雌激素以及胆酸负荷和胆汁流失对大鼠肝胆功能的影响

Effect of estrogen,cholic acid loading and bile draining on hepatobiliaryf unctions in rats

目的妊娠期肝内胆汁瘀积症(ICP)是孕妇发生的高危肝病.为研究其发生机制和提供预防和治疗的理论依据而进行了本试验.方法选用健康、体重相似的雌性大鼠37只(清洁级),随机分成雌激素处理组(E,10只)、胆酸处理组(CA,17只)和对照组(C,10只).E 组大鼠每天注射苯甲酸雌二醇(5 mg·kg^(-1),针剂,丙三醇配制),连续5 d;C 组同时注射等量丙三醇;CA 组大鼠实验前静脉灌注胆酸(2.4 mg·kg^(-1),2 g·L^(-1)生理盐水)3次,间隔20min.所有大鼠正式实验前自眶下静脉丛采血1次,接着手术安装胆管导管收集胆汁,第1 h 每15min 收集1次,第2 h收集其总量,经2 h 于实验结束前再采血1次.血样经肝素抗凝分离血浆,胆汁则分别计量后采样.血浆和胆汁中 E_2和 GCA用放射免疫法测定,其他的肝胆功能指标用日产自动生化分析仪测定.结果雌激素使血浆 GCA,GGT,ALP 显著升高,胆固醇(CHOL)显著降低,AST 和 ALT 也有所降低;胆汁中 TBA 显著降低,总胆红素(TBIL)和 CHOL 升高,胆汁流量和流速明显减小,还可见 ALP,GGT,AST 和 ALT 有不同程度升高.胆酸灌注可显著升高血浆 E_2水平,并使 GCA 和 TBA 升高,CHOL 降低.胆汁中 GCA 和 TBA 升高,TBIL 降低,其他指标无明显变化.胆汁流失2 h,除使血浆 ALP 和胆汁 GGT 显著降低外,其他指标未见有明显差异.结论雌激素对 ICP 的发生有重要作用;注射雌激素和胆酸可引起肝胆功能明显变化;但短期胆汁流失除 ALP 和 GGT 外对其他肝胆功能指标似无显著影响.

AIM To study the effects of estrogen,cholic acid loading and bile draining on hepatobiliary functions in order to clarify the cause and pathogenesis of intrahepatic cholestasis of pregnancy (ICP) in women. METHODS Thirty-seven Wistar female rats with body mass of 170 g-200 g were randomly divided into three groups.Estrogen group (E,10),cholate group (CA,17) and control group (C,10).Rats in group E were injected with benzogynestryl (5 mg·kg^(-1)) once a day in 5 days and in group C were done the same as group E in addition to injection of benzogynestryl substituted by propylene glycol as well as the rats in group CA were infused with cholate saline solution (2.4 mg·kg^(-1),0.2% w/v) 3 times interval 20min before the experiment.Blood samples were taken from infraorbitalis V.Plexus at the beginning of experiment and then catheter was put into bile duct for collecting the bile every 15min in the first hour and total amount in second hour.After 2 h,the blood samples were also taken before experiment.Estrodiol (E_2),GCA and AST,ALT,GGT,ALP,CHOL,TBA and TBIL in plasma and bile were measured with RIAs and autobioanalyzer by enzymetic method,respectively. RESULTS Injection of benzogynestryl significantly increased the levels of E_2,GCA,GGT and ALP in plasma, and decreased plasma CHOL but no significant effect on TBA and TBIL;in contrast,the bile level of TBA significantly decreased and TBIL,CHOL,GGG and ALP in bile significantly increased;the amount and rate of bile flow significantly reduced.Injection of CA also significantly increased plasma E_2 level and GCA,TBA, AST,ALT,GGT and ALP in plasma and bile,and decreased CHOL level in plasma but in bile,and TBIL in bile significantly reduced.During bile draining,most of biochemical indexes in plasma and bile had no significant changes except that ALP in plasma and GGT in bile significantly decreased. CONCLUSION Estrogen participates in ICP and plays a significant and key role in ICP pathogenesis.Injection of estrogen and cholic acid loading obviously changes the hepatobiliary function.Bile draining in short time has no significant effect on hepatobiliary function.