Čimbenici angiogeneze placente u zdravih i dijabetičnih trudnica

Blajić, Jozo (2007) Čimbenici angiogeneze placente u zdravih i dijabetičnih trudnica. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Diabetes is a syndrome which develops because of absolute or relative deficiency of insulin or because of its alternated way of acting, which results in a formation of hyperglycemia. Diabetes in pregnancy brings along numerous other problems for both a mother and a child. Diabetes includes hypoxia, hyperglycemia and may affect grow, preservation and function of fetoplacental blood vessels, angiogeneses. Any form of pathological changes of haemodinamic characteristics in mother, characteristics of maternal blood, and grow factors including: vascular endothelial grow factor VEGF, placental grow factor PlGF, insulin like grow factor IGF, free oxygen radicals, final products of glycolysation, cytokines and mediators of inflammation are known to damage function of endothelial barrier or have extreme angiogenic effect. Emphasis of this research is on the events which form fetoplacental vasculature, and the changes which result as a consequence of mothers diabetes mellitus (DM). Goal of this research is to determine levels of PlGF, VGEF and IGF-II in examined groups, to perform histopathological analysis of placental insertion and to compare it with PlGF values in complete, incomplete and absent transformation of blood vessels, to compare grow factors in a serum of a mother and umbilical serum, and to find a correlation between the weight of the placenta, newborn's weight and a level of individual grow factors. Materials and methods: this is a prospective study, which involves 42 pregnant women with a type 1 diabetes, while a control group consists of 34 healthy pregnant women. Blood samples were taken from pregnant women at regular examinations, in periods of 3 to 4 weeks during whole pregnancy, at the delivery and from the umbilical vein. From the serum VGEF, PlGF and IGF-2 were determined. Deliveries which were terminated with a C-section, a biopsy of placental bed was made and it was send for a histopathological examination. Type of the childbirth termination, newborn's weight, newborn's length, Apgar score, pH and acidobasic status from the umbilical vein were noted. Statistical analysis was performed with SPPS program. Results PlGF values progressively grow from the beginning of pregnancy up to the 31st week of pregnancy, when maximum values – level of PlGF were found between 27 -30 weeks of pregnancy. Values are not statistically significant in investigated groups. VEGF values during pregnancy are higher in pregnant women who suffered from diabetes then in healthy pregnant women, but statistically significant difference between investigated groups was found in a period of 27-31 weeks of pregnancy and immediately after the delivery. VEGFR-1 levels are higher in pregnant women with diabetes comparing to healthy pregnant women, but this was not found to be statistically significant. IGF values are higher in a group of pregnant women with diabetes comparing to healthy pregnant women, and they increase during pregnancy, but again this was not found to be statistically significant. General information, age of the pregnant woman, week when pregnancy was terminated, weight of the placenta, newborn's weight and Apgar score in investigated groups were found not to be of any statistical significance. PIGF levels show correlation in weeks of pregnancy, newborn's weight and weight of the placenta in pregnant women with diabetes and in healthy pregnant women. PlGF levels in umbilical vein are lower than PlGF levels from the mother's serum. Comparing values of the PlGF levels from the mother's serum and from the umbilical vein, a positive and statistically significant coefficient was obtained. A characteristic of the placental bed obtained from the pregnant women whose pregnancies were terminated by a C-section is that there were 17% of incomplete physiological changes. Characteristics of the placenta insertion, physiological changes comparing to the incomplete physiological changes are statistically significant comparing to the week of pregnancy was it was terminated, weight of the placenta and the newborn, PlGF levels in mother’s serum and from the umbilical vein. Conclusion: I must stress out great importance of regular monitoring of normoglycemia in pregnant women with diabetes, which results in minimal oscillations of hyperglycemia and hypoglycemia and by this in minimal oscillations of hypoxia, and a supervision of different pathological conditions in pregnancy, as well (hypertension etc.) which affect factors of placental angiogeneses, and by this prevalence of specific morphological appearance of the placenta in pregnant women with type 1 diabetes.

