Application of PPAR gamma agonist in preparation of medicine for preventing, relieving or treating preeclampsia

Abstract

The invention belongs to the field of biotechnology and medical technology, and particularly relates to application of a PPAR gamma agonist in preparation of a medicine for preventing, relieving or treating preeclampsia. Experiments find that placenta lipid metabolism abnormality of preeclampsia patients is closely related to PPAR gamma-mediated lipid synthesis increase and metabolic regulation imbalance in an anoxic environment, which shows as trophoblast invasion and migration dysfunction, while the PPAR gamma agonist rosiglitazone can relieve trophoblast dysfunction caused by hypoxia. The PPARgamma antagonist T0070907 can aggravate trophoblast dysfunction caused by hypoxia, and the PPARgamma agonist can be used for preparing the medicine for preventing, relieving or treating preeclampsia, so that preeclampsia treatment is realized, and the life quality and the survival rate of patients are further improved.

Description

Technical Field

[0001] The present invention belongs to the field of biotechnology and medical technology, and particularly relates to the use of a PPARγ agonist in preparing a drug for preventing, alleviating or treating preeclampsia. Background Art

[0002] Preeclampsia (PE) is a systemic syndrome unique to pregnancy, characterized by new-onset hypertension and proteinuria. It has an incidence of 5% to 10% and is a leading cause of maternal and perinatal mortality. The critical pathophysiological stage begins in early pregnancy: insufficient invasion of placental trophoblasts leads to shallow placental implantation. Placental ischemia and hypoxia trigger the release of large amounts of anti-angiogenic factors, such as soluble vascular endothelial growth factor receptor-1 (sFlt-1) and soluble endoglin (sEng), leading to systemic maternal endothelial dysfunction, hypertension, and multi-organ damage. It is currently believed that placental-derived lipid metabolism disorders, inflammation, and oxidative stress contribute to this pathological process, but specific treatments targeting the underlying etiology are still lacking.

[0003] Existing medications for alleviating or treating preeclampsia primarily focus on symptomatic blood pressure reduction, anticoagulation, and promotion of fetal lung maturation, such as labetalol, low-molecular-weight heparin, and glucocorticoids. While these regimens can temporarily control blood pressure and prolong gestational age, they cannot reverse defects in placental vascular remodeling and are associated with side effects such as fetal growth restriction and liver and kidney damage. Therefore, in-depth research into the molecular regulatory mechanisms of PE and the development of substances that improve trophoblast function are crucial for the prevention and treatment of preeclampsia. Summary of the Invention

[0004] To address the above-mentioned problems, the present invention provides a use of a PPARγ agonist in the preparation of a drug for preventing, alleviating or treating preeclampsia. The present invention has experimentally found that abnormal placental lipid metabolism in patients with preeclampsia is closely related to increased lipid synthesis and imbalanced metabolic regulation mediated by PPARγ under hypoxic conditions, manifested as trophoblast invasion and migration dysfunction. The PPARγ agonist rosiglitazone can alleviate trophoblast dysfunction caused by hypoxia, while the PPARγ antagonist T0070907 can aggravate trophoblast dysfunction caused by hypoxia. PPARγ agonists can be used to prepare drugs for alleviating or treating preeclampsia.

[0005] To achieve the above purpose, the specific technical solutions of the present invention are as follows: In a first aspect, the present invention provides use of a PPARγ agonist in the preparation of a drug for preventing, alleviating or treating preeclampsia.

[0006] Furthermore, the PPARγ agonist is used to enhance the migration ability of human chorionic trophoblast cells under hypoxic conditions.

[0007] Furthermore, the PPARγ agonist is used to enhance the invasive ability of human chorionic trophoblast cells under hypoxic conditions.

[0008] Furthermore, the human chorionic trophoblast cells are HTR-8 / SVneo.

