Effect of bile Acid on fetal lung in rat model of intrahepatic cholestasis of pregnancy

Abstract

Objective. To determine the correlation between maternal bile acid (BA) level and fetal pulmonary surfactant in rats and study the effects of BA on fetal lung in rat model of intrahepatic cholestasis of pregnancy. Methods. Forty pregnant rats were treated with (A) 5.5 mg/kg BA, (B) 1.4 mg/kg BA, and (C) 1 ml physiological saline. Levels of total bile acid (TBA), ALT, AST, TBIL, DBIL, and SP-A were determined and the lungs of fetal rats were analyzed for pathological changes. Results. Groups A and B intervened with BA showed significant higher level of TBA in both maternal and fetal serum, more mortality rate of fetal rats, more concentration of SP-A in fetal serum, and wider alveolus mesenchyme of fetal rats than the control Group C. Higher level of BA associated with increased fetal risk and lower numerical density of mitochondria in type II alveolar epithelial cells. The levels of TBA in maternal serum were found to have significant positive correlation with those in fetal serum and SP-A level but negatively with the area of alveolus and the numerical density of lamellar body. Conclusions. The TBA level in maternal serum showed significant association with lung pathological changes in fetal rats.

Figure 1

The morphology of fetal rat lungs in light microscope. (a) The high bile acid group: immature fetal lung tissue with smaller alveolar space, thicker alveolar septal, and a large number of hemorrhagic lesions were observed. HE: ×100 (A1), ×400 (A2). (b) The low bile acid group: fetal lung tissue with small alveolar space and thick alveolar septal were observed. HE: ×100 (B1), ×400 (B2). (c) The experimental control group: mature fetal lung tissue with large alveolar space and thin alveolar septal were observed. Alveolar epithelial cells, cytoplasm stained (red), and nuclear (flat). HE: ×100 (C1), ×400 (C2).

Figure 2

The morphology of fetal rat lungs in electronic microscope. (a) The high bile acid group: type II alveolar epithelial cells with swelling mitochondria were degenerated. Lamellar body had disappeared. A large number of red blood cells, proteins, cell debris falling, and edema fluid were filled in alveolar cavity. ×5000 (A1), ×12000 (A2). (b) The low bile acid group: type II alveolar epithelial cells with decreasing microvilli on the surfaces and slight swelling mitochondria were observed. ×5000 (B1), ×12000 (B2). (c) The experimental control group: type II alveolar epithelial cells were in good condition. A clear lamellar structure can be observed in lamellar bodies. ×5000 (C1), ×12000 (C2). Arrow A: swelled mitochondria (balloon-like); arrow B: lamellar body.