ABSTRACT
Interactions of vascular endothelial growth factor (VEGF) with receptors VEGFR1/Flt1 and VEGFR2/Flk1, and those of angiopoietins (Ang-1, Ang-2) with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation (D15, D18 and D21). The rats were randomly assigned into 3 groups: normal group, model group [fetal growth restriction (FGR) model], and Bushen Yiqi Huoxue (BYHR) recipe treatment group (BYHR group, the pregnant rats with FGR were treated with BYHR recipe). Morphological analysis indicated that during initial villous formation, fetal nucleated erythrocytes (FNEs) appeared in maternal blood sinus (MBS). Subsequently, FNEs were surrounded by endothelial cells to form fetal capillary (FC) and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining (EIS) in normal and BYHR groups. Whereas, villous formation was suppressed, normal increase in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flk1 mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while decreased on D21 in model group as compared with normal group and BYHR group. Immunohistochemically, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.
ABSTRACT
Interactions of vascular endothelial growth factor (VEGF) with receptors VEGFR1/Flt1 and VEGFR2/Flk1, and those of angiopoietins (Ang-1, Ang-2) with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation (D15, D18 and D21). The rats were randomly assigned into 3 groups: normal group, model group [fetal growth restriction (FGR) model], and Bushen Yiqi Huoxue (BYHR) recipe treatment group (BYHR group, the pregnant rats with FGR were treated with BYHR recipe). Morphological analysis indicated that during initial villous formation, fetal nucleated erythrocytes (FNEs) appeared in maternal blood sinus (MBS). Subsequently, FNEs were surrounded by endothelial cells to form fetal capillary (FC) and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining (EIS) in normal and BYHR groups. Whereas, villous formation was suppressed, normal increase in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flk1 mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while decreased on D21 in model group as compared with normal group and BYHR group. Immunohistochemically, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.
Subject(s)
Animals , Female , Male , Pregnancy , Rats , Drugs, Chinese Herbal , Therapeutic Uses , Fetal Growth Retardation , Therapeutics , Neovascularization, Physiologic , Physiology , Placenta , Rats, Sprague-Dawley , Tobacco Smoke PollutionABSTRACT
<p><b>OBJECTIVE</b>To study the diagnostic value of heart rate variability (HRV) in heart dysfunction in children with beta-thalassemia major (β-TM)by examining the changes of HRV in β-TM children.</p><p><b>METHODS</b>A 24 hours Holter monitoring electrocardiogram (Holter) was performed in 21 children with β-TM and 15 healthy children (control group). The time domain and frequency domain indexes of HRV in the two groups were compared. The correlation between serum ferritin levels and HRV was evaluated.</p><p><b>RESULTS</b>The time domain indexes SDNN, rMSSD and PNN50 and the frequency domain indexes very low frequency (VLF), low frequency (LF) and high frequency (HF) in the β-TM group were significantly lower than in the control group (P<0.05). There was no correlation between serum ferritin level and HRV in children with β-TM.</p><p><b>CONCLUSIONS</b>The autonomic nerve dysfunction exists in children with β-TM. HRV analysis is useful in the prediction of early cardiac dysfunction in children with β-TM.</p>
Subject(s)
Adolescent , Child , Female , Humans , Male , Ferritins , Blood , Heart Rate , Physiology , beta-Thalassemia , BloodABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of Bushen Yiqi Huoxue Recipe (BYHR, a Chinese medical prescription for reinforcing Shen, replenishing qi and promoting blood circulation) on placental trophoblast apoptosis in fetal growth restricted (FGR) pregnant rat for the sake of explore its mechanism of action in treating FGR.</p><p><b>METHODS</b>FGR animal model was established by passive smoking, 32 pregnant rats were divided into four groups at random: the normal group, the model group, the Chinese medicine (CM) group (model rats treated by BYHR) and the Western medicine (WM) group (model rats treated by arginine). The histological change of placenta was examined with HE stain, the trophoblast apoptosis was detected by TUNEL and RT-PCR, and the expressions of Bcl-2 and Bax in the placenta were detected by immunohistochemical method.</p><p><b>RESULTS</b>Blood stasis and villous ischemia were seen in placenta of FGR model rats. Placental microcirculation was significantly improved in the CM group, but in the WM group only partially improved. The median apoptotic index of syncytial trophoblast cells in the four groups, in normal, model, CM, and WM order, was 45%, 75%, 57% and 70%, as compared with the model group, it was much lower in the normal group and the CM group (P < 0.01), but a similar level was shown in the WM group. No significant difference in mRNA and protein expressions of Bcl-2 and Bax was found among the four groups.</p><p><b>CONCLUSION</b>BYHR can improve the placental microcirculation in FGR rats to prevent excessive apoptosis through a mechanism other than the classical Bax/Bcl-2 apoptotic pathway, which needs further exploring.</p>