Abstract in Croatian

Šećerna bolest je sindrom koji nastaje zbog apsolutnog ili relativnog manjka ili promjenjenog djelovanja inzulina, a rezultat je hiperglikemija. Dijabetes u trudnoći donosi brojne probleme kako za majku tako i za dijete. Dijabetični milje uključuje hipoksiju, hiperglikemiju i može utjecati na rast održavanje i funkciju fetoplacentarnih krvnih žila, angiogenezu. Bilo koja patološka promjena hemodinamskih obilježja majke, svojstva majčinske krvi, te čimbenici rasta uključujući: vaskularni endotelni čimbenik rasta VEGF, placentni čimbenik rasta PlGF, inzulinu slični čimbenik rasta IGF, slobodni radikali kisika, završni proizvodi glikolizacije, citokini i medijatori upale zna se da oštećuju funkciju endotelne barijere ili imaju izrazit angiogeni učinak. Naglasak ovog istraživanja je na događajima koji oblikuju fetoplacentnu vaskulaturu, te na promjenama koje se javljaju kao posljedica majčinskog DM. Ciljevi istraživanja su odrediti razinu PlGF, VGEF i IGF u istraživanim skupinama, histološki analizirati ležište placente i usporediti sa vrijednostima PlGF u odnosu na potpunu, nepotpunu ili izostalu pretvorbu krvnih žila, te usporediti čimbenike rasta u serumu majke i umbilikalnom serumu i naći korelaciju između težine placente, težine novorođenčadi i razine pojedinih čimbenika rasta. Materijali i metode: studija je prospektivna, 42 trudnice s dijabetesom tipa l, a kontrolnu skupinu čine 34 zdrave trudnice. Uzimani su uzorci krvi kod trudnica u razmacima 3-4 tjedna tijekom trudnoće kod redovnih pregled, kod poroda i iz umbilikalne vene. Iz seruma su određivani, VGEF, PlGF i IGF-2. Kod poroda dovršenih carskim rezom učinjena je biopsija ležišta posteljice i histološki obrađivana. Zabilježen je i način dovršenja poroda, porodna težina, dužina novorođenčadi, Apgar index, pH i acidobazni status iz umbilikalne vene. Učinjena je statistička obrada po SPPS programu. Rezultati Vrijednosti PlGF progresivno rastu od početka trudnoće do 31. tjedna trudnoće, kada su nađene najviše vrijednosti - razina PlGF između 27 -30 tjedna trudnoće. Vrijednosti nisu statistički značajne u istraživanim skupinama. Vrijednosti VEGF tijekom trudnoće su više u trudnica s diabetesom u odnosu na zdrave trudnice, ali statitistički znakovita razlika između istraživanih skupina je nađena između 27-31 tjedna trudnoće i neposredno nakon poroda. Vrijednosti VEGFR-1 su više u trudnica s diabetesom u odnosu na zdrave trudnice ali nisu statistički značane razlike. Vrijednosti IGF su više u skupini trudnica s diabetesom u odnosu na zdrave trudnice i povećavaju se tijekom trudnoće, ali nema statističke značajnosti. Opći podaci, dob trudnice , tjedni dovršenja trudnoće, težina placente, novorođenačka težina i Apgar index u istraživanim skupinama nemaju statističke značajnosti. Razine PIGF pokazuje korelaciju u tjednima trudnoće, porodnoj težini i težini placente u trudnica s diabetesom i zdravih trudnica. Vrijednosti PlGF u umbilikalnoj veni su niže u odnosu na razinu PlGF seruma majke. Uspoređujući vrijednosti PlGF seruma majke i vene umbilikalis dobiven je pozitivan i statistički signifikantan koeficijent. Karakteristike ležišta placente u trudnica dobivenih kod poroda dovršenih carskim rezom su 17% nepotpune fiziološke promjene. Karakteristike ležišta placente, fiziološke promjene u odnosu na nepotpune fiziološke promjene su statistički značajne u odnosu na tjedne dovršenja trudnoće, težine placente i novorođenčadi, razine PlGF u majčinom i UV seruma. Zaključak: Ističem veliku važnost redovnog praćenje normoglikemije kod trudnica s dijabetesom koja rezultira minimalnim oscilacijama hiperglikemije i hipoglikemije a time i hipoksije, kao i nadzor raznih patoloških stanja u trudnoći (hipertenzija i dr.) koji utječu na čimbenike angiogeneze placente a time i na pojavnost specifičnog morfološkog izgleda placente u trudnica s dijabetesom tipa l .

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