[0009] Furthermore, the PPARγ agonist is rosiglitazone, GW1929, darglitazone, saikosaponin A or MBX-102 acid; the CAS number of the rosiglitazone is 122320-73-4, the CAS number of the GW1929 is 196808-24-9, the CAS number of the darglitazone is 141200-24-0, the CAS number of the saikosaponin A is 20736-09-8, and the CAS number of the MBX-102 is 23953-39-1.

[0010] Furthermore, the dosage form of the drug is an oral preparation.

[0011] The second aspect of the present invention provides a drug for preventing, alleviating or treating preeclampsia, wherein the only effective active ingredient of the drug is the above-mentioned PPARγ agonist and a solvent.

[0012] Furthermore, the PPARγ agonist is rosiglitazone, and the CAS number of the rosiglitazone is 122320-73-4.

[0013] Furthermore, the concentration of rosiglitazone in the drug is 5mM~15mM.

[0014] Furthermore, the solvent is DMSO.

[0015] Compared with the prior art, the present invention has the following beneficial effects: The present invention discloses the use of PPARγ agonists in the preparation of drugs for preventing, alleviating or treating preeclampsia. The present invention systematically explores the relationship between abnormal lipid metabolism and trophoblast dysfunction under hypoxic environment through three levels: clinical sample analysis, animal model construction and in vitro cell experiments. Through experiments, it was found that abnormal placental lipid metabolism in patients with preeclampsia is closely related to the increase in lipid synthesis and metabolic regulation imbalance mediated by PPARγ under hypoxic environment, which manifests as trophoblast invasion and migration dysfunction. The PPARγ agonist rosiglitazone can alleviate the trophoblast dysfunction caused by hypoxia, and the PPARγ antagonist T0070907 will aggravate the trophoblast dysfunction caused by hypoxia. PPARγ agonists can be used to prepare drugs for preventing, alleviating or treating preeclampsia, so as to achieve the prevention and treatment of preeclampsia and further improve the quality of life and survival rate of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0017] Figure 1 Figure 3: Lipid deposition in placental tissue of pregnant women; Figure A shows lipid deposition in placental tissue of PC group; Figure B shows lipid deposition in placental tissue of PE group; Figure C shows the statistical diagram of lipid deposition in placental tissue of PC group and PE group; Scale bar: 50 μm; *** indicates the difference between the two groups. P <0.001.

[0018] Figure 2 Figure 3: Lipid deposition in rat placenta and fetal status. Figure A shows lipid deposition in rat placenta in the Sham group. Figure B shows lipid deposition in rat placenta in the Rupp group. Figure C shows a statistical graph of lipid deposition in rat placenta in the Sham and Rupp groups. Figure D shows the size of fetuses in the Sham and Rupp groups. From left to right, the 1st to 6th fetuses are from the Sham group, and the 7th to 12th fetuses are from the Rupp group. Below is a 20 cm ruler. Figure E shows the weight of fetuses in the Sham and Rupp groups. Scale bar: 50 μm. *** indicates differences between the groups. P <0.001, ** indicates the difference between the indicated groups P <0.01.

[0019] Figure 3 Figure 3 shows lipid deposition in trophoblasts of the normal group and the hypoxia group. Figure A shows lipid deposition in trophoblasts of the normal group. Figure B shows lipid deposition in trophoblasts of the hypoxia group. Figure C shows the statistical diagram of lipid deposition in trophoblasts of the normal group and the hypoxia group. Scale bar: 50 μm. *** indicates differences between the groups. P <0.001.

[0020] Figure 4 Figure 2: Changes in lipid metabolism indicators in trophoblasts in the normal and hypoxia groups; Figure A shows the mRNA expression levels of lipid metabolism indicators in trophoblasts in the normal and hypoxia groups; Figure B shows the mRNA expression level of PPARγ in placenta tissue of pregnant women; Figure C shows the mRNA expression level of PPARγ in placenta tissue of rats; Figure D shows the correlation analysis between the weight of pregnant women and the mRNA expression level of PPARγ in their placenta tissue; *** indicates the difference between the groups shown P <0.001.

