1.Mechanism of Bushen Huoxue Formula in regulating endometrial oxidative stress and fibrosis.
Si-Si TANG ; Rong CHEN ; Qian-Qian SONG
China Journal of Chinese Materia Medica 2025;50(1):218-236
Intrauterine adhesion(IUA) is a common gynecological disease that is difficult to treat, and there is a lack of specific effective drugs and measures to prevent endometrial fibrosis. In this study, the mechanism of endometrial oxidative stress and fibrosis regulation was studied in an IUA rat model constructed by Bushen Huoxue Formula intervention of mechanical injury combined with infection. A total of 72 SPF SD female rats aged 8-10 weeks were randomly divided into blank control group, model control group, low-dose, medium-dose, and high-dose groups of Bushen Huoxue Formula, and estrogen groups. The rats in the estrous cycle of the model control group and the positive control group were simulated with surgical injury and infection, and the sham operation group was treated with on-off abdominal treatment. After successful modeling, the model control group was administered intragastrically with purified water of 15 μL·g~(-1) every day. The low-dose group was administered intragastrically with Bushen Huoxue Formula of 7.8 g·kg~(-1); the medium-dose group was administered intragastrically with Bushen Huoxue Formula of 15.6 g·kg~(-1), and the high-dose group was administered intragastrically with Bushen Huoxue Formula of 31.2 g·kg~(-1). The estrogen group was administered intragastrically with estradiol valerate of 4.2 mg·kg~(-1). After continuous intervention for 28 days, all rats were deprived of water and killed to collect blood and tissue. Hematoxylin-eosin(HE) staining calculated the number of uterine glands; Masson staining calculated the area of uterine collagen fibers. Combined with HE and Masson staining, semi-quantitative scores were performed on the degree of endometrial fibrosis. Immunohistochemistry was performed to detect the vascular endothelial growth factor(VEGF), stromal cell-derived factor-1(SDF-1), and transforming growth factor-β1(TGF-β1) expression in rats' uterine tissue. Enzyme-linked immunosorbent assay(ELISA) dected angiopoietin 1(IFN-γ), interleukin-1α(IL-1α), TGF-β1, tumor necrosis factor-α(TNF-α), collagen type Ⅳ(Ⅳ-Col), leukemia inhibitory factor(LIF), superoxide dismutase(SOD)、glutathione peroxidase(GSH-Px);The mRNA expressions of Smad2, Smad3, adisintegrin and metalloproteinase(ADAM17) and TGF-β1 were determined by qPCR. Notch and ADAM17 protein expression in rat uterus were determined by Western blot. The results showed that the area of uterine fibrosis was significantly reduced and the conditions of edema and adhesion were effectively alleviated after high-dose intervention of Bushen Huoxue Formula. The levels of inflammatory factors and Ⅳ-Col were significantly decreased, and the levels of LIF and antioxidant enzymes were significantly increased. The mRNA expressions of Smad2, Smad3, ADAM17 and TGF-β1 were significantly down-regulated. Immunohistochemical results showed that Bushen Huoxu Formula could effectively increase the positive expression of SDF-1 and reduce the positive expression of VEGF and TGF-β1. Western blot results showed that the protein expressions of Notch and ADAM17 in high-dose, medium-dose and low-dose of Bushen Huoxu Formula groups were significantly down-regulated in a dose-dependent manner. These results suggest that Bushen Huoxue Formula may inhibit fibrosis process through ADAM17/Notch signaling pathway, suggesting that Bushen Huoxuet Formula is one of the potential therapeutic methods for IUA.
Animals
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Female
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Drugs, Chinese Herbal/administration & dosage*
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Rats, Sprague-Dawley
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Endometrium/pathology*
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Rats
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Fibrosis/metabolism*
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Oxidative Stress/drug effects*
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Humans
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Uterine Diseases/genetics*
;
Vascular Endothelial Growth Factor A/genetics*
2.Association of genetic polymorphism in plasminogen activator inhibitor-1 gene with endometrial hypoplasia in infertile women.
Jing-hua SUN ; Li -xue GUAN ; Dong-ju LIN ; Pei-feng DAI ; Li PAN ; Qian MU
Chinese Journal of Medical Genetics 2008;25(4):462-464
OBJECTIVETo investigate the relationship between the plasminogen activator inhibitor (PAI-1) polymorphisms and endometrial hypoplasia in infertile women.
