a) and the border area between naps and a layer of giant trophoblast (b) of the placenta intact animals: uniform blood circulation capillaries of the villi and mezhkapillyarnyh spaces, relatively monomorphic structure trophoblast, the continuity of the transition from villous trophoblastic layer in the layer; Ochre. hematoxylin and eosin. Fig-. X 200.

Figure 1.2. B.   The structure of an intact placenta. spongy structure (villous) layer (a) and the border area between naps and a layer of giant trophoblast (b) of the placenta intact animals: uniform blood circulation capillaries of the villi and mezhkapillyarnyh spaces, relatively monomorphic structure trophoblast, the continuity of the transition from villous trophoblastic layer in the layer; Ochre. hematoxylin and eosin. Fig-. X 200

 

Figure 1.3. A.  Kidney of pregnant rats with preeclampsia (pregnancy day 21). and - a spasm and hypertrophy of arterioles; b - a ball of anemia, capillary basement membrane thickened dramatically and have the form of wire loops (membranous glomerulopathy); Ochre. hematoxylin and eosin. Fig-. X 280.

 

Figure 1.3. B.   Kidney of pregnant rats with preeclampsia (pregnancy day 21). and - a spasm and hypertrophy of arterioles; b - a ball of anemia, capillary basement membrane thickened dramatically and have the form of wire loops (membranous glomerulopathy); Ochre. hematoxylin and eosin. Fig-. X 280.

Figure 1.4.A.   Pathological changes in the placenta in modeling ADMA-like preeclampsia. A - uneven blood filling spongy layer; B - vacuolar degeneration of giant trophoblast; foci of necrosis on the border of giant trophoblast and decidua tissue; degenerative changes, anemia decidual layer. Ochre. hematoxylin and eosin. Fig-. X 200.

 Figure 1.4.B.   Pathological changes in the placenta in modeling ADMA-like preeclampsia. A - uneven blood filling spongy layer; B - vacuolar degeneration of giant trophoblast; foci of necrosis on the border of giant trophoblast and decidua tissue; degenerative changes, anemia decidual layer. Ochre. hematoxylin and eosin. Fig-. X 200.

Figure 1.5.   Pathological changes in placental ischemia. A - a general view with extensive necrosis and hemorrhage in the labyrinth zone (LZ), B - and hemorrhagic necrosis of the lake in the LZ, B - a major focus of purulent detsiduita, tissue separation at the boundary of the placenta and the uterine wall. H & E stain. Fig-. X50 (A), X200 (B, C).

Table 1.1. Values of morphological and functional parameters in pregnant rats at modeling ADMA-like preeclampsia and reduced blood flow in the uterus (M ± m; n = 10).

Table 2.1. Effect of pharmacological agents that affect the way L-arginine - of NO - cGMP in the blood  pressure, CED and microcirculation in the placenta in the correction of ADMA-like preeclampsia in rats (M ± m; n = 10)

Table 2.2. Effect of pharmacological agents that affect the way L-arginine - NO - cGMP values of parameters a 12-hour proteinuria and urine output correction ADMA-like preeclampsia (M ± m; n = 10)

Figure 2.1. Study of the influence on NOx concentration in plasma and the expression of eNOS pharmacological agents that affect the way L-arginine - of NO - cGMP in the correction of ADMA-like preeclampsia.

Table 2.3. Effect of pharmacological agents that affect the way L-arginine - NO - cGMP to integral evaluation of the complex pathological changes in the kidney and placenta eNOS expression and the correction ADMA-like preeclampsia (n = 10)

Table 3.1. Effect of short episodes of ischemia-reperfusion and recombinant erythropoietin on blood pressure, CED, and on placenta mikrocirculation (M ± m; n = 10)

Table 3.2.  Effect of short episodes of ischemia-reperfusion and recombinant erythropoietin values of parameters a 12-hour proteinuria and diuresis in modeling ADMA-like preeclampsia (M ± m; n = 10)

Figure 3.1.Effect of short episodes of ischemia-reperfusion, and recombinant erythropoietin for NOx concentration in the plasma and in eNOS expression in endothelial correction ADMA-like preeclampsia.