[0021] Figure 5Figure 2 is the protein expression of p-PPARγ and PPARγ in trophoblasts of the normal group and the hypoxia group; Figure A is the protein expression of trophoblasts of the normal group and the hypoxia group; Figure B is the quantitative analysis of trophoblast protein expression in the two groups; *** indicates the difference between the groups shown P <0.001.

[0022] Figure 6 Figure 2: Changes in the migration and invasion abilities of trophoblasts in the control group (Control group), the hypoxia group (Hypoxia group), the hypoxia + PPARγ agonist group (Hypoxia + Rosiglitazone group), and the hypoxia + PPARγ antagonist group (Hypoxia + T0070907 group). Figure A shows the migration abilities of trophoblasts in the four groups, with the upper row of images showing the images at 0 h and the lower row of images showing the images at 24 h. Figure B shows the invasion abilities of trophoblasts in the four groups. Figure C shows the statistical graph of the migration abilities of trophoblasts in the four groups. Figure D shows the statistical graph of the invasion abilities of trophoblasts in the four groups. Scale bar: 500 μm. *** indicates differences between the groups. P <0.001.

[0023] Figure 7 The results show that PPARγ expression in trophoblasts was verified after transfection with PPARγ interference fragments. A shows the expression of green fluorescence in trophoblasts after transfection with si-PPARγ under a microscope. Scale bar: 200 μm. B shows the expression of PPARγ protein. The upper row of pictures shows PPARγ protein, and the lower row shows the internal reference protein. C shows the statistical graph of PPARγ protein expression. D shows the statistical graph of PPARγ mRNA expression. *** indicates the difference between the groups. P <0.001, ns indicates no significant difference between the groups.

[0024] Figure 8 Figure 3: Changes in the migration and invasion abilities of trophoblasts in the Hypoxia, si-PPARγ, and si-PPARγ+Rosiglitazone groups. Figure A shows the migration abilities of trophoblasts in the three groups, with the upper row showing the images at 0 h and the lower row showing the images at 24 h. Figure B shows the invasion abilities of trophoblasts in the three groups. Figure C shows the statistical graph of the migration abilities of trophoblasts in the three groups. Figure D shows the statistical graph of the invasion abilities of trophoblasts in the three groups. Scale bar: 500 μm. *** indicates differences between the groups. P <0.001, ns indicates no significant difference between the groups. DETAILED DESCRIPTION

[0025] The specific embodiments of the present invention are described in detail below, but it should be understood that the scope of protection of the present invention is not limited by the specific embodiments. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work are within the scope of protection of the present invention. The experimental methods described in the embodiments of the present invention are conventional methods unless otherwise specified, and the materials, reagents, etc. used in the following embodiments can be obtained from commercial sources unless otherwise specified.

[0026] Preeclampsia is a systemic syndrome unique to pregnancy, characterized by new-onset hypertension and proteinuria. It is a leading cause of maternal and perinatal mortality. The critical pathophysiological stage begins in early pregnancy: insufficient placental trophoblast invasion leads to shallow placental implantation. Placental ischemia and hypoxia trigger the release of large amounts of anti-angiogenic factors, such as soluble vascular endothelial growth factor receptor-1 (sFlt-1) and soluble endoglin (sEng), leading to systemic maternal endothelial dysfunction, hypertension, and multi-organ damage. Existing medications for the relief or treatment of preeclampsia primarily focus on symptomatic antihypertensive therapy, anticoagulation, and fetal lung maturation. While these strategies can temporarily control blood pressure and prolong gestational age, they cannot reverse the defects in placental vascular remodeling and are associated with significant toxic side effects. Therefore, in-depth research into the molecular regulatory mechanisms of preeclampsia and the development of agents that improve trophoblast function are crucial for the prevention and treatment of preeclampsia.

