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Ruzieva Nodira Khakimovna, Department of Obstetrics and Gynecologyy Pediatric Gynecology, Tashkent Pediatric Medical Institute E-mil: n-ruzieva@mail.ru
ENDOTHELIAL DYSFUNCTION AS ONE OF THE CAUSES IN THE DEVELOPMENT OF PRETERM LABOR
Abstract. Endothelial dysfunction is considered as a universal non-specific link in the pathogenesis of many diseases. The purpose of this study was to identify the features of regulation of endothelial function in pregnant women with a risk of premature birth. We examined 66 pregnant women with a habitual history of miscarriage (a risk group for premature births) in the dynamics of the gestational period (32-36 weeks). The control group consisted of 14 women with a physiological course of pregnancy at the same gestational age. The determination of DE in the blood was carried out by J. Hladovec, a tissue plasminogen activator (t-PA) using HUMAN reagents by ELISA. Studies have shown that all pregnant women with a risk of premature birth have a higher content of DE in the venous blood compared with the control group. Thus, in pregnant women with a risk of premature birth, we observe, against the background of endotheliocyte dysfunction, an increase in both anticoagulation factor and plasminogen activity inhibitor.
Keywords: endothelium, dysfunction, premature birth, systemic inflammatory reaction
Introduction. Endothelial dysfunction is considered as a universal non-specific link in the pathogenesis of many diseases. The development of endothelial dysfunction may be associated with a systemic inflammatory response [1; 2]. Tissue plasminogen activator (t-PA) is a specific marker for the development of endothelial dysfunction, through its endothelial cells are involved in the regulation of the hemostatic function of the endothelium [4]. It has now been established that hyperhomocysteinemia is a risk factor for vascular pathology, since even at low concentrations homocysteine (HZ) has a pronounced cytotoxic activity against the endothelium, induce apoptosis of endothelial cells [5; 6]. The manifestations of endothelial dysfunction, the direction and severity of changes in the formation ofindividual endothelial factors in various diseases differ [3; 4].
The purpose of this study is to identify the features of regulation of endothelial function in pregnant women at risk for preterm birth.
Materials and methods. We carried out a survey of 66 pregnant women with a habitual miscarriage in anamnesis (risk group for preterm birth) in the dynamics of the gestational period (32-36 weeks). The control group consisted of 14 women with a physiological course of pregnancy at the same time of gestation. Pregnant women held clinical and laboratory research methods. The age of the examined pregnant women ranged from 21 to 28 years. Analysis of the frequency and nature of extragenital diseases in the examined women showed a high frequency of their occurrence, in particular, SARS-81%, pathology of ENT organs -24%, diseases of the gastrointestinal tract -30.5%, diseases of the urinary system-35.5%. Determination of entodelia dysfunction in the blood was carried out by the method of J. Hladovec [6], tissue plasminogen activator (t-PA) with HUMAN reagents by ELISA. The level of homocysteine (HZ) and annexin A-5 was determined on a ROSH CO-
Section 4. Medical science
BAS-411 instrument using test systems. Statisti- Results and discussion. Studies have shown
cal analysis of the results was carried out in the that all pregnant women at risk for preterm birth
package of applied licensed programs Microsoft have a higher content of entodelia dysfunction in
Office 2010, Statistica for Windows 6.0 and Med- the venous blood compared with the control group
Calc v 7.4.4.1. (p < 0.05) (Table 1).
Table 1. - The content of endothelial dysfunction markers in venous blood in pregnant women with preterm birth
Groups Endothelio-cytescells/^l Thrombomodulin (ng/ml) Homocysteine ^mol/l PAI-1 plasminogen activator inhibitor (U/ml) Annexin A-5 (ng/ml)
Healthy n = 14 2.01±0.17 4.73±0.56 9.14 ± 0.79 4.41±0.33 0.87±0.09
Pregnant women with preterm birth n = 26 6.98±0.71 11.38±0.87* 19.02 ± 1.28 12.94±1.73* 5.41±0.98*
Note: * - reliability of values of p < 0.05 when compared with baseline values
Endothelial factors affecting fibrinolysis include a tissue plasminogen activator inhibitor (t-PA). When studying the blood levels of pregnant women with preterm birth of a plasminogen activator tissue inhibitor, data were obtained indicating that with this pathology of pregnancy, an increase in the content of specific PAI-1 is observed, increasing when compared with the group of women with physiological pregnancy. It was found that an increase in the level of PAI-1 was observed in 10(28.2%) pregnant women, with the physiological course of gestation and in 72(87.8%) pregnant women with preterm labor. Studies have shown that an increase in the blood content of PAI-1 in most pregnant women with preterm labor indicates the development of hemostatic and adhesive forms of endothelial dysfunction due to the combined effects of vascular wall damage factors such as adhesive proteins and platelet hyperactivity. Thus, in pregnant women with preterm birth, we observe, against the background of endothelial dysfunction, an increase in both the anticoagulant activity factor and the plasminogen activity inhibitor.
