Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian 116001, Liaoning Province, China.
World J Gastroenterol. 2011 Jan 21;17(3):322-8. doi: 10.3748/wjg.v17.i3.322.
To investigate the role of heme oxygenase-1 (HO-1) in pathogenesis of experimental hepatorenal syndrome (HRS).
Rats were divided into liver cirrhotic group, zinc protoporphyrin IX (ZnPP) treatment group, cobalt protoporphyrin (CoPP) treatment group and sham group. Biliary cirrhosis was established by bile duct ligation in the first three groups. Rats in the ZnPP and CoPP treatment groups received intraperitoneal injection of ZnPP and CoPP, respectively, 24 h before sample collection. Expression of HO-1 mRNA in kidney was detected by reverse-transcription polymerase chain reaction, while protein expression was determined by immunohistochemical analysis. Hematoxylin and eosin staining was performed to observe liver cirrhosis and renal structure. Renal artery blood flow, mean arterial pressure and portal vein pressure, 24 h total urinary volume, serum and urine sodium concentrations, and creatinine clearance rate (Ccr) were also measured.
The HO-1 mRNA and protein expression levels in kidney, 24 h total urinary volume, renal artery blood flow, serum and urine sodium concentration and Ccr were lower in cirrhotic group than in sham group (P < 0.05). However, they were significantly lower in ZnPP treatment group than in cirrhotic group and significantly higher in CoPP treatment group than in cirrhotic group (P < 0.05).
Low HO-1 expression level in kidney is an important factor for experimental HRS.
探讨血红素加氧酶-1(HO-1)在实验性肝肾综合征(HRS)发病机制中的作用。
将大鼠分为肝硬化组、锌原卟啉 IX(ZnPP)治疗组、钴原卟啉(CoPP)治疗组和假手术组。前三组均采用胆管结扎法建立胆汁性肝硬化。ZnPP 和 CoPP 治疗组大鼠在采集样本前 24 小时分别接受腹腔注射 ZnPP 和 CoPP。采用逆转录聚合酶链反应检测肾脏 HO-1 mRNA 的表达,免疫组织化学分析检测蛋白表达。苏木精-伊红染色观察肝脏和肾脏的结构。还测量了肾动脉血流、平均动脉压和门静脉压、24 小时总尿量、血清和尿钠浓度以及肌酐清除率(Ccr)。
与假手术组相比,肝硬化组肾脏 HO-1 mRNA 和蛋白表达水平、24 小时总尿量、肾动脉血流、血清和尿钠浓度及 Ccr 均降低(P<0.05)。然而,ZnPP 治疗组的这些指标均明显低于肝硬化组,CoPP 治疗组的这些指标均明显高于肝硬化组(P<0.05)。
肾脏中 HO-1 表达水平降低是实验性 HRS 的一个重要因素。