The role of Ca2+ signalling and InsP3R in the pathogenesis of intrahepatic cholestasis of pregnancy.

Abstract

Background: In order to contribute new insights for future prevention and treatment of intrahepatic cholestasis of pregnancy (ICP), and to promote positive pregnancy outcomes, we evaluated serum Ca²⁺ levels and inositol 1,4,5-trisphosphate receptor (InsP3R) expression in the liver tissue of a rat ICP model.

Methods: After establishing the model by injection of oestradiol benzoate and progesterone into pregnant rats, animals were divided into normal control (n = 5) and ICP model groups (n = 5). The expression of InsP3R protein in the liver, and serum levels of Ca²⁺, glycocholic acid and bile acid were detected.

Results: InsP3R mRNA and protein were significantly lower in the ICP model group compared to the normal group, as determined by qPCR and immunohistochemistry, respectively. Serum enzyme-linked immunosorbent assay results revealed significantly higher levels of glycocholic acid and bile acid in the ICP model group compared to the normal group, while Ca²⁺ levels were significantly lower. The levers of Ca²⁺ were significantly and negatively correlated with the levels of glycocholic acid. The observed decrease in Ca²⁺ was associated with an increase in total bile acids, but there was no significant correlation.

Conclusions: Our results revealed that the expression of InsP3R and serum Ca²⁺ levels was significantly decreased in the liver tissue of ICP model rats. Additionally, Ca²⁺ levels were found to be negatively correlated with the level of glycocholic acid.