- Journal Information
- Archive
- Submission
- For Reviewers
- Statement and Policies
- 个人中心
- 退出登录
浏览全部资源
扫码关注微信
- Journal Information
- Archive
- Submission
- For Reviewers
- Statement and Policies
Improving effect and its mechanism of luteolin on placental dysfunction in rats with gestational diabetes mellitus
- ZHONGGUO YAOFANG Vol. 35, Issue 22, Pages: 2763-2768(2024)
- 作者机构：
1.南阳医学高等专科学校基础医学部，河南 南阳 473000
2.南阳医学高等专科学校第一附属医院产科，河南 南阳 473000
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2024.22.10
CLC： R965;R714.256Published：30 November 2024，
Received：17 April 2024，
Revised：20 August 2024，
- 稿件说明：
移动端阅览
胡殿鹏,张举,侯奕忻等.木犀草素对妊娠糖尿病大鼠胎盘功能障碍的改善作用及机制 Δ[J].中国药房,2024,35(22):2763-2768.
HU Dianpeng,ZHANG Ju,HOU Yixin,et al.Improving effect and its mechanism of luteolin on placental dysfunction in rats with gestational diabetes mellitus[J].ZHONGGUO YAOFANG,2024,35(22):2763-2768.
胡殿鹏,张举,侯奕忻等.木犀草素对妊娠糖尿病大鼠胎盘功能障碍的改善作用及机制 Δ[J].中国药房,2024,35(22):2763-2768. DOI： 10.6039/j.issn.1001-0408.2024.22.10.
HU Dianpeng,ZHANG Ju,HOU Yixin,et al.Improving effect and its mechanism of luteolin on placental dysfunction in rats with gestational diabetes mellitus[J].ZHONGGUO YAOFANG,2024,35(22):2763-2768. DOI： 10.6039/j.issn.1001-0408.2024.22.10.
摘要
目的
2
基于hedgehog（Hh）信号通路探讨木犀草素（Lut）对妊娠糖尿病（GDM）大鼠胎盘功能障碍的改善作用及潜在机制。
方法
2
随机选择雌鼠20只作为对照组，以正常饲料喂养。剩余雌鼠以高脂高糖饲料喂养8周后与雄性大鼠合笼，取妊娠大鼠，腹腔注射35 mg/kg的链脲佐菌素以构建GDM雌鼠模型；将造模成功的雌鼠随机分为模型组、SAG组（Hh信号通路激活剂SAG 50 mg/kg）、Lut低剂量组（Lut 40 mg/kg）、Lut高剂量组（Lut 80 mg/kg）、Lut高+ITR组（Lut 80 mg/kg+Hh信号通路拮抗剂伊曲唑康50 mg/kg），每组20只。各药物组雌鼠灌胃相应药液，每天1次，持续19 d。末次给药后，检测各组雌鼠的糖脂代谢参数（空腹血糖、空腹胰岛素水平和胰岛素抵抗指数）、胎盘质量和通透性[以伊文思蓝（EB）含量表示]，观察其胎盘组织病理变化，检测其胎盘组织中超氧化物歧化酶（SOD）活性及丙二醛（MDA）、还原型谷胱甘肽（GSH）含量以及Sonic Hh（Shh）、Patched-1（Ptch1）、Smoothened（Smo）、Gil家族锌指蛋白1（Gli1）的表达水平。
结果
2
与对照组相比，模型组大鼠胎盘组织中毛细血管管腔狭窄，血管周围可见纤维化区域；其糖脂代谢参数、胎盘质量、EB及MDA含量均显著升高，SOD活性、GSH含量及Shh、Ptch1、Smo、Gli1蛋白的表达水平均显著降低（
P
＜0.05）。与模型组相比，SAG组和Lut低、高剂量组大鼠胎盘组织中毛细血
管管腔变宽，血管周围纤维化明显减少；糖脂代谢参数、胎盘质量、EB及MDA含量均显著降低，SOD活性、GSH含量及Shh、Ptch1、Smo、Gli1蛋白的表达水平均显著升高（
P
＜0.05）；且Lut高剂量组上述参数与SAG组相比差异均无统计学意义（
P
＞0.05）。Hh信号通路拮抗剂伊曲唑康可显著逆转Lut对上述指标的改善作用（
P
＜0.05）。
结论
2
Lut可改善GDM大鼠的糖代谢参数，降低胎盘通透性，减轻其胎盘组织病理损伤和氧化应激，上述作用可能与激活Hh信号通路有关。
Abstract
OBJECTIVE
2
To explore the improving effect of luteolin （Lut） on placental dysfunction in rats with gestational diabetes mellitus （GDM） and its potential mechanism based on hedgehog （Hh） signaling pathway.
