熊去氧胆酸治疗原发性胆汁性胆管炎患者疗效及对血清Nrf2和HO-1水平的影响

Efficacy of ursodeoxycholic acid in the treatment of patients with primary biliary cholangitis and cirrhosis and its effect on serum Nrf2 and HO-1 levels

目的探讨熊去氧胆酸(UDCA)治疗原发性胆汁性胆管炎和肝硬化(PBC)患者疗效及对血清核因子相关因子2(Nrf2)和血红素加氧酶-1(HO-1)水平的影响。方法2017年1月~2020年1月我院诊治的原发性胆汁性胆管炎患者31例和原发性胆汁性肝硬化患者34例(Child A级15例,Child B级12例,Child C级7例),给予所有患者UDCA治疗。另选43例健康人作为对照。;采用硫代巴比妥酸化学比色法检测血清丙二醛(MDA),采用黄嘌呤氧化酶法测定血清超氧化物歧化酶(SOD),采用ELISA法检测血清Nrf2和HO-1水平。结果治疗前,肝硬化患者血清GGT和ALP水平分别为(389.4±29.7)U/L和(457.9±73.8)U/L,显著高于胆管炎组[分别为(173.5±16.4)U/L和(298.3±52.1)U/L,P<0.05];在治疗观察12个月末,血清GGT和ALP水平分别为(174.1±10.4)U/L和(144.6±24.5)U/L,仍显著高于胆管炎组[分别为(72.6±7.1)U/L和(95.7±11.6)U/L,P<0.05];健康人血清Nrf2、HO-1、MDA和SOD水平分别为(182.3±30.6)U/L、(12.2±2.1)U/L、(4.1±0.7)mol/L和(102.3±17.8)U/mL;治疗后,肝硬化组血清Nrf2、HO-1和MDA水平分别为(712.6±100.1)U/L、(25.1±4.3)U/L和(7.6±1.3)mol/L,显著高于胆管炎组[分别为(665.3±90.5)U/L、(21.3±3.8)U/L和(6.5±1.1)mol/L,P<0.05],而血清SOD水平为(80.6±14.5)U/mL,显著低于胆管炎组[(90.8±15.6)U/mL,P<0.05];治疗后,不同Child分级的肝硬化患者血清Nrf2、HO-1、MDA和SOD水平比较,差异均无统计学意义(P>0.05)。结论应用UDCA治疗原发性胆汁性胆管炎和肝硬化患者可改善胆汁淤积,促进肝功能恢复,可能与其抑制了氧化应激反应,提升血清Nrf2和HO-1水平有关。

Objective The aim of this study was to summarize the efficacy of ursodeoxycholic acid(UDCA)in the treatment of patients with primary biliary cholangitis(PBC)and cirrhosis and its effect on serum nuclear factor-related factor 2(Nrf2)and hemeoxygenase-1(HO-1)levels.Methods 31 patients with PBC and 34 patients with primary biliary cirrhosis(Child A in 15,Child B in 12 and Child C in 7 cases)were recruited in our hospital between January 2017 and January 2020,and 43 healthy persons were selected as control group.The patients with cholangitis and cirrhosis were all treated with UDCA for 12 months.Serum malondialdehyde(MDA),superoxide dismutase(SOD),Nrf2 and HO-1 levels were detected.Results At presentation,serum GGT and ALP levels in patients with primary biliary cirrhosis were(389.4±29.7)U/L and(457.9±73.8)U/L,both significantly higher than[(173.5±16.4)U/L and(298.3±52.1)U/L,respectively,P<0.05]in patients with primary biliary cholangitis;at the end of 12 month treatment,serum GGT and ALP levels in patients with primary biliary cirrhosis were(174.1±10.4)U/L and(144.6±24.5)U/L,still significantly higher than[(72.6±7.1)U/L and(95.7±11.6)U/L,respectively,P<0.05]in patients with primary biliary cholangitis;serum Nrf2,HO-1,MDA and SOD levels in healthy individuals were(182.3±30.6)U/L,(12.2±2.1)U/L,(4.1±0.7)mol/L and(102.3±17.8)U/mL;at 12 month observation,serum Nrf2,HO-1 and MDA levels in patients with primary biliary cirrhosis were(712.6±100.1)U/L,(25.1±4.3)U/L and(7.6±1.3)mol/L,all significantly higher than[(665.3±90.5)U/L,(21.3±3.8)U/L and(6.5±1.1)mol/L,respectively,P<0.05],while serum SOD level was(80.6±14.5)U/mL,significantly lower than[(90.8±15.6)U/mL,P<0.05]in patients with primary biliary cholangitis;there were no significant differences as respect to serum Nrf2,HO-1,MDA and SOD levels in cirrhotics with Child class A,B and C(P>0.05).Conclusion The continuous administration of UDCA could improve the liver function test normalization in patients with PCB and cirrhosis,which might be related to the amelioration of cholestasis,inhibition of oxidative stress,and increase serum Nrf2 and HO-1 levels.