[0027] The present invention provides a use of a PPARγ agonist in the preparation of a drug for preventing, alleviating, or treating preeclampsia. The present invention has experimentally discovered that abnormal placental lipid metabolism in patients with preeclampsia is closely related to increased PPARγ-mediated lipid synthesis and imbalanced metabolic regulation under hypoxic conditions, manifesting as trophoblast invasion and migration dysfunction. The PPARγ agonist rosiglitazone can alleviate trophoblast dysfunction caused by hypoxia, while the PPARγ antagonist T0070907 can aggravate trophoblast dysfunction caused by hypoxia. Therefore, PPARγ agonists can be used to prepare drugs for the prevention and treatment of preeclampsia, further improving patients' quality of life and survival rate.

[0028] Example 1: 1. Materials and Methods 1. Sample source and clinical data Specimens were collected from 30 pregnant women with PE and 30 healthy pregnant women who delivered at the Ningxia Medical University General Hospital between October 2020 and November 2021. Inclusion criteria included singleton pregnancy, gestational age confirmed by first-trimester ultrasound, and no history of smoking or drinking. Exclusion criteria included major pregnancy complications such as chronic hypertension, diabetes, and autoimmune diseases. Basic data collected included age, gestational age, blood pressure, and body mass index (BMI). The study protocol was approved by the Ningxia Medical University Ethics Review Committee, and informed consent was obtained from the patients.

[0029] Animal Model: 14-day pregnant Sprague-Dawley rats were randomly divided into a sham-operated group (Sham group) and a reduced uterine blood flow group (Rupp group). Under anesthesia, a laparotomy was performed along the midline of the lower abdomen. Silver clips (0.203 mm ID) were placed in the lower aorta near the iliac bifurcation. Silver clips (0.1 mm ID) were also placed in the left and right uterine arteries. Uterine artery perfusion was reduced to 40% ± 5% of baseline, and postoperative layer-by-layer closure was performed. The sham-operated group underwent surgery alone without the use of silver clips. The study protocol was approved by the Medical Research Ethics Review Committee of the General Hospital of Ningxia Medical University.

[0030] 2. Reagents and instruments Fetal bovine serum (Absin, Shanghai), RPMI Medium 1640 Basic (Gibco, Beijing), cell-specific modified Oil Red O staining kit (Solebol, Beijing), Oil Red O dye (Sigma), crystal violet stain (Sevier, Wuhan), SGExcel FastSYBR qPCR master mix (Sangon, Shanghai), Rosiglitazone (MCE), T0070907 (MCE), fluorescence quantitative gene amplification instrument (Analytik Jena), CO2 cell culture incubator and microcentrifuge (Eppendorf), fluorescence slide scanner (TissueGnostics), PPARγ antibody (Abcam), Lipo-fectamineTM3000 (Thermo Fisher Scientific), PPARγ (phospho Ser112) antibody (Biolong), PPARγ interference fragment (Jima, Shanghai).

[0031] 3. Sample collection Placental tissue samples should be collected within 5 minutes of fetal delivery. A 1-cm diameter tissue block should be obtained from the central area of ​​the maternal face using sterile biopsy forceps (avoiding visible calcifications and infarcts). The sample should be rinsed with a gradient of 4°C pre-chilled phosphate-buffered saline (PBS, pH 7.4) and placed on sterile absorbent filter paper to absorb surface moisture before use.

[0032] 4. Cell culture and grouping The human chorionic trophoblast cell line HTR-8 / SVneo was obtained from the Shanghai Fudan Cell Bank.

[0033] HTR-8 / SVneo cells were cultured in RPMI1640 medium supplemented with 10% v / v fetal bovine serum (FBS) and a 1% penicillin-streptomycin mixture (100×) at 37°C, 5% CO2. The medium was changed daily, and cells were passaged when the cell density reached 80%–90%. For the hypoxia group, when the cell density reached 70%, the medium was changed to antibiotic-free medium. The culture flask was placed in a sealed hypoxia bag with an oxygen concentration of 1% v / v and cultured at 37°C for 24 hours. For the control group, cells were cultured normally.