METHODS
2
Twenty female rats were randomly selected as a control group and fed a normal diet. The remaining female rats were fed a high-fat and high-sugar diet for 8 weeks and then caged with male rats. Pregnant rats were administered 35 mg/kg streptozotocin intraperitoneally to establish GDM models. Successfully modeled female rats were randomly allocated to model group， SAG group （Hh signaling pathway activator SAG 50 mg/kg）， Lut low-dose group （Lut 40 mg/kg）， Lut high-dose group （Lut 80 mg/kg）， and Lut high+ITR group （Lut 80 mg/kg+Hh signaling pathway antagonist itraconazole 50 mg/kg）， with 20 rats in each group. Female rats in each drug group were intubated with the corresponding drug solution once a day for 19 days. After the final administration， the serum glucose-fat metabolic parameters （levels of fasting blood glucose and fasting insulin， insulin resistance index）， placental quality， placental permeability [Evan’s blue （EB） content]， and pathological changes in placental tissue were observed. The activities of superoxide dismutase （SOD）， the contents of malondialdehyde （MDA） and reduced glutathione （GSH）， and the protein expressions of Sonic Hh （Shh）， Patched-1 （Ptch1）， Smoothened （Smo） and Gli family zinc finger-1 （Gli1） in placental tissue were detected.
RESULTS
2
Compared with the control group， rats in the model group showed narrow
capillary lumens， perivascular fibrosis in placental tissue， and a significant increase in serum glucose-fat metabolic parameters， placental quality， contents of EB and MDA， while there was a significant decrease in SOD activity， GSH content， and protein expressions of Shh， Ptch1， Smo and Gli1 （
P
＜0.05）. Compared with the model group， rats in the SAG group， Lut low-dose and high-dose groups had widened capillary lumens， a significant decrease in perivascular fibrosis in placental tissue， serum glucose-fat metabolic parameters， placental qualities， EB and MDA contents， while there was a significant increase in SOD activities， GSH contents， and protein expressions of Shh， Ptch1， Smo and Gli1 （
P
＜0.05）， with the high-dose group showing no significant difference compared to the SAG group （
P
＞0.05）. The Hh signaling pathway antagonist itraconazole could significantly reverse the improving effects of Lut on the above indicators （
P
＜0.05）.
CONCLUSIONS
2
Lut can improve glucose metabolism parameters of GDM rats， reduce placental permeability， alleviate pathological damage to placental tissue， and reduce oxidative stress. These effects may be related to the activation of the Hh signaling pathway.
关键词
木犀草素妊娠糖尿病胎盘功能障碍hedgehog信号通路
Keywords
gestational diabetes mellitusplacental dysfunctionhedgehog signaling pathway
references
SUN D G，TIAN S，ZHANG L，et al. The miRNA-29b is downregulated in placenta during gestational diabetes mellitus and may alter placenta development by regulating trophoblast migration and invasion through a HIF3A-dependent mechanism[J]. Front Endocrinol，2020，11：169.
MEYRUEIX L P，GHARAIBEH R，XUE J，et al. Gestational diabetes mellitus placentas exhibit epimutations at placental development genes[J]. Epigenetics，2022，17（13）：2157-2177.
QUEIROZ M，LEANDRO A，AZUL L，et al. Luteolin improves perivascular adipose tissue profile and vascular dysfunction in goto-kakizaki rats[J]. Int J Mol Sci，2021，22（24）：13671.
