四逆汤加味联合异甘草酸镁治疗急性药物性肝损伤疗效及对氧化应激、体液免疫功能的影响
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摘要
目的探讨四逆汤加味联合异甘草酸镁治疗急性药物性肝损伤(ADILI)疗效及对氧化应激、体液免疫功能的影响。方法将110例ADILI患者按照随机数字表法分为观察组和对照组,每组55例。对照组患者给予常规保肝及异甘草酸镁静滴治疗,观察组在对照组基础上给予四逆汤加味口服治疗,2组疗程均为4周。观察2组治疗后临床症状体征、ADILI分级情况、肝功能、氧化应激和体液免疫指标变化情况,统计2组临床疗效及不良反应发生情况。结果治疗后2组肝区隐痛、恶心呕吐、食欲减退、腹胀、乏力、皮肤泛黄、尿黄、皮疹发生率均显著降低(P均<0. 05),且观察组显著低于对照组(P均<0. 05)。治疗后2组ADILI分级均显著改善(P均<0. 05),观察组改善情况显著优于对照组(P均<0. 05)。治疗后2组丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、总胆红素(TBil)、谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、丙二醛(MDA)、Ig G、Ig A、Ig M水平均显著降低(P均<0. 05),还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)水平均显著升高(P均<0. 05),观察组治疗后以上指标改善情况均显著优于对照组(P均<0. 05)。观察组治疗总有效率显著高于对照组(P <0. 05)。2组不良反应发生情况无明显差异(P> 0. 05)。结论四逆汤加味联合异甘草酸镁治疗ADILI可显著缓解患者临床症状,具有显著的肝保护效应,且不良反应少,其机制可能与抑制氧化应激反应、调节机体体液免疫功能有关。
Objective It is to investigate the curative effect of Sini Decoction combined with magnesium isoglycyrrhizinate on acute drug-induced liver injury( ADILI) and its effects on oxidative stress and humoral immunity. Methods 110 patients with ADILI were divided into observation group and control group according to the random number table method,55 cases in each group. The patients in the control group were treated with routine liver protection and intravenous treatment with magnesium isoglycyrrhizinate. The observation group was given oral administration of Sini Decoction on the basis of the control group. Both groups were treated for 4 weeks. The clinical symptoms and signs,ADILI grading,liver function,oxidative stress and humoral immunity indexes of the two groups were observed after treatment. The clinical efficacy and adverse reactions of the two groups were statistically analyzed. Results After treatment,the incidence of dull pain in liver,nausea and vomiting,loss of appetite,abdominal distension,fatigue,skin yellowing,urine yellow and rash were significantly decreased in the two groups( P < 0. 05),and the incidence in the observation group was significantly lower than that in the control group( P < 0. 05). After treatment,the ADILI grades of the two groups were significantly improved( P <0. 05),and the improvement of the observation group was significantly better than that of the control group( P < 0. 05).After treatment,the levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),total bilirubin( TBil),glutamyl transpeptidase( GGT),alkaline phosphatase( ALP),malondialdehyde( MDA),Ig G,Ig A and Ig M were significantly decreased( P < 0. 05),and the levels of reduced glutathione( GSH) and superoxide dismutase( SOD) were significantly increased( P < 0. 05),the improvement of the above indicators in the observation group was significantly better than that in the control group( P < 0. 05). The total effective rate of the observation group was significantly higher than that of the control group( P < 0. 05). There was no significant difference in the incidence of adverse reactions between the two groups( P > 0. 05). Conclusion Sini decoction combined with magnesium isoglycyrrhizinate can significantly alleviate the clinical symptoms of patients with ADILI. It has significant hepatoprotective effects and few adverse reactions. The mechanism may be related to inhibition of oxidative stress and regulation of humoral immunity.