METHODSThe study was conducted in 105 primary infertile patients with endometrial hypoplasia diagnosed by pathology and the thickness of endometrium by B-mode ultrasound and 85 controls who were not pregnant and had normal fertility. The -675 4G/5G polymorphism in the PAI-1 gene was detected by polymerase chain reaction-restriction fragment length polymerphim analysis.
RESULTSThe frequencies of 4G/4G genotype and 4G allele of the PAI-1 gene were higher in the patient group (48.6% and 66.2%) than in the normal controls (22.4% and 47.1%) (P < 0.01). ThePAI-1 4G/4G genotype was significantly associated with endometrial hypoplasia in the infertile patients (OR=4.9, 95% CI: 2.10-10.12).
CONCLUSIONThe present findings suggest that the 4G/5G polymorphism of the PAI-1 gene was associated with endometrial hypoplasia in infertile patients.
Adult ; Female ; Humans ; Infertility ; genetics ; Plasminogen Activator Inhibitor 1 ; genetics ; Polymorphism, Genetic ; Pregnancy ; Uterine Diseases ; genetics ; Women's Health
3.Clinical evaluation of the xMAP technology in detection of high-risk human papillomavirus.
Guang-dong LIAO ; Xiao-yan ZHANG ; Yu-hua GAO ; Bin LIU ; Xia LIU ; Lian-kun LI ; Feng CHEN ; Mei-lu BIAN ; Wen CHEN ; You-lin QIAO
Acta Academiae Medicinae Sinicae 2007;29(5):603-607
OBJECTIVETo evaluate the clinical application value of flexible multi-analyte profiling (xMAP) technology in detecting high-risk human papillomavirus (HR-HPV).
METHODSTotally 1 061 women, aged 21-65 years, were randomly enrolled into the study. Cervical exfoliated cells were used in xMAP technology and hybrid capture II (hc2). Pathological diagnosis was used as golden standard. Consistency of these two methods was assessed.
RESULTSThe sensitivity and specificity of xMAP technology were 80.31% and 85.83%, respectively. The positive and negative predictive values were 44.5% and 96.9%, respectively. The Kappa value for consistency between xMAP technology and hc2 was 0.58.
CONCLUSIONSThe specificity of xMAP technology is similar to hc2 test, but the sensitivity is inferior to hc2. However, these two methods show good consistency in the detection of HR-HPV.
Adult ; Aged ; Cervix Uteri ; virology ; Female ; Humans ; Middle Aged ; Papillomaviridae ; classification ; genetics ; isolation & purification ; Papillomavirus Infections ; diagnosis ; virology ; Sensitivity and Specificity ; Uterine Cervical Diseases ; diagnosis ; virology ; Virology ; methods ; Young Adult
4.Comparative proteome analysis of human papillomavirus-infected cervical specimens and the difference between the high- and low-risk genotypes of human papillomavirus.
Shu-zhen QI ; Guo-cheng ZHANG ; Jin-ping ZHANG ; Xue-si ZENG ; Yuan-hua CAO ; Ming-ying ZHONG ; Xiao-hua TAO ; Tong-yun LIU ; Qian-qiu WANG ; Rong-ge YANG
Acta Academiae Medicinae Sinicae 2007;29(5):597-602
OBJECTIVETo perform an comparative proteome analysis of human papillomavirus-infected cervical specimens and to investigate different expressions between high- and low-risk genotypes.
METHODSThe cervical specimens were divided into two groups (cervical intraepithelial neoplasia group and condyloma acuminatum group) according to their genotypes. Using comparative proteome technology, high-risk human papillomavirus-infected cervical intraepithelial neoplasia, low-risk human papillomavirus-infected condyloma acuminatum, and normal cervical intraepithelial tissue were compared. The differential expression protein spots were identified by mass spectrometry.
RESULTSTotally 26 differential spots were selected and analyzed, and 22 peptide mass fingerprints (PMF) maps were obtained by MALDI-TOF-MS. Eighteen proteins were preliminarily identified after searching the NCBInr database. The function information of these 18 proteins mainly involved cell metabolism, signal transduction, cell secretion, cell cytoskeleton construction, cell proliferation, and apoptosis.