[0034] 5. Experimental Grouping Human placental tissue grouping: The collected human placental tissues were divided into (1) pregnancy control group (PC group); (2) preeclampsia group (PE group).

[0035] The rat placenta tissues were divided into the following groups: (1) Sham group; (2) Rupp group, with 6 rats in each group.

[0036] Cells were grouped as follows: (1) Normal control group (Control group): cultured under normal conditions; (2) Hypoxia group (Hypoxia group): cultured under hypoxia; (3) Hypoxia + PPARγ agonist group (Hypoxia + Rosiglitazone group): cultured under hypoxia with the addition of 4 μL / mL PPARγ agonist Rosiglitazone (10 mM); (4) Hypoxia + PPARγ antagonist group (Hypoxia + T0070907 group): cultured under hypoxia with the addition of 2 μL / mL PPARγ antagonist T0070907 (10 mM). Groups (3) and (4) were cultured for 48 h before subsequent experiments.

[0037] 6. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) Total RNA was extracted from cultured cells and placental tissue using a cell / tissue total RNA rapid extraction kit (New Cyme). After testing the RNA purity and concentration (A260 / A280 ratio), a 20 μL reaction system was prepared according to the instructions of the reverse transcription kit (Takara). The total amount of RNA used in the system was 1500 ng. After reverse transcription, the expression level of mRNA was detected using the SYBR Green method. GAPDH As an internal reference, according to formula 2 −ΔΔCt The final results were analyzed and calculated. The primer sequences are shown in Table 1.

[0038] Table 1 RT-qPCR primer sequences 7. Cell Oil Red O Staining The cells were stained using an Oil Red O staining kit (purchased from Beijing Solebao Company), and the specific operations were performed according to the kit instructions.

[0039] 8. Oil Red O staining of sections Sections were fixed in 4% v / v paraformaldehyde at room temperature for 15 minutes. After fixation, they were rinsed in PBS for 3 × 5 minutes. Sections were rinsed in 60% v / v isopropanol for 20 seconds (accurate timing). Oil Red O working solution was added and the sections were stained for 30 minutes at room temperature in the dark. Sections were briefly differentiated in 60% v / v isopropanol, and excess dye was discarded. Sections were rinsed in PBS for 3 × 5 minutes. Sections were counterstained in hematoxylin for 1.5 minutes, followed by 3 × 5 minute rinses in PBS. Sections were mounted with glycerol-gelatin. Subsequent observation and image acquisition were performed.

[0040] 9. Transwell experiment HTR-8 / SVneo cells with good growth status were selected and starved for 24 hours by adding basal culture medium. Matrigel was placed at 4°C to melt overnight. PBS and Matrigel were diluted in a ratio of 8:1 using a pre-cooled pipette tip. 60 μL of diluted Matrigel was evenly spread on the bottom of the Transwell chamber and placed in a 37°C incubator for 3 hours. Unbound Matrigel was then aspirated. 100 μL of basal culture medium was added to the chamber and the culture plate was placed in a 37°C incubator for 30 minutes for hydration. Cells were resuspended in basal culture medium and the cell number was adjusted (1×10 5 ) and then inoculated into the upper chamber of a Transwell chamber. Add 500 μL of complete culture medium containing 10 v / v% fetal bovine serum (FBS) to the lower chamber of a 24-well plate. Incubate the culture plate in a 37°C, 5% CO2 incubator for 48 hours. After the incubation period, aspirate the culture medium. Add 4 v / v% paraformaldehyde to fix the cells for 15 minutes. Wash with PBS three times for 5 minutes each. Stain with crystal violet solution for 20 minutes. After washing with PBS, gently wipe away any non-migrated cells in the chamber with a cotton swab. Observe the number of invasive cells under an inverted microscope and take photos.

