| BackgroundPreeclampsia (preeclampsia, PE) is a serious disease of pregnancy, affecting 5-8% of pregnant women's health and endangers maternal and perinatal's lives. Its clinical manifestations are pregnancy after 20 weeks, persistent high blood pressure, proteinuria, and edema. If left untreated, preeclampsia after different length of the incubation period will be the sudden onset of preeclampsia, maternal and child endangering lives. Preeclampsia is one of the main causes of maternal mortality; the mortality rate was 2%-5%.Preeclampsia is currently considered a disease caused by complex, pluralistic and multiple mutations. Clotting, angiogenesis, placenta, immune regulation, lipid metabolism, oxidative stress regulation, and changes in the expression of related genes have known closely related to the pathogenesis of preeclampsia. The placenta factor is particularly important, because after removal of the placenta preeclampsia symptoms quickly improved.However, there is still a lack of effective means to predict preeclampsia. So, this paper intends to start with micro RNA and placental growth factor which significant expressed in placenta, hoping to identify the molecular marker to predict preeclampsia in early detection of preeclampsia, and ultimately early diagnosis and early treatment. First part:MicroRNA (miRNA) function discovery and research is one of the significant progresses in recent years in the field of life sciences.MiRNA is a large class of small non-coding RNA molecules involved in post-transcriptional gene regulation of eukaryotic cells. Sense strand of double-stranded mature miRNA into the RISC (RNA-induced silencing complex), binding to complementary sequences of the target gene mRNA 3'-untranslated region (untranslation region, UTR), the resulting degradation or translational inhibition of the target mRNA, and thus play miRNA target post-transcriptional regulation of gene expression. MiRNA gene transcription to produce a primary transcript, known as miRNA precursors (pri-miR), it is up to hundreds of nucleotides in length, and have a stem-loop structure of about 33bp, cut by the ribonuclease Dicer and Drosha and then becoming a mature miRNA. Many miRNAs have highly conserved function, tissue-specific expression, reflects that they have important physiological functions, plays an important role in the regulation of cellular processes including proliferation, differentiation and apoptosis in a variety of cell growth and development process. Expressing a protein often subject to a variety of miRNAs regulation, a single miRNA can also regulate the expression of various proteins. This feature may make a major breakthrough from the miRNA to study the pathogenesis of preeclampsia. Studies had shown that a large number of multiple miRNA expressed in the placenta. And preeclampsia may occur in the placenta with abnormal miRNA expression. Pineles, etc. as early preeclampsia and eclampsia and small for gestational age children (SGA) groups reported pathological diseases miRNA differential expressed in the placenta, the placenta also reported differences in miRNA expression in patients with severe preeclampsia. For a particular miRNA, scientists have launched a number of specific impact studies and preeclampsia placental development occurring right. In 2008, Roman A, etc. found 91 kinds of varying miRNA (38 down-regulated and 53 were up-regulated) in preeclampsia pregnant women compared with normal pregnant women, and come to a conclusion that these miRNA molecules had possibilities to become a symbol of preeclampsia diagnosis markers. But the impact of miRNA research on placental development and their specific mechanism of action are still very limited.This paper intends to proceed from the placenta to explore miRNA effects on placental trophoblast and preliminary screening of its substrate in preeclampsia patients, intend to have a deep understanding of pathogenesis of preeclampsia. Second part:Placental growth factor (placenta growth factor, PLGF) abundantly expressed in placenta, vascular endothelial growth factor one (Vascular endothelial growth factor, VEGF) family members. PLGF, on the one hand, promoted an autocrine manner trophoblast cell proliferation and differentiation:on the other hand regulated placental angiogenesis and physiological recast paracrine manner; moreover it can also play a synergistic role for VEGF, significantly increase its biological activity, and promote placental vascular development and maintain pregnancy placenta normal blood supply and function, made it adapt to the needs of maternal and fetal development.Currently, a large number of studies have shown that PLGF plays an important role in the formation and development of the normal pregnancy placenta, its abnormal secretory is closely related to preeclampsia. The pregnant women who were suffering from hypertensive disorders complicating pregnancy (severe preeclampsia) detected placental growth factor had a positive meaning for forecast, diagnosis and subsequent correlation process.PurposeFirst part:Through research, we will first clarify the affection of mir-181a on trophoblast proliferation, migration and invasion; then in the peripheral blood of pregnant, whether mir-181a can be used as molecular markers for early diagnosis of preeclampsia. Ultimately provide important theoretical support and a candidate target molecule for the development of preeclampsia and placental barrier mechanism and clinical early diagnosis and treatment.Second part:Explore the relationship between placental growth factor levels and hypertensive disorders complicating pregnancy (severe preeclampsia). It is intended to guide clinical work, to provide the basis and timing to terminate the pregnancy for some severe preeclampsia pregnant women, investigate the relationship of serum PLGF levels and HDCP degree.MethodFirst part:1. Compared with the normal pregnant women, mir-181a in maternal blood of the preeclampsia pregnant women was significantly differential expressed (Completed).2.Verify that the expression of mir-181a molecules in placental trophoblast (in situ hybridization).3.The affection of mir-181a on human trophoblast cell proliferation, invasion and migration (Transwell cell migration model, Matrigel cell invasion model, MTT method).4.The relevant difference data for statistical analysis (using spss18.0 analyzed) Second part:Fluorescence immunoassay analyzer detected serum PLGF level of 30 cases of pregnant women with severe preeclampsia and 30 normal pregnant women, and PLGF level of cases pregnant women who come to our hospital for prenatal care,100 cases pregnant women with hypertensive disorders complicating pregnancy (in it 40 cases Gestational hypertension,30 cases mild preeclampsia,30 cases severe preeclampsia) were selected to compare with 30 cases normal pregnancy women.ResultsFirst part:1. Verify the expression of mir-181a molecule in placental trophoblast cells2. Mir-181a can promote human placental trophoblast cells proliferation, invasion and migration. Second part:PLGF level in severe preeclampsia group was significantly lower than the control group, the difference was statistically significant; The levels of PLGF in serum of HDCP group were significant lower than those in normal control group; the level of PLGF showed significant difference in the gestational hypertensive group, mild preeclampsia group and severe preeclampsia group.ConclusionFirst part:1. Verify the expression of mir-181a molecule in placental trophoblast cells2. Mir-181a can promote human placental trophoblast cells proliferation, invasion and migration. Second part:PLGF level in severe preeclampsia group was significantly lower than the control group, detected PLGF levels in pregnant women have a positive meaning to predict and diagnosis severe preeclampsia and subsequent correlation process; the levels of PLGF in patients with HDCP decreased significantly when compared with normal pregnancy women, the level of PLGF dropped with the severity of the disease. Detection of maternal PLGF in serum can help the diagnosis and analysis of HDCP. |
PDF Full Text Request