Objective It is to investigate the curative effect of Sini Decoction combined with magnesium isoglycyrrhizinate on acute drug-induced liver injury( ADILI) and its effects on oxidative stress and humoral immunity. Methods 110 patients with ADILI were divided into observation group and control group according to the random number table method,55 cases in each group. The patients in the control group were treated with routine liver protection and intravenous treatment with magnesium isoglycyrrhizinate. The observation group was given oral administration of Sini Decoction on the basis of the control group. Both groups were treated for 4 weeks. The clinical symptoms and signs,ADILI grading,liver function,oxidative stress and humoral immunity indexes of the two groups were observed after treatment. The clinical efficacy and adverse reactions of the two groups were statistically analyzed. Results After treatment,the incidence of dull pain in liver,nausea and vomiting,loss of appetite,abdominal distension,fatigue,skin yellowing,urine yellow and rash were significantly decreased in the two groups( P < 0. 05),and the incidence in the observation group was significantly lower than that in the control group( P < 0. 05). After treatment,the ADILI grades of the two groups were significantly improved( P <0. 05),and the improvement of the observation group was significantly better than that of the control group( P < 0. 05).After treatment,the levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),total bilirubin( TBil),glutamyl transpeptidase( GGT),alkaline phosphatase( ALP),malondialdehyde( MDA),Ig G,Ig A and Ig M were significantly decreased( P < 0. 05),and the levels of reduced glutathione( GSH) and superoxide dismutase( SOD) were significantly increased( P < 0. 05),the improvement of the above indicators in the observation group was significantly better than that in the control group( P < 0. 05). The total effective rate of the observation group was significantly higher than that of the control group( P < 0. 05). There was no significant difference in the incidence of adverse reactions between the two groups( P > 0. 05). Conclusion Sini decoction combined with magnesium isoglycyrrhizinate can significantly alleviate the clinical symptoms of patients with ADILI. It has significant hepatoprotective effects and few adverse reactions. The mechanism may be related to inhibition of oxidative stress and regulation of humoral immunity.
引文
[1]齐芬,任晓非,许建明.急性药物性肝损伤的临床研究[J].安徽医药,2016,20(8):1603-1605
[2]贺蕾艳,郭瑶雪,李春,等.药物性肝损伤生物标志物研究进展[J].药学学报,2015,50(8):959-965
[3]杨柯柯,廖锦堂. ARFI评价急性药物性肝损伤的临床研究[J].肝脏,2016,21(5):338-340
[4]朱云,成佳黛,王立福,等.中医药治疗药物性肝损伤的研究概况[J].中西医结合肝病杂志,2014,24(4):254-256
