布地奈德治疗熊去氧胆酸治疗不应答的原发性胆汁性胆管炎患者疗效及血清氧化应激指标的变化*

doi:10.3969/j.issn.1672-5069.2023.03.019

摘要/Abstract

摘要： 目的探讨布地奈德治疗对熊去氧胆酸(UDCA)治疗不应答的原发性胆汁性胆管炎(PBC)患者的疗效。方法 2019年2月～2022年2月我院收治的非肝硬化PBC患者76例,采用随机数字表法将其分为对照组(n=38)和观察组(n=38),分别继续给予UDCA或UDCA联合布地奈德治疗24 w。采用ELISA法检测血清白细胞介素-2(IL-2)、IL-6、IL-10、丙二醛(MDA)、超氧化物歧化酶(SOD)、血红素加氧酶-1(HO-1)和核因子相关因子2(Nrf2),采用免疫比浊法检测血浆免疫球蛋白M(IgM)、IgG和IgA。结果在治疗24 w末,观察组血清ALP、GGT和TBIL水平分别为(97.6±18.5) U/L、(82.4±10.2) U/L和(25.4±4.2)μmol/L,均显著低于对照组【分别为(234.8±40.6) U/L、(160.6±17.6) U/L和(34.5±6.1)μmol/L,P＜0.05】;血清IL-2和IL-10水平分别为(62.9±15.7)pg/ml和154.9±12.8)pg/ml,显著高于对照组【分别为(37.4±18.3)pg/ml和(89.6±17.6) pg/ml,P＜0.05】,而血清IL-6水平为(5.3±1.3) pg/ml,显著低于对照组【(7.9±1.7) pg/ml,P＜0.05】;血浆IgM、IgG和IgA水平分别为(2.4±0.3) g/L、(11.2±1.9) g/L和(2.8±0.4) g/L,均显著低于对照组【(4.1±0.5) g/L、(15.7±2.4)g/L和(4.4±0.6) g/L,P＜0.05】;血清MDA水平为(5.2±0.7)μmol/L,显著低于对照组【(7.9±1.1)μmol/L,P＜0.05】,而血清SOD、HO-1和Nrf2水平分别为(86.2±9.6) U/L、(22.1±2.9) U/L和(669.8±87.6) U/L,均显著高于对照组【分别为(72.5±8.2) U/L、(16.8±2.5) U/L和(547.5±80.4) U/L,P＜0.05】。结论应用布地奈德治疗UDCA治疗不应答的PBC患者能促进肝功能恢复,可能与调节了细胞因子和免疫球蛋白水平及抑制氧化应激反应有关。

关键词: 原发性胆汁性胆管炎, 布地奈德, 熊去氧胆酸, 氧化应激, 治疗

Abstract: Objective The aim of this study was to explore the rescued therapy of budesonide in patients with primary biliary cholangitis (PBC) for poor response to ursodeoxycholic acid (UDCA) treatment. Methods 76 patients with PBC who had not response to UDCA treatment were recruited in our hospital between February 2019 and February 2022, and were divided randomly into control group (n=38) and observation group (n=38). The patients in the control group maintained treatment with UDCA, and those in the observation group were treated with budesonide at base of UDCA treatment. The observation lasted for 24 weeks. Serum interleukin-2 (IL-2), IL-6, IL-10, malondialdehyde (MDA), superoxide dismutase (SOD), hemeoxygenase-1(HO-1) and nuclear factor-related factor 2(Nrf2) levels were detected by ELISA. Plasma immunoglobulin levels were detected by turbidimetric inhibition immnoassay. Results At the end of 24 week treatment, serum ALP, GGT and bilirubin levels in the observation group were (97.6±18.5) U/L, (82.4±10.2) U/L and (25.4±4.2)μmol/L, all significantly lower than [(234.8±40.6) U/L, (160.6±17.6) U/L and (34.5±6.1)μmol/L, respectively, P＜0.05] in the control; serum IL-2 and IL-10 levels were (62.9±15.7) pg/ml and 154.9±12.8)pg/ml, both significantly higher than [(37.4±18.3) pg/ml and (89.6±17.6) pg/ml, respectively, P＜0.05], while serum IL-6 levels was (5.3±1.3) pg/ml, much lower than [(7.9±1.7) pg/ml, P＜0.05] in the control; plasma IgM, IgG and IgA levels were (2.4±0.3) g/L, (11.2±1.9) g/L and (2.8±0.4) g/L, all significantly lower than [(4.1±0.5) g/L, (15.7±2.4)g/L and (4.4±0.6) g/L, respectively, P＜0.05]; serum MDA level was (5.2±0.7)μmol/L, much lower than [(7.9±1.1)μmol/L, P＜0.05], while serum SOD, HO-1 and Nrf2 levels were (86.2±9.6)U/L, (22.1±2.9) U/L and (669.8±87.6) U/L, all significantly higher than [(72.5±8.2) U/L, (16.8±2.5) U/L and (547.5±80.4) U/L, respectively, P＜0.05] in the control group. Conclusion The rescue treatment of budesonide in PBC patients without response to UDCA therapy could improve the recovery of liver function tests, which might be related to the regulation of immune system and inhibition of oxidative stress.

Key words: Primary biliary cholangitis, Budesonide, Ursodeoxycholic acid, Oxidative stress, Treatment

何学元, 马建勋, 杨屹立, 张敏, 潘新民. 布地奈德治疗熊去氧胆酸治疗不应答的原发性胆汁性胆管炎患者疗效及血清氧化应激指标的变化^*[J]. 实用肝脏病杂志, 2023, 26(3): 376-379.

He Xueyuan, Ma Jianxun, Yang Yili, et al.. Rescued therapy of budesonide in patients with primary biliary cholangitis for poor response to ursodeoxycholic acid treatment[J]. Journal of Practical Hepatology, 2023, 26(3): 376-379.

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布地奈德治疗熊去氧胆酸治疗不应答的原发性胆汁性胆管炎患者疗效及血清氧化应激指标的变化^*

Rescued therapy of budesonide in patients with primary biliary cholangitis for poor response to ursodeoxycholic acid treatment

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