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of vascular cells [1; 5].Great value for a normal pregnancy and an important pathogenetic role in the development ofits complications plays von Willebrand factor. Its main function is to regulate the adhesion of platelets to the damaged vessel walls: it is the link between platelets and thrombogenic surface, and is the focal mechanism ofthe three units of the hemostasis system -vascular, platelet, coagulation. During pregnancy, increases the concentration of the von Willebrand factor. During pregnancy, it increases the concentration ofthe von Willebrand factor. Impaired production ofvon Willebrand factor associated with abnormal endothelial cells that plays an important role in the thrombogenicity and tromboresistance vessels [2].
Nearby studies found that women with preeclampsia and PONRP revealed an increase in blood levels of adhesive protein von Willebrand factor, and fibronectin. However, at risk for the development of thromboembolic complications should include pregnant women with pre-eclampsia, heart diseases, kidney disease, liver disease, obesity, diabetes, varicose veins, you need to survey markers of endothelial dysfunction Villebrand factor and fibronectin, direct markers of intravascular coagulation, natural coagulants and others [4;
5].Thus, according to the results of the research and analysis of the literature, we can recommend the use of markers of endothelial dysfunction, such as vascular endothelial growth factor and placental, and von Willebrand factor, and fibronectin for the prediction of placental abruption, which will enable early diagnosis and develop an adequate tactics Management of patients.
Findings Risk factors for the development of placental abruption include: infection, sexually transmitted infections (chlamydia, herpes simplex virus, cytomegalovirus, mycoplasma), threatened miscarriage I and II pregnancy, fetoplacental insufficiency.
Premature detachment of the placenta develops in the background of severe endothelial dysfunction, which is accompanied by an increase in the blood of pregnant vascular endothelial growth factor of 1.5 times and a reduction plat-sental growth factor of 1.9 times.
Violation imbalance findings endothelial dysfunction is accompanied by severe thrombosis, which is accompanied by an increase in von Willebrand factor of 1.4 times and 1.7 times of fibronectin.
References:
1. Volkov E.V., Kopylov Yu. The role of vascular growth factors in the pathogenesis of placental insufficiency//Obstetrics. Gynecology. Reproduktsiya. - 2013. - № 2 (7). - S. 29-33.
2. Nevzorova I.A. Egorova A.T., Salmin A.B., fat NV The role of endothelial dysfunction markers in the diagnosis of retinal detachment chorionic//Problems. Hynek., Akusha. and perinat. - 2015. - № 6 (13). - S. 49-53.
3. Kalkunte S.S., Mselle N. F., Norris W. E. et al. Vascular endothelial growth factor C facilitates immune tolerance and endo-vascular activity of human uterine NK cells at the maternal - fetal interface//J. Immunol. - 2009. - Vol. 182. - P. 4085-4092.
4. Kenny L.C., Broadhurst D.I., Dunn W., Brown M., North R.A., McCowan L. et al. Screening for Pregnancy Endpoints Consortium. Robust early pregnancy prediction of later preeclampsia using metabolomic biomarkers//Hypertension. -2010. - № 4 (56). - P. 741-749.
5. Rasmussen S., Irgens L. M. Occurrence of placental abruption in relatives//BJOG. - 2009. - Vol. 116. - P. 693-699.
Komilova Mastura Safarovna, Senior Research Scientist researcher, State Medical Institute.
Abu Ali Ibn Sina, Department of Obstetrics and Gynecology, Ministry of Health of the Republic of Uzbekistan Bukhara
Pakhomova Zhanna Evgenevna, Professor of the Tashkent Medical Academy, Republic of Uzbekistan.
E-mail: komilova1985@mail.ru
The reaction of systemic inflammatory response in premature detachment of normally situated placenta
Abstract: The basis of the development of abruption placentas in nulliparous women without hypertensive response syndrome is a systemic inflammatory response. Reaction of systemic inflammatory response characterized by increased TNF-a enhance in 2,6raz, IL-1^ in 3 times, IL-6, 8-fold, as well as index ratios TNFa/IL-10 at 4.1 times and reduces IL-10 in 1,5 times.
Keywords: endothelial dysfunction, cytokine, placenta, interleukin.
In recent years, numerous studies scientists are increas- sponse in the development of pregnancy complications, such ingly point to the importance of the systemic inflammatory re- as the habitual pregnancy loss, preterm delivery, placental in-
Section 7. Medical science
sufficiency syndrome, intrauterine growth retardation, intrauterine infection, preeclampsia [1; 5; 8]. Factors implementing systemic inflammatory response (SVR) are proinflammatory cytokines, products of oxidative stress, lipids, neutrophils and platelets. The development of the inflammatory cascade leading to disruption of placenta and subsequent pregnancy complications. The increasing concentration of proinflammatory cytokines such as tumor necrosis factor (TNF-a), interferon-y (IFN- y) associated with preterm birth, preeclampsia.