[5]熊周勇.中医药治疗肝病的临床体会[J].实用中西医结合临床,2007,7(1):82-83
[6]于乐成,茅益民,陈成伟.药物性肝损伤诊治指南[J].中华肝脏病杂志,2015,23(11):1752-1769
[7] Chalasani NP,Hayashi PH,Bonkovsky HL,et al. ACG Clinical Guideline:The Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury[J]. Am J Gastroenterol,2014,109(7):950-966
[8]国家中医药管理局.中医病证诊断疗效标准[S].南京:南京大学出版社,1994:118-119
[9]鲍中英.药物性肝损伤的发病机制[J/CD].中华临床医师杂志:电子版,2015,9(19):1-3
[10]张红阳,李雪溦,姚雪莲,等.肝损伤的分子机制及其中药药理研究进展[J].中药新药与临床药理,2016,27(3):448-455
[11]孙信林,吴玮,周建,等.氢饱和水对初治肺结核患者血清XOD、MDA、SOD、GST水平及药物性肝损伤的影响[J].实用临床医药杂志,2016,20(21):34-37
[12]马磊,陈欢,许婉婷,等.探讨血红素加氧酶-1在利福平致肝氧化应激损伤中的作用[J].重庆医科大学学报,2016,41(6):587-592
[13]陈成伟.重视药物性肝损伤免疫机制的研究[J].肝脏,2016,21(5):397-398
[14]周璐,王邦茂.药物性肝损伤的免疫学研究进展[J].胃肠病学,2014,19(11):641-643
[15]李小鹏,李明,雷弯,等.异甘草酸镁对D-氨基半乳糖致急性肝衰竭大鼠模型的保护作用[J].临床肝胆病杂志,2016,32(3):545-548
[16]陈鑫,葛芹,张彩云,等.异甘草酸镁对CCl4致急性肝损伤大鼠肝组织CYP1A2、CYP2E1蛋白及其mRNA表达的影响[J].安徽中医药大学学报,2017,36(1):55-58
[17]耿睿韬,赵文霞.中医药治疗药物性肝损伤的研究进展[J].中国继续医学教育,2015,7(20):195-196
[18]汪瑶.附子理中汤在消化系统疾病中的应用[J].世界华人消化杂志,2017,25(8):716-721
[19]杨润华,陈娇,高戎,等.茵陈蒿汤治疗脓毒症相关肝损伤的临床应用研究[J].中国中西医结合急救杂志,2016,23(3):248-252
[20]韩向北,朱彤彤,郭亚雄,等.郁金对CCl4所致急性肝损伤小鼠肝脏的免疫调节作用[J].吉林大学学报:医学版,2010,36(5):934-937
[21]郭秋芳,赵康路,郭意男,等.土茯苓组方对急性肝衰竭大鼠保护作用的实验研究[J].浙江临床医学,2017,19(5):811-813
[22]何苗.甘草黄酮分散片对小鼠肝损伤的保护作用[D].兰州:兰州大学,2017:11-13
[2]贺蕾艳,郭瑶雪,李春,等.药物性肝损伤生物标志物研究进展[J].药学学报,2015,50(8):959-965
[3]杨柯柯,廖锦堂. ARFI评价急性药物性肝损伤的临床研究[J].肝脏,2016,21(5):338-340
[4]朱云,成佳黛,王立福,等.中医药治疗药物性肝损伤的研究概况[J].中西医结合肝病杂志,2014,24(4):254-256
[5]熊周勇.中医药治疗肝病的临床体会[J].实用中西医结合临床,2007,7(1):82-83
[6]于乐成,茅益民,陈成伟.药物性肝损伤诊治指南[J].中华肝脏病杂志,2015,23(11):1752-1769
[7] Chalasani NP,Hayashi PH,Bonkovsky HL,et al. ACG Clinical Guideline:The Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury[J]. Am J Gastroenterol,2014,109(7):950-966
[8]国家中医药管理局.中医病证诊断疗效标准[S].南京:南京大学出版社,1994:118-119
[9]鲍中英.药物性肝损伤的发病机制[J/CD].中华临床医师杂志:电子版,2015,9(19):1-3
[10]张红阳,李雪溦,姚雪莲,等.肝损伤的分子机制及其中药药理研究进展[J].中药新药与临床药理,2016,27(3):448-455
[11]孙信林,吴玮,周建,等.氢饱和水对初治肺结核患者血清XOD、MDA、SOD、GST水平及药物性肝损伤的影响[J].实用临床医药杂志,2016,20(21):34-37
[12]马磊,陈欢,许婉婷,等.探讨血红素加氧酶-1在利福平致肝氧化应激损伤中的作用[J].重庆医科大学学报,2016,41(6):587-592
[13]陈成伟.重视药物性肝损伤免疫机制的研究[J].肝脏,2016,21(5):397-398
[14]周璐,王邦茂.药物性肝损伤的免疫学研究进展[J].胃肠病学,2014,19(11):641-643
[15]李小鹏,李明,雷弯,等.异甘草酸镁对D-氨基半乳糖致急性肝衰竭大鼠模型的保护作用[J].临床肝胆病杂志,2016,32(3):545-548
[16]陈鑫,葛芹,张彩云,等.异甘草酸镁对CCl4致急性肝损伤大鼠肝组织CYP1A2、CYP2E1蛋白及其mRNA表达的影响[J].安徽中医药大学学报,2017,36(1):55-58
[17]耿睿韬,赵文霞.中医药治疗药物性肝损伤的研究进展[J].中国继续医学教育,2015,7(20):195-196
[18]汪瑶.附子理中汤在消化系统疾病中的应用[J].世界华人消化杂志,2017,25(8):716-721
[19]杨润华,陈娇,高戎,等.茵陈蒿汤治疗脓毒症相关肝损伤的临床应用研究[J].中国中西医结合急救杂志,2016,23(3):248-252
[20]韩向北,朱彤彤,郭亚雄,等.郁金对CCl4所致急性肝损伤小鼠肝脏的免疫调节作用[J].吉林大学学报:医学版,2010,36(5):934-937
[21]郭秋芳,赵康路,郭意男,等.土茯苓组方对急性肝衰竭大鼠保护作用的实验研究[J].浙江临床医学,2017,19(5):811-813
[22]何苗.甘草黄酮分散片对小鼠肝损伤的保护作用[D].兰州:兰州大学,2017:11-13