[0041] 10. Cell scratching On the bottom of a six-well plate, use a marker to draw three evenly spaced, parallel horizontal lines along a ruler as reference marks. Once cells are confluent, use a 200 μL pipette tip to make three vertical scratches perpendicular to the marked lines on the bottom plate. Wash the cells three times with PBS, add medium containing 2% v / v FBS and the test drug, and immediately photograph the cells as a 0-hour control. After incubating the cells in an oxygen-deficient environment for 24 hours, remove them and photograph them. Use ImageJ software to analyze cell migration distance and scratch area, and calculate the healing rate.

[0042] 11. Western Blot Cultured cells were harvested on ice, and proteins were extracted using a total protein extraction kit (Keygen Biotechnology). After quantification by the BCA assay (Keygen Biotechnology), the cells were denatured by boiling in protein loading buffer at 99°C for 10 minutes. The cells were subjected to low-temperature SDS-PAGE gel electrophoresis, followed by low-temperature wet transfer for 2 hours, blocking with 5% w / v BSA for 4 hours, incubation with the primary antibody (1:1000) at 4°C overnight, membrane washing, and incubation with the secondary antibody (1:5000) for 1.5 hours. β-actin was used as an internal control, and the relative expression of the target protein was determined using a Touch Imager electronic slide imaging system. Grayscale values ​​were calculated using system software.

[0043] 12. Cell transfection HTR-8 / SVneo cells were seeded in culture dishes. When the cell density reached 60%, transfection was performed strictly according to the Lipofectamine™ 3000 kit instructions. 5 μg of si-NC, si-PPARγ1, si-PPARγ2, or si-PPARγ3 were added to 125 μL of serum-free medium, mixed, and incubated at room temperature for 5 minutes. Then, 5 μL of Lipofectamine™ 3000 was mixed with 125 μL of serum-free medium and incubated at room temperature for 5 minutes. After mixing, the mixture was incubated at room temperature for 20 minutes. Each well of a 6-well plate was filled to 1.5 mL with serum-free medium and incubated in a constant temperature incubator. 24 hours after transfection, the medium was replaced with 7% v / v fetal bovine serum. After transfection, the cells were divided into (1) Hypoxia group (2) Hypoxia group after transfection with si-PPARγ interference fragment (si-PPARγ group) (3) Hypoxia group after transfection with PPARγ interference fragment and addition of Rosiglitazone (si-PPARγ+Rosiglitazone group).

[0044] 13. Statistical analysis All data are quantitative data, and the data are expressed as mean ± standard deviation ( ±s The comparison between the two groups was performed by t One-way analysis of variance (ANOVA) was used for multiple group comparisons, and SNK-q test was used for further pairwise comparisons. P The difference was considered statistically significant when the value was ≤0.05.

[0045] 2. Experimental Results 1. General Information Comparison of the two groups of pregnant women revealed that the BMI of the PE group was significantly higher than that of the normal pregnancy group ( Table 2 ).

[0046] Table 2 Comparison of basic information of pregnant women in the two groups [n=30, ( ±s)] 2. Lipid deposition in placental tissue of the PE group like Figure 1 As shown, the placenta tissue sections were stained with Oil Red O, and there was more lipid deposition in the placenta of PE patients (N=3) ( P <0.001), and the PC group (N=3) had minimal lipid deposition.

[0047] 3. Lipid profile of rat placental tissue like Figure 2 As shown, Oil Red O staining of the placenta tissue in the Rupp model group showed more lipid deposition ( P <0.001), the lipid deposition in the Sham group (N=6) was very small; the weight and size of the Rupp model mice (N=6) were significantly lower than those in the Sham group ( P <0.01).

[0048] 4. Lipid deposition in trophoblasts like Figure 3 As shown, the hypoxia group (N=3) had more lipid deposition in trophoblasts ( P <0.001). The lipid deposition in trophoblasts of the normal group (N=3) was very low.

