Na^+-牛磺酸转运体基因在急性肝内胆汁淤积大鼠肝组织的表达及意义

Expression of Na^+-taurocholate co-transporting peptide in liver of rats with acute intrahepatic cholestatic hepatic injury

目的通过研究α-异硫氰酸萘酯(ANIT)所致的急性肝内胆汁淤积大鼠肝组织Na+-牛磺酸转运体基因(ntcp)表达的变化,以进一步探讨急性肝内胆汁淤积发生的分子机制。方法选用40只幼年雄性SD大鼠为实验对象,随机分为正常对照组(8只)、中毒组(32只)。中毒组幼鼠按100mg/kg一次性灌服ANIT诱导急性肝内胆汁淤积病变。观察各组在灌服ANIT后24、48、72和96h血清总胆红素(TB)、丙氨酸转氨酶(ALT)的浓度,同时用RT-PCR测定肝组织中ntcp-mRNA的表达,并在光学显微镜下观察肝脏的形态学改变。实验结果采用SPSS软件包分析。结果灌服ANIT后,中毒组大鼠血清ALT、TB逐渐升高,24h增加明显,48h达高峰,72h逐渐下降,96h已显著下降,差异有统计学意义(P﹤0.05)。中毒组大鼠肝组织ntcp-mRNA表达水平低于正常对照组,48h表达最低,72h逐渐恢复,差异有统计学意义(P﹤0.05)。结论ANIT所致的急性肝内胆汁淤积使肝脏功能受损,导致血清酶学改变。急性胆汁淤积肝组织基底膜ntcp基因转录水平明显下降为机体的一种负反馈机制,可减轻胆汁淤积程度,保护肝细胞。

Objective To investigate the gene expression of Na＋-taurocholate co-transporting peptide （ntcp） in liver of rats with acute intrahepatic cholestatic hepatic injury induced by alpha-naphthylisothiocyanate （ ANIT） . Methods Forty young male SD rats were randomly assigned into control group （8） and intoxication group （32）. A single dose （100 mg/kg） of ANIT was administered by gavage to each rat in intoxication group to induce intrahepatic cholestasis. The specimens of hepatic tissue and serum were collected at 24h, 48 h, 72h and 96 h after gavage. The levels of serum total bilirubin （TB） and alanine aminotransferase （ALT） were determined. The expression of ntcp- mRNA was measured by RT-PCR. Results After administration of ANIT, the levels of serum ALT and TB in the intoxication group increased gradually and peaked by 48 h. And the alteration of the intoxication group were significantly higher than those of the control group （P 0.05）. ntcp mRNA expression was significantly lower in rat liver tissue of acute intrahepatic cholestatic hepatic injury and negatively correlated with TB and ALT. Conclusions Acute intrahepatic cholestafic hepatic injury induced by ANIT lowers ntcp expression in liver tissue. ntcp gene expression has been shown to be suppressed by high levels of bile acids as an adaptive mechanism to reduce bile acids entry into the hepatocytes.