[Effects of high cholic acid on fetal brains of pregnant rats].
OBJECTIVE
To investigate the effects of morphous on fetal brains in pregnant rat of high cholic acid.


METHODS
Randomly deviding 30 SD pregnant rats to three groups A, B and C, every group is 10. From 13th to 20th days of pregnancy, injecting 5.5 mg x kg(-1) x d(-1) cholic acid to pregnant rats of group A, 1.4 mg x kg(-1) x d(-1) cholic acid to group B and the partes aequales normal saline to group C by intraperitoneal injection one time every day. In the 21st day of pregancy, to cut the belly open and take the fetus out and record the total fetus, live fetus and the weight. Determine the serum concentration of total bile acid (TBA) in pregnant rats and fetal rats. Enzyme linked immunosorbent assay(ELISA) was used to detect the serum level of neuron-specific enolase (NSE) in fetal rats. Fix and embed the brain after decapitation, then to observe the pathological change of the fetal cerebrum under light microscope and electron microscope.


RESULTS
(1) The serum concentration of TBA of pregnant rats and fetal rats in group A is (22.3 +/- 8.1) micromol/L and (28.8 +/- 8.1) micromol/L, in group B is (9.8 +/- 3.6) micromol/L and (9.3 +/- 3.5) micromol/L, in group C is (3.6 +/- 1.8) micromol/L and (4.0 +/- 1.2) micromol/L. There is significant defference in every two groups, P < 0.01. The serum concentration of TBA between pregnant rats and fetal rats were positively correlated with each other, (r = 0.875, P < 0.01). (2) The mortinatality of fetus in group A, B and C are 30.1%, 16.9% and 7.1%, there is significant defference in every two groups, P < 0.05. (3) The serum lever of NSE of fetus in group A was significantly higher than that of group B and C, [(31.9 +/- 13.1) ng/L vs. (13.9 +/- 5.9) ng/L and (9.3 +/- 3.9) ng/L, both are P < 0.05]. But there is no significant difference between group B and C, P > 0.05. The serum level of TBA and NSE in fetus were positively correlated with each other, (r = 0.758, P < 0.01). (4) By the light microscope we found that the neuronal degeneration and necrosis. The level of organization disorder, the density of nerve cells decrease and the cell nucleus pyknosis and anachromasis. The neuronal degeneration area in group A and B are significantly higher than group C[(1.4 +/- 0.6) and (1.5 +/- 0.7) vs. (0.7 +/- 0.3), both are P < 0.05]. But there is no significant difference between group A and B, P > 0.05. The is no apparente correlation between the neuronal degeneration area and the serum level of NSE in fetus, r = 0.282, P > 0.05. The neuronal necrosis area in group A are significantly higher than group B and C [(1.8 +/- 0.7) vs. (0.9 +/- 0.4) and (0.6 +/- 0.3), both are P < 0.05]. But there is no significant defference between group B and C, P > 0.05. The neuronal necrosis area and the level of NSE in fetus were positively correlated with each other, r = 0.798, P < 0.01. (5) Under the electron microscope we found that the neuronal nuclear membrance ambiguity, karyopycnosis, nucleolus disappeared, nuclear chromatin rarefaction. The number of endoplasmic reticulum and mitochondria decrease, the residual mitochondria swelling, cristae quassation. The number density of mitochondria of nerve cells in group A is significantly lower than that of group B and C [(21.9 +/- 9.0) microm(-3) vs. (45.5 +/- 13.1) microm(-3) and (36.1 +/- 12.1) mcirom(-3), both are P < 0.01]. But there is no significant difference between group B and C, P > 0. 05. The volume of mitochondria of nerve cells in group A and B are significantly higher than that of group C [7.0 +/-1.8) x 10(-4) microm3 and (5.7 +/- 1.6) x 10(-4) microM3 vs. (3.2 +/- 1.2) x 10(-4) microm(3), both are P < 0.01]. But there is no significant difference between group A and B (P > 0.05).


CONCLUSIONS
There is apparente pathological change of fetal rats brain in cholic acid groups, the neuronal degeneration and the mitochondria swelling was mainly found in low cholic acid group, the neuronal necrosis and the mitochondria decrease was mainly found in high cholic acid group. The serum concentration of TBA and NSE in fetal rats were positively correlated with each other.
Tan
Li
L
Department of Obstetrics and Gynecology, Xiangya Second Hospital, Central South University, Changsha 410011, China.
Ding
Yi-ling
YL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D019826:Cholic Acid / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D020073:Gravidity; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D010751:Phosphopyruvate Hydratase; D019826:Cholic Acid