甘草酸二胺与复方甘草酸苷治疗环磷酰胺所致的药物性肝损伤患者疗效研究*

doi:10.3969/j.issn.1672-5069.2023.03.022

摘要/Abstract

摘要： 目的比较应用甘草酸二胺与复方甘草酸苷治疗环磷酰胺所致的药物性肝损伤(DILI)患者的效果。方法 2018年7月～2021年1月南通市肿瘤医院就诊的因应用环磷酰胺抗肿瘤治疗诱发的DILI患者97例,随机分为对照组47例和研究组50例,分别接受复方甘草酸苷或甘草酸二铵治疗,观察6个月。采用黄嘌呤氧化酶法检测血清丙二醛(MDA)、还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和晚期蛋白氧化产物(APOPs);采用ELISA法检测血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平、一氧化氮(NO)和巨噬细胞移动抑制因子(MIF)。结果在6个月治疗结束时,研究组血清总胆红素、丙氨酸氨基转移酶和谷氨酰转肽酶水平分别为(12.3±1.5)μmol/L、(34.9±9.5)U/L和(36.9±8.8)U/L,显著低于对照组【分别为(21.7±3.1)μmol/L、(75.3±18.2)U/L和(74.2±15.2)U/L,P＜0.01】;研究组血清TNF-α、IL-6和MIF水平分别为(4.1±0.8)ng/ml、(17.6±5.3)pg/ml和(6.0±0.5)ng/mL,显著低于对照组【分别为(5.9±1.2)ng/ml、(28.8±6.1)pg/ml和(10.7±0.9)ng/mL,P＜0.01】;研究组血清丙二醛和APOPs水平分别为(4.3±0.7)μmol/L和(2.4±0.2)μmol/L,显著低于对照组【分别为(6.4±1.2)μmol/L和(4.3±0.5)μmol/L,P＜0.01】,而血清SOD和GSH水平分别为(83.6±7.9)U/L和(7.6±1.5)μmol/L,显著高于对照组【分别为(75.2±9.2)U/L和(6.4±1.2)μmol/L,P＜0.01】;在随访1年结束时,97例肿瘤患者死亡25例(25.8%)。结论相比于复方甘草酸苷治疗环磷酰胺所致DILI患者,甘草酸二铵治疗更有助于改善炎症因子,促进肝功能恢复。

关键词: 药物性肝损伤, 环磷酰胺, 甘草酸二铵, 复方甘草酸苷, 治疗

Abstract: Objective The aim of this study was to compare the efficacy of glycyrrhizic acid diamine and compound glycyrrhizin in the treatment of patients with drug-induced liver injuries (DILI). Methods 97 tumor patients with DILI caused by cyclophosphamide were encountered in Nantong Tumor Hospital between July 2018 and January 2021, and were randomly divided into control group (n=47) and observation group (n=50), receiving compound glycyrrhizin or glycyrrhizic acid diamine, respectively for six months. Serum malonaldehyde (MDA), reduced glutathione (GSH), superoxide dismutase, (SOD) and advanced protein oxidation products (APOPs) levels were detected by purine oxidase; Serum interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), nitric oxide (NO) and macrophage migration inhibitory factor (MIF) levels were determined by ELISA. Results At the end of six month observation, serum bilirubin, ALT and GGT levels in the observation group were(12.3±1.5)μmol/L, (34.9±9.5)U/L and (36.9±8.8)U/L, significantly lower than [(21.7±3.1)μmol/L, (75.3±18.2)U/L and (74.2±15.2)U/L, respectively, P＜0.01] in the control; serum TNF-α, IL-6 and MIF levels were (4.1±0.8)ng/ml, (17.6±5.3)pg/ml and (6.0±0.5)ng/mL, significantly lower than [(5.9±1.2)ng/ml,(28.8±6.1)pg/ml and (10.7±0.9)ng/mL, respectively, P＜0.01] in the control group; serum MDA and APOPs levels were (4.3±0.7)μmol/L and (2.4±0.2)μmol/L, significantly lower than [(6.4±1.2)μmol/L and (4.3±0.5)μmol/L, P＜0.01], while serum SOD and GSH levels were (83.6±7.9)U/L and (7.6±1.5)μmol/L, significantly higher than [(75.2±9.2)U/L and (6.4±1.2)μmol/L, P＜0.01] in the control; at the end of one-year follow-up, 25 patients(25.8%) died of malignant tumors in our series. Conclusion The oral administration of glycyrrhizic acid diamine in the treatment of patients with DILI caused by cyclophosphamide is convenient and seems to be more efficacious compared with compound glycyrrhizin, which could improve liver function index normal and inhibit the inflammatory reactions and oxidative stress.

Key words: Drug-induced liver injury, Cyclophosphamide, Glycyrrhizic acid diamine, Compound glycyrrhizin, Therapy

卫栋萍, 韩黎黎, 凌佳慧, 顾晓琴, 曹永峰. 甘草酸二胺与复方甘草酸苷治疗环磷酰胺所致的药物性肝损伤患者疗效研究^*[J]. 实用肝脏病杂志, 2023, 26(3): 388-391.

Wei Dongping, Han Lili, Ling Jiahui, et al.. Efficacy of glycyrrhizic acid diamine and compound glycyrrhizin in the treatment of patients with cyclophosphamide-induced liver injury[J]. Journal of Practical Hepatology, 2023, 26(3): 388-391.

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甘草酸二胺与复方甘草酸苷治疗环磷酰胺所致的药物性肝损伤患者疗效研究^*

Efficacy of glycyrrhizic acid diamine and compound glycyrrhizin in the treatment of patients with cyclophosphamide-induced liver injury

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