Figure 3.2.A.   The placenta in animals with 10x playback of transient ischemic episodes on the background of ADMA-like preeclampsia. A - decidual layer: monomorphic structure, the absence of degenerative changes; B - even krovenapolnenie spongy layer; In - No degenerative changes trophoblast; Ochre. hematoxylin and eosin. Fig-. X 200.

Figure 3.2.B.   The placenta in animals with 10x playback of transient ischemic episodes on the background of ADMA-like preeclampsia. A - decidual layer: monomorphic structure, the absence of degenerative changes; B - even krovenapolnenie spongy layer; In - No degenerative changes trophoblast; Ochre. hematoxylin and eosin. Fig-. X 200.

Figure 3.2.C.   The placenta in animals with 10x playback of transient ischemic episodes on the background of ADMA-like preeclampsia. A - decidual layer: monomorphic structure, the absence of degenerative changes; B - even krovenapolnenie spongy layer; In - No degenerative changes trophoblast; Ochre. hematoxylin and eosin. Fig-. X 200.

Table 3.3. Effect of 10 min ischemia-reperfusion episodes of pathological changes of the complex and expression of eNOS in modeling ADMA-like preeclampsia (n = 10)

Figure 3.3 Effect of aminoguanidine (300 mg / kg) and glibenclamide (50 mg / kg) on blood pressure, CED, micro-circulation in the placenta and proteinuria in the correction of ADMA-like preeclampsia short episodes of ischemia-reperfusion.

Figure 3.4.Effect of aminoguanidine (300mg / kg) and glibenclamide (50 mg / kg) on the NOx concentration in plasma and the expression of eNOS in the correction ADMA-like preeclampsia short episodes of ischemia-reperfusion

Table 3.4. Effect of aminoguanidine and glibenklamina on complex pathological changes and the expression of eNOS in the correction of short episodes of ischemia-reperfusion of ADMA-like preeclampsia (n = 10)

Figure 4.1. Effect of erythromycin (30 mg / kg) and azithromycin (30 mg / kg) on blood pressure values, CED, micro-circulation in the placenta and proteinuria in the correction of ADMA-like preeclampsia.

Figure 4.2. Effect of erythromycin (30 mg / kg) and azithromycin (30 mg / kg) on the NOx concentration in plasma and the expression of eNOS in the correction ADMA-like preeclampsia short episodes of ischemia-reperfusion.

Table 4.1. Effect of erythromycin and azithromycin in the complex pathological changes and the expression of eNOS in placenta in modeling ADMA-like preeclampsia (n = 10)

Figure 5.1. Impact of the B9 vitamin (0,2mg / kg) combined use of vitamins B9 (0,2 mg / kg) and B6 (2 mg / kg) of drugs "Complivit® trimestrum 2 Trimester" (0.084 tab/kg) "Complivit® trimestrum 3 trimester" (Table 0.084 tab/kg) on blood pressure, CED, micro-circulation in the placenta and proteinuria in the correction of ADMA-like preeclampsia.

Figure 5.2. Effect of vitamin B9 (0,2 mg / kg), the combined use of vitamins B9 (0,2 mg / kg) and B6 (2 mg / kg) of drugs "Complivit® trimestrum Trimester 2" ( 0.084 tab/kg) and "Complivit® trimestrum 3 trimester" (0.084 tab/kg) in the NOx concentration in plasma and the expression of eNOS in the correction of ADMA-like preeclampsia.

Table 5.1. Effect of vitamin B9, combined use of vitamins B6 and B9, drugs "Complivit® trimestrum Trimester 2" and "Complivit® trimestrum trimester 3" in the complex pathological changes and the expression of eNOS in the correction of ADMA-like preeclampsia (n = 10)

Table 6.1. Integrated assessment of complex pathological changes in the kidney and placenta in the correction of ADMA-like preeclampsia (n = 10)

DOI: 10.18413/2500-235X -2016-2-3-11-27
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