硫化氢对急性肝衰竭转运蛋白Bsep和Mdr2的调节  

Regulation of hydrogen sulfide on transporter protein Bsep and Mdr2 in acute liver failure

作　　者：王新国[1] 王炳元[2] 黄谦 张波[1] 华忠[1] 

机构地区：[1]无锡市第五人民医院脂肪肝科,江苏省214005 [2]中国医科大学附属第一医院消化科 [3]杭州市西溪医院内科

出　　处：《中华医学杂志》2015年第39期3176-3179,共4页National Medical Journal of China

基　　金：中国肝炎基金会天晴肝病基金（20120070）;杭州科委医疗卫生及重点专科专病科研攻关专项（20120633806）

摘　　要：目的 观察硫化氢对肝衰竭胆管侧膜转运蛋白Bsep、Mdr2的影响.方法 雄性SD大鼠24只,随机分为硫代乙酰胺（TAA）组、正常对照组、TAA＋硫氢化钠组和TAA＋炔丙基甘氨酸组,每组6只.用6％的TAA对TAA组及TAA＋硫氢化钠组和TAA＋炔丙基甘氨酸组动物腹腔注射造成肝衰竭;用硫氢化钠0.15 mmol/kg和炔丙基甘氨酸30 mg/kg于TAA注射之前1h腹腔注射,48 h处死动物,测定血清中的硫化氢、肝功能以及肝病理变化.利用免疫印迹和SP免疫组化方法检测肝组织胆管侧膜蛋白Bsep、Mdr2表达情况.结果 TAA导致肝脏衰竭,血清转氨酶明显升高＞10倍[ALT （524.0±32.0） U/L比（28.3±8.4）U/L],硫氢化钠使血清转氨酶升高加剧[ALT（861.9±55.1） U/L],而炔丙基甘氨酸使转氨酶下降[ALT（59.5 ±10.2）U/L].TAA引起胆红素和胆汁酸明显升高,硫氢酸钠可使胆汁酸水平进一步升高和胆红素水平下降;反之PPG导致胆汁酸胆红素均明显下降.TAA组血清硫化氢明显增加,硫氢化钠使之升高更为显著;炔丙基甘氨酸则使硫化氢含量明显下降.TAA引起肝细胞高度水肿,大片坏死,炎症细胞浸润;硫氢酸钠则使肝细胞坏死面积增大,细胞变形严重,炎症细胞浸润加重;而炔丙基甘氨酸则使肝细胞坏死减轻.肝衰竭时Bsep、Mdr2明显减少,硫氢酸钠使之进一步减少,而炔丙基甘氨酸则使减少程度缓解.结论 硫化氢促进肝衰竭时胆管侧膜蛋白转运体Bsep、Mdr2丢失并引起高胆汁酸血症.Objective To observe the effect of hydrogen sulfide on Bsep and Mdr2 in acute liver failure induced by thioacetamide.Methods Twenty-four male SD rats were randomly divided into thioacetamide （TAA） induced model group （n =6）, control group （n =6）, TAA ＋ sodium hydrosulfide group （n =6）, and TAA ＋ propargylglycine group （n =6）.TAA was given to enterocoelia at the dose of 600 mg/kg for the model group, sodium hydrosulfide group and propargylglycine group rats.Sodium hydrosulfide with the dose of 0.15 mmol/kg and propargylglycine of 30 mg/kg was injected into enterocoelia one hour before the TAA used.All rats were sacrificed and serum specimen was collected to test hydrogen sulfide and hepatic function.The method of Western blot and Immunohistochemistry were used to measure the expression of Bsep and Mdr2 in the liver.Results The Liver function of TAA group rats was severely injured [ALT（524.0 ± 32.0） vs （28.3 ± 8.4） U/L].It was worsen by application of sodium hydrosulfide [ALT（861.9 ±55.1） U/L] while recovered [ALT（59.5 ± 10.2） U/L）] by propargylglycine.The level of bilimbin and bile acid was significantly higher in the TAA group rats than in the normal control group, and the application of sodium hydrosulfide caused bile acids increased further besides of bilirubin.On the contrary, the levels of bile acids and bilirubin were significantly decreased with PPG application.The level of hydrogen sulfide in the serum of the TAA group rats was higher than normal group rats＇.That was elevated by sodium hydrosulfide and decreased by propargylglycine.Severely edema, necrosis and inflammatory cell infiltration were observed in TAA group rats, which worse by sodium hydrosulfide and released by propargylglycine.The expression of Bsep and Mdr2 down regulated in TAA and deteriorated by sodium hydrosulfide application and relieved by propargylglycine application.Conclusion Hydrogen sulfide exacerbated the Bsep and Mdr2 loss in the liver failure and contributed to high serum concentra

关 键 词：肝功能衰竭 硫化氢 载体蛋白质类 

分 类 号：R575.3[医药卫生—消化系统]