XIONG C，WU Q L，FANG M L，et al. Protective effects of luteolin on nephrotoxicity induced by long-term hyperglycaemia in rats[J]. J Int Med Res，2020，48（4）：300060520903642.
EDDY A C，RAJAKUMAR A，SPRADLEY F T，et al. Luteolin prevents TNF-α-induced NF-κB activation and ROS production in cultured human placental explants and endothelial cells[J]. Placenta，2024，145：65-71.
YAO Q Y，LIU J，XIAO L，et al. Sonic hedgehog signa-ling instigates high-fat diet-induced insulin resistance by targeting PPARγ stability[J]. J Biol Chem，2019，294（9）：3284-3293.
XIAO Q，ZHAO X Y，JIANG R C，et al. Increased expression of Sonic hedgehog restores diabetic endothelial progenitor cells and improves cardiac repair after acute myocardial infarction in diabetic mice[J]. Int J Mol Med，2019，44（3）：1091-1105.
FU S B，FU S Q，MA X N，et al. MiR-875-5p regulates IR and inflammation via targeting TXNRD1 in gestational diabetes rats[J]. Mol Med Rep，2021，23（5）：303.
NGUYEN V，CHAVALI M，LARPTHAVEESARP A，et al. Neuroprotective effects of Sonic hedgehog agonist SAG in a rat model of neonatal stroke[J]. Pediatr Res，2021，90（6）：1161-1170.
JOHANSSON H K L，TAXVIG C，OLSEN G P M，et al. Effects of the hedgehog signaling inhibitor itraconazole on developing rat ovaries[J]. Toxicol Sci，2021，182（1）：60-69.
SHI Y H，QIAN J，ZHANG F，et al. Low molecular weight heparin（nadroparin）improves placental permeabi-lity in rats with gestational diabetes mellitus via reduction of tight junction factors[J]. Mol Med Rep，2020，21（2）：623-630.
刘莹莹，赵一梅，杨夫艳，等. 妊娠糖尿病患者血清microRNA-873-5p、ZEB1与胰岛素抵抗、母婴结局的相关性研究[J]. 中国现代医学杂志，2023，33（11）：14-19.
LIU Y Y，ZHAO Y M，YANG F Y，et al. Correlation of serum microRNA-873-5p and ZEB1 levels with insulin resistance，maternal，and infant outcomes in patients with gestational diabetes mellitus[J]. China J Mod Med，2023，33（11）：14-19.
HUANG T T，SUN W J，LIU H Y，et al. p66Shc-mediated oxidative stress is involved in gestational diabetes mellitus[J]. World J Diabetes，2021，12（11）：1894-1907.
WANG H R，CHEN X Z，MIAO X Q，et al. Dendrobium mixture improves gestational diabetes mellitus through regulating Nrf2/HO1 signaling pathway[J]. Biomed Pharmacother，2022，155：113656.
ZHANG L W，FU X J，NI L，et al. Hedgehog signaling controls bone homeostasis by regulating osteogenic/adipogenic fate of skeletal stem/progenitor cells in mice[J]. J Bone Miner Res，2022，37（3）：559-576.
SU Y Z，XING H，KANG J，et al. Role of the hedgehog signaling pathway in rheumatic diseases：an overview[J]. Front Immunol，2022，13：940455.
HAN X，LI B. The emerging role of noncoding RNAs in the hedgehog signaling pathway in cancer[J]. Biomed Pharmacother，2022，154：113581.
XU A R，FAN Y Y，LIU S，et al. GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway[J]. J Ovarian Res，2022，15（1）：141.
0
Views
0
下载量
0
CSCD
- L-PDFDownload
- WORDDownload
- Meta-XMLDownload
- BibTeXDownload
- EndnoteDownload
- RefMan Download
- NoteExpressDownload
- NoteFirstDownload
Publicity Resources
Related Articles
Related Author
Related Institution
- Address：8th Floor, Sihuan Building, No. 129 Daping Main Street, Yuzhong District, Chongqing, China Postal code：400042
- Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号
公网安备50010302001817 - It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
- Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.