Improving effect and its mechanism of luteolin on placental dysfunction in rats with gestational diabetes mellitus
- VernacularTitle: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
- Author:
Dianpeng HU
1
;
Ju ZHANG
2
;
Yixin HOU
1
;
Lin CHENG
1
;
Jialu LU
1
Author Information
1. Dept. of Basic Medicine，Nanyang Medical College，Nanyang Henan 473000，China
2. Dept. of Obstetrics，the First Affiliated Hospital of Nanyang Medical College，Nanyang Henan 473000，China
- Publication Type:Journal Article
- Keywords:
luteolin;
gestational diabetes mellitus;
placental dysfunction;
hedgehog signaling pathway
- From:
China Pharmacy
2024;35(22):2763-2768
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE 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 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. HBB_ RESULTS 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 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.
