Effect of 25-hydroxyvitamin D 3-loaded polylactic acid microspheres on myocardial injury in rats with gestational diabetes mellitus through NLRP3/Caspase-1/GSDMD signaling axis
10.3760/cma.j.cn121382-20240310-00403
- VernacularTitle:25-羟基维生素D 3聚乳酸微球通过NLRP3/ Caspase-1/GSDMD信号轴对妊娠期糖尿病大鼠心肌损伤的影响
- Author:
Ting YIN
1
;
Bufei WANG
;
Wushan LI
Author Information
1. 济南市妇幼保健院产科，济南 250001
- Keywords:
Gestational diabetes mellitus;
25-Hydroxyvitamin D 3;
Polylactic acid microspheres;
Myocardial injury
- From:
International Journal of Biomedical Engineering
2024;47(4):318-324
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of 25-hydroxyvitamin D 3-loaded polylactic acid microspheres on myocardial injury in rats with gestational diabetes mellitus as well as its regulatory effects on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3)-cysteinyl aspartate specific proteinase-1 (Caspase-1)-gasdermin D (GSDMD) signaling axis. Methods:25-Hydroxyvitamin D 3-loaded polylactic acid microspheres were prepared by W/O emulsification and solvent volatilization method. The morphology of the microspheres was observed by scanning electron microscope, the diameters of the microspheres were detected by laser particle size analyzer, and the cumulative release rate was calculated. Pregnant rats were injected intraperitoneally with streptozotocin to establish a rat model of gestational diabetes mellitus and were randomly divided into the model group, the control group, and the microsphere group, with 10 rats in each group. Another 10 pregnant rats were taken as the sham operation group. In the microsphere group, a total of 100 μl of microsphere suspension was injected at 4 points along the edge of the left ventricle, while the control group was injected with an equal amount of blank microspheres in the same way, and the sham operation group and the model group were injected with an equal amount of physiological saline in the same way. Samples were taken at 21 d of gestation for subsequent experiments. Fasting blood glucose (FBG), fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) of the rat model were detected. Cardiac troponin I (cTnI) and serum creatine kinase isoenzyme (CK-MB) levels were detected by a fully automated biochemical analyzer. Interleukin (IL)-1β and tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, and malondialdehyde levels in myocardial tissues were detected by enzyme-linked immunosorbent assay (ELISA). Protein expression of NLRP3, Caspase-1 and GSDMD was detected by Western Blot. Results:The scanning electron microscope observation showed that the microspheres were regular spherical with uniform size, compact surface and no cracks. The diameter of the microspheres was (13.48 ± 2.04) μm, and the particle size distribution was concentrated and homogeneous. The release of 25-hydroxyvitamin D 3-loaded polylactic acid microspheres was slow in the first 5 days, and then the cumulative release rate increased significantly, and the cumulative release rate reached more than 80% on the 28th day, and then stabilized. Compared with the sham operation group, the levels of FBG, HOMA-IR, cTnI, CK-MB, IL-1β, TNF-α, malondialdehyde as well as the protein expression of NLRP3, Caspase-1 and GSDMD were increased in the model group, and the activities of FINS, SOD and GSH-Px were decreased (all P < 0.05). Compared with the model and control groups, the levels of FBG, HOMA-IR, cTnI, CK-MB, IL-1β, TNF-α, malondialdehyde, and protein expression of NLRP3, Caspase-1, and GSDMD were decreased in the microsphere group, and the activities of FINS, SOD, and GSH-Px were increased (all P < 0.05). Conclusions:The 25-hydroxyvitamin D 3-loaded polylactic acid microspheres can reduce blood glucose level and insulin resistance, reduce myocardial inflammation and oxidative stress injury, and alleviate myocardial injury in rats with gestational diabetes mellitus, possibly by inhibiting the NLRP3/Caspase-1/GSDMD signaling axis.