This condition apparently leads to the depletion of the level of natural anticoagulant-antithrombin III, an increase in the level of D-dimeter in the blood and is one of the reasons for the development of a thrombo-philic state and trobotic complications during preterm
birth. Noted various factors of damage to the vascular wall are accompanied by intensification of apoptosis and increased levels of annexin A-5. According to modern concepts, the important role ofapoptosis in the development of thrombophilic states is associated with a high procoagulatory potential ofapoptotic cells and mi-croparticles (phosphatidolserine). It has now been established that PAI-1 and thrombomodulin have properties to inhibit apoptosis. In pregnant women with preterm birth, an increase in the levels of inhibitors of apoptosis ofannexin A-5, PAI-1 and thrombomodulin can be regarded not only as an indicator of endothelial dysfunction, but also as a compensatory process aimed at reducing the severity ofthrombophilia, including by reducing the thrombogenic potential of endothelio-cytes, undergoing apoptosis. As a result ofthe research, it was found that all pregnant women compared with healthy women had a significant increase in the blood level of annexin 5 by 2.7 times when compared with pregnant women with the physiological course of gestation and 6 times compared with pregnant women with preterm birth. Since annexin A-5 is formed in the endothelium, it can be assumed that the damage and apoptosis of endotheliocytes leads to an increase not only in annexin A-5 in the blood, but also in the level of disqualified endotheliocytes, where its level exceeded the original values by 3.5 times.
It is known that the staged increase in the aggregation and coagulation parameters ofblood coagulation in pregnant women with a physiological course ofpreg-nancy reaches maximum values by the 3rd trimester, but is not accompanied by the activation of intravascular coagulation. This is mainly due to the sufficient activity of natural coagulation inhibitors that prevent the progression of blood clots and the consumption of the main components of coagulation. At the same
time, in preterm birth, we observe an imbalance in the hemocoagulation system due to endothelial cell dysfunction and the cellular link ofthe hemostasis system.
Consequently, the results of our research indicate that the study of the dependence of endothelial dysfunction on the profile of factors affecting the endothelium is a promising direction in the development of methods for the prevention and treatment of preterm birth.
References:
1. Belo L., Santos-Silva A., Rumley A., Lowe G., Pereira-Leite L., Quintanilha A., and Rebelo I. Elevated tissue plasminogen activator as a potential marker of endothelial dysfunction in pre-eclampsia: correlation with proteinuria // BJOG: An International Journal of Obstetrics and Gynaecology, 2002; 109(11): 1250-5.
2. Dolgushina V. F., Kurnosenko I. V., Mezenceva E. A., Feklyunina E. S., Astashkina M. V. Prognoz prezhdevremennyh rodov u beremennyh zhenshin s vnutrimatochnoj infekciej [Forecast of premature birth in pregnant women with intrauterine infection] // Sovremennye problemy nauki i obrazovaniya.-2017.- No. 2.
3. Gomes da Silva S., Simöes P. S., Mortara R. A., Scorza F. A., Cavalheiro E. A., da Graga Naffah-Mazzacoratti M., Arida R. M. Exercise-induced hippocampal anti-inflammatory response in aged rats // J. Neuroinflammation. 2013.- No. 10.- 61 p.
4. Skurk C., Walsh K. Death Receptor Induced Apo- ptosis. A New Mechanism of Homocysteine-Mediated Endothelial Cell Cytotoxicity // Hypertension 2004; 43: 1168.
5. Glukhova T. N. et al. Features of metabolic and cytokine homeostasis in pregnancy complicated by premature rupture of amniotic membranes / Glukhova T. N., Dyatlova L. I., Chesnokova N. P., Ponukalina E. V. // V congress of obstetrician-gynecologists of Russia: materials of the forum - M.,
2013.- P. 43-44.
6. Dyatlova L. I., Chesnokova N. P., Glukhova T. N. Patterns of qualitative and quantitative changes in the cellular composition of peripheral blood during pregnancy, complicated by premature discharge of amniotic fluid // Science and Modernity: Materials of the International Scientific and Practical Conference.- Ufa, 2014.- P. 165-169.
7. Medvinsky I. D., Serov V. N., Yurchenko L. N. Severe gestosis from the perspective of a systemic inflammatory response syndrome // Bulletin of intensive care. 2003.- 1.- P. 19-26.
8. Mikhailov A. V., Dyatlova L. I., Glukhova T. N. Management of preterm pregnancy, complicated by premature discharge of amniotic fluid // Mother and child: materials of XV All-Russian. Forum.- M.,
2014.- P. 125-126.
9. Petrishchev H. H., Berkovich O. A., Vlasov T. D. The diagnostic value of determining desquamated endothelial cells in the blood // Clinical laboratory diagnostics. 2001; 1: 51-2.
10. Petrishchev H. H., Vasina L. V., Vlasov T. D. and other Typical forms of endothelial dysfunction // Clinical laboratory laboratory. 2007; 18: 31-35.
