法尼酯衍生物X受体与不同引流方式下梗阻性黄疸大鼠部分肝切除术后肝再生的关系

Relationship between farnesoid X receptor and liver regeneration of obstructive jaundice rats following partial hepatectomy with different biliary drainages

目的 探讨法尼酯衍生物X受体（FXR）与不同引流方式下梗阻性黄疸（OJ）大鼠部分肝切除术（PH）后肝再生差异的关系.方法 120只健康雄性大鼠随机分为4组：正常大鼠70％肝切除组（Control组）、梗阻性黄疸未引流切除组（OJ组）、梗阻性黄疸内引流切除组（ID组）、梗阻性黄疸外引流切除组（ED组）.术后0、4、12、24、48、72 h等时间点检测大鼠血清总胆汁酸（TBA）含量,残肝组织FXR mRNA和蛋白表达、胆固醇7α-羟化酶（CYP7A1） mRNA表达.结果 ED组PH后12～72 h各时点增殖细胞核抗原（PCNA）阳性表达率为（19.52±1.87）％、（30.16 ±2.65）％、（46.44±2.66）％、（44.36±3.82）％,均明显低于ID组和Control组（P ＜0.05）;ED组TBA含量各时点分别为（20.38 ±4.33）、（25.87±8.68）、（35.05±6.87）、（49.66±6.65）、（60.44±7.66）、（52.36±8.82） μmol/L,均低于Control组和ID组（P＜0.05）;CYP7A1 mRNA相对表达量ED组各时段分别为1.75±0.09、1.68±0.14、1.53±0.16、1.25±0.16、1.17±0.18、1.24±0.16,均高于Control组和ID组（P＜0.05）,ID组各时点FXR mRNA相对表达量分别为1.52±0.18、1.80 ±0.12、1.89±0.12、2.56±0.09、2.39±0.20、2.02±0.24,均高于ED组（P＜0.05）,FXR蛋白表达与FXR mRNA基本一致;各项指标ID组与Control组各时点差异无统计学意义（P＞0.05）.结论 经外引流的梗阻性黄疸大鼠部分肝切除后肝再生较内引流明显抑制的原因与胆酸丢失有关,可能机制为低表达的FXR抑制了肝再生.

Objective To evaluate the relationship between farnesoid X receptor （FXR） and liver regeneration of obstructive jaundice （OJ） rats following partial hepatectomy （PH） with different biliary drainages.Methods 120 male Sprague-Dawley rats were randomly allocated into 4 groups：control group,normal rats subjected to PH （70% hepatectomy） ; OJ group,OJ rats without drainage subjected to PH; internal drainage （ID） group,OJ rats with ID subjected to PH; external drainage （ED） group,OJ rats with ED subjected to PH.The expression of FXR mRNA and protein and cholesterol 7α-hydroxylase （CYP7A1）mRNA in liver tissue,and total bile acid （TBA） content in the blood were examined at0,4,12,24,48,72 h after operation.Results The positive rate of proliferating cell nuclear antigen （PCNA） [（19.52 ±1.87）%,（30.16 ±2.65）%,（46.44 ±2.66）%,（44.36 ±3.82）%] during 12 to 72 h after PH in ED group was obviously lower than that in control and ID groups （P 〈 0.05）.The TBA content in ED group [（20.38±4.33）,（25.87 ±8.68）,（35.05 ±6.87）,（49.66±6.65）,（60.44±7.66）,（52.36±8.82） μmol/L] during 0 to 72 h after PH was obviously lower than that in control and ID groups （P〈0.05）.The relative quantitative expression of CYP7A1 mRNA in ED group （1.75 ±0.09,1.68 ±0.14,1.53 ±0.16,1.25 ±0.16,1.17 ±0.18,1.24 ±0.16） during 0 to 72 h after PH was obviously higher than that in control and ID groups （P 〈 0.05）.The relative quantitative expression of FXR mRNA in ID group [（1.52±0.18）,（1.80±0.12）,（1.89±0.12）,（2.56 ±0.09）,（2.39 ±0.20）,（2.02 ±0.24）] during 0 to 72 h after PH was obviously higher than that in ED group （P 〈 0.05）.The expression of FXR protein was corresponded with FXR mRNA generally.There was no statistically significant difference between ID and control groups in each index （P 〉 0.05）.Conclusion The inhibition of the liver regeneration in the OJ rats after PH with ED versus ID is related with the reduction in the bile acid pool size,which may be caused by the down-regulation of FXR expression.