Reduction of anti-inflammatory cytokines: interleukin-4 (IL-4), IL-10 — with spontaneous abortion in the I trimester of pregnancy [2; 7; 10].
One of the leading factors of starting the SVR in pregnant women today believes the infection. Long, asymptomatic persistence of infectious agents in the body can affect human reproduction. The presence of chronic infection is diagnosed, many women with infertility and miscarriage. As a result of an imbalance between the body's defense mechanisms and the infectious agent is a change of the immune status, which leads eventually to the reactivation of the infection and the development of autoimmune disorders [3; 4; 9].
The main issues of development of the inflammatory response are under the control of pro-inflammatory cytokines produced by neutrophils, macrophages, T-cells. Proinflammatory cytokines are necessary for the elimination of pathogens from entering the body through a hotbed of neutrophils, macrophages, complement components, launching phagocytic, and bactericidal activity of others. Cytokines are involved in the process of implantation of trophoblast invasion, decidual-ization, and the development of the placenta and the immune tolerance of pregnancy. The protective role of pro-inflammatory cytokines is shown at their local work in the inflammation. On the other hand, generalized their products is the cause of damage to the organ and tissue levels. This activation is the initial link in the pathogenesis of endothelial lesions, synthesis of antiphospholipid antibodies and adhesion molecules with the subsequent development of thrombophilia and placental insufficiency in pregnancy [4; 6; 8].
Objective: Study the character of changes in the level of cytokines and tumor necrosis factor in nulliparous women with premature detachment of normally situated placenta (PDNSP), without hypertensive syndrome.
Materials and methods
We observed 65 pregnant women with gestational age 28-37 weeks. With PDNSP. Of these, the 1st group included 45 nulliparous pregnant women with mild PDNSP Group 2 (control) consisted of 20 healthy pregnant women with physiological pregnancy. Age of pregnant women was 19 to 34 years. Exclusion criteria were: severe extra genital pathology, multiple pregnancy, abnormalities of the uterus and uterine fibroids, hypertensive syndrome. For the study took 5.0 ml of blood in pregnant women from the cubital vein PONRP. In the blood serum of persons of both groups by ELISA examined the level of cytokines (IL-1fi, IL-6, IL-10) and tumor necrosis factor alpha (TNF-a) in the enzyme immunoassay analyzer (Shanghai Kehua Laborotory System Co.Ltd; KHB st-360) using a set of test systems (JSC «Vector-Best», Russia). Statistical analysis of the results was carried out on a PC using the software package universal «Excel» and «Statistica v.6» using standard parametric and nonparametric methods.
Results and discussion
Analysis of somatic diseases among pregnant women in the 1st gurppy showed that iron deficiency was 20 (45%), thyroid disease 12 (26.6%), chronic tonsillitis 8 (17.8%), chronic pyelonephritis 9 (20%). Healthy women with PDNSP accounted for 12 (26.6%). Noteworthy gynecological diseases among pregnant women with PDNSP inflammatory diseases of the pelvic organs were 13 (28.8%).
Moreover, carriers of infection, sexually transmitted Chlamydia, herpes simplex virus, cytomegalovirus accounted for 14 (31%). Analysis of obstetric history showed the following. The threat of interruptions I and II half of pregnancy occurred in 15 (33.3%) of pregnant women. Clinic PDNSP without labor occurred in 28 (62.3%), 6 (13.3%) — in the latent phase and in 11 (24.4%) — in the process of childbirth.
Table 1. - The cytokines in the blood of pregnant women with PDNSP
Cytokines pg/ml Group 1 (n = 45) Group 2 (n = 20)
IL-1fi 80,4±4,57* 27,1±2,33
IL-6 58,2±3,37* 7,3±0,52
TNF-a 69,7±4,12* 26,7±2,57
IL-10 6,3±0,40* 9,8±0,89
TNF-a/IL-10 11,1 2,7
Note: * — the differences with respect to the data of the control group p-value <0.001.
