Objective::This study aimed at investigating the expression of nuclear factor kappa B (NF-κB) and mammalian target of rapamycin (mTOR) related signal pathways in liver tissues of intrahepatic cholestasis of pregnancy animal models.Methods::Estrogen (EE)-induced cholestasis and a placental ischemia-reperfusion (IR) model were established in pregnant rats. All pregnant rats were divided into four groups by random number table: EE-IR group ( n= 6), EE-sham group ( n = 6), control-IR group ( n= 6) and control-sham group ( n= 6). Liver expression of mTOR, its upstream regulator DNA damage response-1 (REDD1), and downstream factor glucose transporter type-1 (GLUT1), accompanied by NF-κB (p65 is the most important component), its activator toll-like receptor 4 (TLR4), and inhibitor IκBα, were detected by western blot analysis and real-time polymerase chain reaction. The intergroup comparisons were performed with a one-way analysis of variance, the comparisons among groups were analyzed with the nonparametric Kruskal-Wallis test. Results::Giving pregnant rats EE alone reduced the hepatic expression of IκBα (0.72 ± 0.20 vs. 1.01 ± 0.07, P= 0.008). Meanwhile, giving pregnant rats placental IR alone increased liver levels of REDD1 (3.24 ± 0.98 vs. 1.06 ± 0.24, P= 0.025), GLUT1 (2.37 ± 0.82 vs. 1.09 ± 0.10, P= 0.039), TLR4 (2.12 ± 0.29 vs. 1.20 ± 0.28, P= 0.010), and p65 (2.09 ± 0.85 vs. 1.04 ± 0.06, P= 0.023), and decreased hepatic mTOR (0.50 ± 0.07 vs. 1.01 ± 0.03, P= 0.001) and IκBα (0.61 ± 0.08 vs. 1.01 ± 0.07, P= 0.014) expression. Subjecting EE-treated rats to placental IR did not further alter liver levels of GLUT1 (2.02 ± 0.45 vs. 1.79 ± 0.39, P= 0.240), TLR4 (2.10 ± 0.74 vs. 1.60 ± 0.36, P= 0.129), or p65 (2.41 ± 0.83 vs. 1.65 ± 0.46, P= 0.145), whereas it did decrease hepatic mTOR (0.42 ± 0.09 vs. 0.90 ± 0.14, P= 0.008) and IκBα (0.43 ± 0.09 vs. 0.72 ± 0.20, P= 0.004) expression and enhance REDD1 expression (4.46 ± 0.65 vs. 2.05 ± 0.47, P= 0.009). Placental IR stress did impact the hepatic expression of REDD1-mTOR-GLUT1 and TLR4/NF-κB/IκBα in pregnant rats. Conclusion::Placental IR-induced hepatic GLUT1, TLR4, and p65 alternation, which responded efficiently in control rats, were impaired in EE-induced ICP rats.

Cholestasis, intrahepatic;Liver;mTOR;Pregnancy

Zhou Fan;Chen Huafang;Shan Dan;Wu Yuxia;Chen Qian;Hu Yayi

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China;Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan 610041, China

母胎医学杂志（英文）

[1]Zhou Fan;Chen Huafang;Shan Dan;Wu Yuxia;Chen Qian;Hu Yayi-.Dysregulated Hepatic Expression of Glucose Transporter Type-1, Toll-Like Receptor 4, and Nuclear Factor Kappa B in Estrogen-Induced Cholestasis Pregnant Rats with Placental Ischemia-Reperfusion Stress)[J].母胎医学杂志（英文）,2022(01):17-23

Cholestasis,REDD1,08 ,Subjecting

Dysregulated,Hepatic,Expression,Glucose,Transporter,Type,Toll,Like,Receptor,Nuclear,Factor,Kappa,Estrogen,Induced,Pregnant,Rats,Placental,Ischemia,Reperfusion,Stress,Objective,This,study,aimed,investigating,expression,nuclear,kappa,mammalian,target,rapamycin,mTOR,related,signal,pathways,liver,tissues,intrahepatic,cholestasis,pregnancy,animal,models,Methods,EE,induced,placental,ischemia,reperfusion,were,established,pregnant,rats,All,divided,into,four,groups,by,random,number,table,sham,control,Liver,its,upstream,regulator,damage,response,downstream,glucose,transporter,type,GLUT1,accompanied,p65,most,important,component,activator,toll,like,receptor,TLR4,inhibitor,detected,western,blot,analysis,real,polymerase,chain,reaction,intergroup,comparisons,performed,variance,among,analyzed,nonparametric,Kruskal,Wallis,test,Results,Giving,alone,reduced,20 ,Meanwhile,giving,increased,levels,decreased,treated,did,not,further,whereas,09 ,enhance,stress,impact,Conclusion,alternation,which,responded,efficiently,impaired,ICP,Pregnancy

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