CONCLUSIONThe proteomic expressions after the cervical infection of high- or low-risk genotype of human papillomavirus are obviously different.
Cervical Intraepithelial Neoplasia ; metabolism ; virology ; Cervix Uteri ; metabolism ; Condylomata Acuminata ; metabolism ; virology ; Female ; Genotype ; Humans ; Papillomaviridae ; genetics ; pathogenicity ; Papillomavirus Infections ; metabolism ; virology ; Proteome ; metabolism ; Risk ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Uterine Cervical Diseases ; metabolism ; virology
5.Association between human papillomavirus (HPV) type 16 infection and E6/E7 gene variant and the cervical lesions in Beijing.
Ying-jie YANG ; Jian ZHAO ; Qin-ping LIAO
Chinese Journal of Experimental and Clinical Virology 2007;21(1):32-34
OBJECTIVETo investigate the association between HPV16 infection, E6/E7 variations and the cervical lesions.
METHODSHPV subtypes were detected by using flow-through hybridization technique, E6/E7 gene was extracted from cervical lesions in 80 patients with HPV16 infection, PCR amplified, cloned into plasmid pMD18-T and sequenced.
RESULTSHPV 16 was the most common type which accounted for 33.3% (154/463), the HPV16 infection rates increased with the severity of cervical lesions (P < 0.05). Totally in 72 cases the complete E6 and E7 regions were successfully sequenced, the DNA mutation rate of E6/E7 was 88.9% (64/72). A mutation, E6-D32E (T96G) coincided with a specific type of E7 mutation, N29S (A86G). D32E/N29S mutation rate was 38.9% (28/72), the detection rate increased with the severity of cervical lesions (P < 0.05).
CONCLUSIONHPV 16 was the most common type in women with cervical lesions in Beijing, D32E/N29S variant associated with the cervical lesions.
Adult ; Aged ; China ; epidemiology ; Female ; Gene Frequency ; Genotype ; Host-Pathogen Interactions ; Human papillomavirus 16 ; genetics ; physiology ; Humans ; Middle Aged ; Mutation ; Oncogene Proteins, Viral ; genetics ; Papillomavirus E7 Proteins ; Papillomavirus Infections ; epidemiology ; pathology ; virology ; Repressor Proteins ; genetics ; Severity of Illness Index ; Uterine Cervical Diseases ; epidemiology ; pathology ; virology ; Uterine Cervical Neoplasms ; epidemiology ; pathology ; virology ; Young Adult
6.Effects of Jiantaiye on estrogen receptor and mRNA expressions in uterus of mice with embryo implantation dysfunction.
Yan-juan LIU ; Guang-ying HUANG ; Ming-wei YANG ; Ping GONG ; Ming-min ZHANG ; Fu-er LU
Chinese journal of integrative medicine 2005;11(1):41-44
OBJECTIVETo explore the effect of Jiantaiye (JTY) on the expression of estrogen receptor (ER) and ER mRNA in uterus of mice with embryo implantation dysfunction.
METHODSEmbryo implantation dysfunction mouse models were induced with mifepristone and treated with JTY. All animals were sacrificed on day 8 of pregnancy. The endometrial ER and ER mRNA expressions were assessed by immunnohistochemical SP method and semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR).
RESULTSArea ratio and absorbency of ER in the JTY treated group's gland and stroma were higher than those of the model group, quite similar to those of the normal control's, and ER mRNA expression in treated group's uterus was significantly higher than that in the models, but it was not significantly different from the normal control.
CONCLUSIONJTY improves the endometrial development by increasing ER and ER mRNA expressions of uterus of mice with embryo implantation dysfunction.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Embryo Implantation ; Endometrium ; drug effects ; metabolism ; Female ; Immunohistochemistry ; methods ; Male ; Mice ; Mice, Inbred Strains ; Pregnancy ; RNA, Messenger ; metabolism ; Receptors, Estrogen ; genetics ; metabolism ; Staining and Labeling ; Tissue Distribution ; Uterine Diseases ; immunology ; physiopathology ; Uterus ; drug effects ; immunology

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