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Objective: To explore the expression and clinical significance of constitutive androstane receptor (CAR) in placenta syntrophoblast from patients with intrahepatic cholestasis of pregnancy (ICP)., Methods: Placenta were collected from women with ICP who delivered from April 2009 to March 2010 in First Affiliated Hospital of Chongqing Medical University. According to the severity of ICP, patients were classified into mild ICP group (n = 10) and severe ICP group (n = 10). Ten healthy pregnant women who delivered in the same period were chosen as control group. The location of CAR protein in placenta was studied by immunohistochemical streptavidin-biotin complex (SABC) method. CAR mRNA level was determined by reverse transcription (RT)-PCR technique and CAR protein expression level was determined by western blot., Results: (1) CAR was located in the placenta syncytiotrophoblastic cells in control group and mild ICP group, showed light tan when stained, and was mainly in the cytoplasm. In severe ICP group, CAR was also located in placenta syncytiotrophoblastic cells but mainly in the nucleolus, showed dark tan when stained. (2) The mRNA expressions of CAR in control group, mild ICP group, severe ICP group were 0.06 ± 0.03, 0.07 ± 0.03 and 0.56 ± 0.03, respectively. CAR in severe ICP group was significantly higher than those in control group and mild ICP group (P < 0.05). The difference of mRNA between control group and mild ICP group was not statistically significant (P > 0.05). (3) The CAR protein levels in control group, mild ICP group, severe ICP group were 0.74 ± 0.03, 0.79 ± 0.03 and 1.02 ± 0.04, respectively. CAR protein expression in the severe ICP group was significantly higher than the other two groups (P < 0.05). And there was no statistical significance between mild group and control group (P > 0.05)., Conclusion: In ICP women, especially severe ICP patients, the CAR expression in placenta syncytiotrophoblastic cells increased appreciably, which may be involved in the maintenance of placenta barrier function and protection in ICP pathogenesis.

Objective: To evaluate the effects of different types of nitric oxide synthase (NOS) inhibitors on cerebral mitochondrial structure and function in fetal rats with intrauterine distress., Methods: Rats were divided into control group, acute ischemia group, treatment group 1 injection of [N omega-nitro-L-arginine (L-NNA) 4 mg/kg into pregnant rats' abdomen before ischemia], reperfusion group, treatment group 2 [injection of L-NNA 4 mg/kg into pregnant rats' abdomen before ischemia followed by injection of aminoguanidine (AG) 500 mg/kg before operation]. Changes of mitochondrial structure were observed by transmission electron microscopy and expression of neuronal nitric oxide synthase (nNOS) mRNA(A) through RT-PCR. Inducible nitric oxide synthase (iNOS) activity and mitochondrial Na(+)K(+)-ATPase and cytochrome oxidase activity were measured., Results: (1) The A of NOS (5 min, 15 min) in acute ischemia group was higher than that of treatment group 1 (P < 0.05). There was no difference between the A of nNOS (30 min) in two groups (P > 0.05). But the A of nNOS in two groups was higher than that in control group (P < 0.05). (2) iNOS activities in reperfusion group were all higher than those in treatment group 2. Both of those in two groups were higher than that in control group (P < 0.05). (3) Mitochondrial Rsv (5 min, 15 min) in acute ischemia group was smaller than those of treatment group 1 (P < 0.05). There was no difference between mitochondrial Rsv (30 min) in two groups (P > 0.05). Mitochondrial Rsv in reperfusion group was all smaller than those in treatment group 2. And mitochondrial Rsv in all the groups was smaller than that in control group (P < 0.05). (4) Na(+)K(+)-ATPase activity in treatment group 2 was higher than those in reperfusion group (P < 0.05). Na(+)K(+)-ATPase activity in two groups was lower than that in control group (P < 0.05)., Conclusions: nNOS and iNOS play a role in cerebral mitochondrial structure and function damage in fetal rats with intrauterine distress. L-NNA has some limited treatment effect on mitochondrial damage when intrauterine distress induces acute fetal hypoxic-ischemic brain damage. AG plays an obvious treatment role in mitochondrial damage during reperfusion following ischemia.

Objective: This study was to evaluate the grading of intrahepatic cholestasis of pregnancy (ICP)., Methods: All 278 ICP cases were collected in the First Affiliated Hospital of Chongqing Medical University between Jan 1999 and May 2003. They were graded into mild ICP and severe ICP based on liver function test. Outcome of pregnancy and perinatal mortality were assessed., Results: One hundred and ninety two cases were diagnosed as mild ICP while 86 cases were as severe ICP. There was significant difference in the average time of expectant therapy (10.3 +/- 4.8 vs 19.1 +/- 6.4 days) and gestational weeks (35.8 +/- 1.6 vs 37.7 +/- 1.9) between severe ICP and mild ICP groups (P < 0.01 and P < 0.001). The incidences of meconium passage, newborn asphyxia and admissions to neonatal intensive care unit in severe ICP were significantly higher than that in mild ICP. These were 38.4% vs 9.4%, 12.8% vs 4.2%, and 30.2% vs 9.4%, respectively. The difference of perinatal mortality between the patients with ICP diagnosed by using and not using the grading system (0.7% - 1.2% vs 3.9% - 6.0%) was statistically significant (P < 0.01)., Conclusion: Grading of ICP based on liver function test may improve perinatal prognosis.