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Objective To investigate the impact of high bile acid levels of pregnant mice on the morphology and function of the fetal rat brain. Explore the differences in the levels of different bile acid concentrations in fetal rat serum neuron-specific enolase (neuron specific enolase, NSE) and its relationship with the serum bile acid concentration. The 30 clean adult pregnancy SD rats were randomly divided into three groups A, B, C, n = 10. A group of pregnant rats in the pregnancy 13 to 20 days, once daily intraperitoneal injection of pure bile acid 5.5 mg · kg -1 · d > -1 (high acid group) ; B group of pregnant rats once daily intraperitoneal injection of pure bile acid 1.4mg · kg -1 · d > -1 (low acid group); C group (control group) synchronization injected with normal saline. 21 days of pregnancy Caesarean section fetus, determination of fetal weight and mortality. The collected blood samples of pregnant mice and fetal rat determination of the concentration of total bile acid (TBA), and blood samples from the same batch of fetal rat measured by ELISA serum neuron-specific enolase (neuron-specific enolase, NSE) level. Meanwhile, the fetal rat brains were removed, fetal rat brain pathological changes of light and electron microscopy. Results 1. Pregnant mice serum ALT, AST, TBIL, DBIL concentration before intervention groups showed no significant difference (P> 0.05). Intervention after the pregnant mouse serum ALT, AST, TBIL DBIL level in Group A was significantly higher than that in group C, the more significant difference, P> 0.05; A group, C group and B group showed no significant difference, P> 0.05. Pregnant mouse serum TBA concentration in groups A, B, C pairwise comparison showed a significant difference, P <0.01. 2. The three groups of pregnant mice and fetal rat serum TBA concentrations were in group A (22.32 ± 8.12) μmol / L, (28.84 ± 8.06) μmol / L; B group (9.77 ± 3.56) μmol / L (9.34 ± 3.55) μool / L; C group (3.60 ± 1.78) μmol / L (3.95 ± 1.19) μumol / L,. Between the two groups showed significant differences (P <0.01). Pregnant mice serum the TBA and fetal serum TBA concentration was positively correlated with r = 0.875. The fetal rat stillbirth rate in the three groups, A, B, C are 30.10%, 16.85% and 7.06%, respectively, between two groups were significantly different, P <0.05. The average weight of fetal rats in the three groups, A, B, C, respectively (4.24 ± 0.98) g, (5.82 ± 0.32) g and (6.14 ± 0.77) g, A group than in the group B and group C, more significant differences P <0.05; B and C groups showed no significant difference, P> 0.05 4. The three groups of fetal rat serum NSE concentration, respectively, in the three groups, A, B, C (31.90 ± 13.12) ng / ml (13.91 ± 5.85) ng / ml and (9.33 ± 3.94) ng / ml, A group was significantly higher than that group B and group C, P <0.01; A group and B group showed no significant difference (P> 0.05). Fetal rat serum NSE TBA concentration showed a positive correlation r = 0.758 5. Fetal rat cerebral cortex tissue optical microscope, the pathological changes: the cerebral cortex tissue levels of disorder, neuronal degeneration and necrosis, the density decreases, the nucleus pyknosis. The neuronal degeneration area in three groups, A, B, C, respectively (1.38 ± 0.58), (1.48 ± 0.66) and (0.72 ± 0.30) in group A and group B was significantly higher than that in group C, P <0.01 ; A group and B group showed no significant difference (P> 0.05). Fetal rat neuronal degeneration area integral fetal rat serum NSE concentration correlation coefficient of 0.282. The neuronal necrosis area in three groups, A, B, C, respectively (1.84 ± 0.73), (0.86 ± 0.38) and (0.58 ± 0.27), the A group was significantly higher than that in group B and group C, P < 0.05; B group and C group no significant difference (P> 0.05). The neuronal necrosis area with fetal rat serum NSE concentration was a positive correlation r = 0.798 6. Transmission electron microscopy of fetal rat parietal cortex change: fuzzy neural nuclear membrane bilayer structure, nuclear condensation nucleoli disappear, chromatin condensation; significantly reduced the number of the endoplasmic reticulum and mitochondria, the residual mitochondrial swelling destruction, crest cavitation disappeared. The three groups of fetal rat brain cortex mitochondria number density (Nv), respectively, in the three groups, A, B, C (21.92 ± 9.00) μm -3 , (45.48 ± 13.12) μm - 3 and (36.13 ± 12.13) μm -3 . A group was significantly lower than that in group B and group C, P <0.01; B and C groups showed no significant difference (P> 0.05). Fetal rat brain cortex mitochondrial average volume ((?)) In the three groups A, B, C, respectively (7.01 ± 1.79) × 10 -4 μm 3 , (5.66 ± 1.57) × 10 -4 μm 3 and (3.15 ± 1.21) × 10 -4 μm 3 . Group A and Group B was significantly higher than the C group, P <0.01; B and C groups showed no significant difference, P> 0.05. Conclusion cholic fetal rat brain tissue can be significant pathological changes, the low concentration of bile acids cause nerve cell degeneration and mitochondrial volume increases, the high concentration of bile acid group led to a decrease in the number of the nerve cell necrosis and mitochondria. The positive correlation of fetal rat serum NSE and concentration, TBA.
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