As can be seen from the table, all the pro-inflammatory cytokines in pregnant women in the first group was significantly increased compared with the control group. The greatest increase achieved by IL-6, TNF-a, compared with the control group. Thus, the content of IL-B1 6sostavilo first group: 58,2 ± 3,37 pg/ml; TNF-a 69,7 ± 4,12; IL-10 in-
creased to 80,4 ± 4,57; in comparison with the 2nd group, P <0.001. Whereas anti-IL-10, decreased slightly in the 1st group of pregnant women with PDNSP compared with the control group: 6,3 ± 0,40 pg/ml and 9,8 ± 0,89 respectively. In this way, PDNSP essentially initiates changes in cytokine levels in maternal blood. For pregnant women with PDNSP
an increase of proinflammatory cytokines compared with the control group: IL-1^ 3,0 times; IL-6-to 8.0-fold; FNO-a-2.6 times.
We also evaluated the relationships TNFa/IL-10. Thus, when the index PDNSP blood of pregnant increased 4.1 times. There is a single cytokine network placenta involved in reproductive processes throughout pregnancy ensuring the safety and development of the fetus. Disturbances in the intercellular signaling accompanies pathological course of pregnancy. When fetal growth retardation, pathogenesis of which is also associated with inadequate trophoblast invasion in the spiral arteries of the uterus wall, the amniotic fluid increases the level of TNF-a, thereby decreasing the content of granulocyte colony stimulating factor, granulocyte-macrophage colony stimulating factor, IL-1^.
TNF-a is a multifunctional cytokine with proinflammatory immunoregulatory properties. Is stable concentration of this cytokine notes throughout a normal pregnancy can positively affect its development. On the other hand, under the influence of TNF-a activated NK cells (NK-cells), are capable of lysing trophoblast. TNF-a promotes production of IL IL -1, —6, and has a strong chemo tactic effect on monocytes, participates in inflammatory responses, induces expression of adhesion molecules on the surface of vascular endothelial cells, which leads to increased adhesion of neutrophils, monocytes to the vascular wall.
TNF-a activates the blood coagulation system, leading to the development of disseminated intravascular coagulation, occurrence of local micro thrombosis in placentation with infarction and subsequent detachment of the placenta. IL, and TNF-a stimulate the release of arachidonic acid, and enhance the production of prostaglandins myometrium. IL -6 is the main mediator of the acute phase proteins of inflammation. Under the influence of the infection can lead to increased product development of prostaglandins and premature labor. Women with pregnancy habitual no carrying revealed high levels of IL -6 in the cervical canal.
Maintaining IL -1 at a low level is one of the factors contributing to the preservation of pregnancy. Deficiency of IL -1^, as a proangiogenic cytokine, may lead to disruption of placental angiogenesis in the early stages of gestation, and as a consequence, spontaneous miscarriage [6; 11; 12].
Interleukin-10 as an anti-inflammatory cytokine is able
to inhibit the cell-mediated immune responses, has a protective effect on the pregnancy. A reduction in the level of IL-10 women to terminate a pregnancy [5; 6].
It is known that increasing the ratio of TNF-a/IL-10 in women with chronic forms of DIC in serum and in scrapings of the endometrium. However, changes in the level of IL-10 in the serum of pregnant women with DIC syndrome is not established. Also, the set offset balance TNF-a/IL-10 in the direction of proinflammatory cytokines. Increased levels of cytokines in the I trimester of pregnancy, even at physiological her current can be regarded as one of the significant risk factors for placental insufficiency FI [10; 12].
Thus, through the development PDNSP nulliparous women who do not have hypertension syndrome probably is the activation of the systemic inflammatory response reactions. Perhaps this is due to the presence of foci of infection and carriers of sexually transmitted infections or with activation of autoimmune processes in the organization of pregnancy. There is a change in the content of cytokines and their ratio, which is accompanied by increase in pro-inflammatory cytokines: TNFa, IL-1^, IK-6, reduced inflammatory cyto-kine IL-10 as well as the increase in index ratio TNFa/IL-10. Of course, a change in the established cytokine status in the organization of women with PDNSP will be the trigger for subsequent biochemical molecular processes.
Thus, in accordance with modern concepts of pregnancy complications prognosis determined by the characteristics of immune reactions. In the course of pregnancy can affect both overly strong immune response, and lack of pro-inflammatory reactions. On this basis, the study of cytokine balance is important for the assessment of the immune response and the outcome of pregnancy for both mother and fetus.
Conclusions:
— The basis of the development of abruption placentas in nulliparous women without hypertensive response syndrome is a systemic inflammatory response.
— Reaction of systemic inflammatory response characterized by increased TNF-a enhance in 2,6raz, IL-1^ in 3 times, IL-6, 8-fold, as well as index ratios TNFa/IL-10 at 4.1 times and reduces IL-10 in 1,5 times.
— Changes in the cytokine balance can serve as markers of the development of abruption placentas still at the preclini-cal level.
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