Objective To investigate the clinical correlation between gestational diabetes mellitus (GDM) and the NLRP3-ASC-Caspase-1-IL-1β/IL-18-TGF-β signaling pathway of cell pyroptosis.
Methods A total of 80 GDM undergoing gestational examination patients were selected as the study subjects, including 60 GDM patients who were not treated with insulin during pregnancy (GDM group without insulin treatment) and 20 GDM patients who were treated with insulin (GDM group with insulin treatment). In the same period, 30 healthy pregnant women were included as control group. Age, gestational age, body mass index (BMI), fasting blood glucose (FPG), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were compared in all groups. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 mRNA in peripheral blood mononuclear cells (PBMCs) of pregnant women in each group, and protein expression levels were detected by Western blot. Enzyme-linked immunosorbent assay (ELISA) was used to determine the expression levels of interleukin-1β (IL-1β), interleukin-18 (IL-18) and transforming growth factor-β (TGF-β) in the serum of patients in eachgroup. Spearman's correlation analysis was used to analyze the related factors affecting GDM occurrence.
Results The mRNA expression levels of NLRP3, ASC and Caspase-1 in PBMCs of the GDM patients (GDM group without insulin treatment and GDM group with insulin treatment) showed significant difference compared with those of control group (P < 0.05); the mRNA expression levels of NLRP3, ASC and Caspase-1 in PBMCs of the GDM group treated with insulin showed no significant difference compared with those of the GDM group treated without insulin (P > 0.05). NLRP3 mRNA was positively correlated with FPG in the GDM group treated with insulin(P < 0.05); the ASC mRNA was positively correlated with HbA1c in the GDM group without insulin treatment, and positively correlated with HbA1c and TG in the GDM group with insulin treatment (P < 0.05). Caspase-1 mRNA was positively correlated with FPG in the control group, positively correlated with BMI in the GDM group without insulin treatment, and positively correlated with BMI and TC in the GDM group with insulin treatment (P < 0.05). The expression levels of NLRP3, ASC and Caspase-1 protein in PBMCs and serum levels of IL-1β, IL-18 and TGF-β among the three groups showed significant differences (P < 0.05). ASC was positively correlated with FPG and HbA1c in the GDM group without insulin treatment, and positively correlated with FPG, TC, IL-1β and IL-18 in the GDM group with insulin treatment (P < 0.05). Caspase-1 was positively correlated with FPG in control group, and positively correlated with FPG, HbA1c, LDL-C and IL-1β in the GDM group without insulin treatment (P < 0.05). Caspase-1 was positively correlated with FPG, HbA1c, LDL-C and IL-1β in the GDM group with insulin treatment (P < 0.05).
Conclusion The pyroptosis associated NLRP3-ASC-Caspase-1-IL-1β/IL-18-TGF-β signaling pathway centered on the NLRP3 inflammasome may play an important role in the occurrence and development of GDM.
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