[0049] 5. Changes in lipid metabolism indicators of trophoblasts like Figure 4 As shown, compared with normal trophoblasts (N=3), the mRNA expressions of fatty acid synthase (FASN) and fatty acid binding protein 4 (FABP4) in the hypoxia group (N=3) were significantly increased ( P <0.001), and the mRNA expressions of PPARγ and liver X receptor α (LXRα) were significantly decreased ( P <0.001), PPARγ mRNA expression was significantly decreased in placental tissues of PE patients (N=3) and Rupp model mice (N=3). In pregnant women's placental tissue, PPARr mRNA expression levels were not correlated with maternal weight.

[0050] 6. Exploration of the mechanism of action of PPARγ like Figure 5 As shown in Figure 2, RT-qPCR analysis showed that compared with HTR-8 / SVneo cells cultured normally, the expression of PPARγ mRNA in cells cultured under hypoxia was significantly decreased ( P<0.001). However, Western blot analysis revealed the opposite trend. Hypoxia treatment significantly increased the expression of total PPARγ protein and its phosphorylated form (p-PPARγ) in cells ( P <0.001).

[0051] 7. Trophoblast migration and invasion like Figure 6 As shown, compared with the hypoxia group, the migration and invasion abilities of trophoblasts in the Hypoxia+Rosiglitazone group were significantly enhanced ( P <0.001), the migration and invasion abilities of trophoblasts in the Hypoxia+T0070907 group were significantly weakened ( P <0.001).

[0052] 8. si-PPARγ transfection verification like Figure 7 As shown in the figure, fluorescence microscopy showed that 36 hours after transfection of si-PPARγ into HTR-8 / SVneo cells, strong green fluorescence was visible, and the transfection efficiency was greater than 80%. Western blot and RT-qPCR results showed that the relative expression of PPARγ in HTR-8 / SVneo cells was significantly decreased in the si-PPARγ group compared with the si-NC group ( P <0.001), the silencing effect was the most obvious.

[0053] 9. Effects of si-PPARγ on trophoblast migration and invasion under hypoxic conditions like Figure 8 As shown, compared with the Hypoxia group, the migration and invasion abilities of trophoblasts in the si-PPARγ group were significantly reduced ( P <0.001), the migration and invasion abilities of trophoblasts in the si-PPARγ+Rosiglitazone group did not recover ( P <0.001).

[0054] It should be noted that when numerical ranges are mentioned in the present invention, it should be understood that both endpoints of each numerical range and any value between the two endpoints may be selected. Since the steps and methods used are the same as those in the embodiments, in order to avoid redundancy, the present invention describes preferred embodiments. Although preferred embodiments of the present invention have been described, those skilled in the art may make additional changes and modifications to these embodiments once they understand the basic inventive concepts. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0055] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.

Claims

1. Use of a PPARγ agonist in the preparation of a drug for preventing, alleviating or treating preeclampsia.

2. The use according to claim 1, characterized in that The PPARγ agonist is used to enhance the migration ability of human chorionic trophoblast cells under hypoxic conditions.

3. The use according to claim 1, characterized in that The PPARγ agonist is used to enhance the invasion ability of human chorionic trophoblast cells under hypoxic conditions.

4. The use according to claim 2 or claim 3, characterized in that The human chorionic trophoblast cells are HTR-8 / SVneo.

5. The use according to claim 1, characterized in that The PPARγ agonist is rosiglitazone, GW1929, daglitazone, saikosaponin A or MBX-102 acid.

6. The use according to claim 1, characterized in that The dosage form of the medicine is an oral preparation.

7. A drug for preventing, alleviating or treating preeclampsia, characterized in that: The only effective active ingredient of the drug is the PPARγ agonist according to claim 1.

8. The drug according to claim 7, characterized in that The drug consists of a PPARγ agonist and a solvent.

9. The drug according to claim 7, characterized in that The PPARγ agonist is rosiglitazone; the concentration of rosiglitazone in the drug is 5mM~15mM.

10. The drug according to claim 7, characterized in that The solvent is DMSO.

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