Clinical，Serum Inflammatory Cytokine，Immune，and Oxidative Stress Responses to Rougan Huaxian Granules with Transplantation of Bone Mesenchymal Stem Cells in Decompensated Cirrhosis Patients

doi:10.12114/j.issn.1007-9572.2020.00.570

Abstract

Abstract: Background　The transplantation of bone mesenchymal stem cells（BMSCs）brings hope to patients with liver cirrhosis.However，as the containing of BMSCs is very little in bone marrow and their ability of homing to the liver is limited，the clinical application of this technique is limited.The traditional Chinese medicine（TCM）mobilization program of recruiting endogenous stem cells can promote BMSCs homing to the liver，demonstrating the key role of TCM in maintaining or promoting normal regenerative repair of the body.Objective　To investigate the clinical，serum inflammatory cytokine，immune，and oxidative stress responses to Rougan Huaxian Granules with transplantation of BMSCs in decompensated cirrhosis patients.Methods　From May 2016 to May 2019，120 decompensated cirrhosis patients were selected from Liver Disease Division，the First Affiliated Hospital of Guangxi University of Chinese Medicine，and Department of Spleen，Stomach and Liver Diseases，Guangxi International Zhuang Medical Hospital，and were randomly divided into groups A，B and C，with 40 cases in each group，receiving comprehensive medical treatment，comprehensive medical treatment with BMSCs transplantation and 1-year post-transplantation antiviral therapy，and BMSCs transplantation with Rougan Huaxian Granules based on comprehensive medical treatment，respectively.Clinical response，pre- and post-treatment major TCM syndrome scores，liver function markers，prothrombin time，serum inflammatory cytokines，humoral and cellular immune markers，oxidative stress markers，and treatment-emergent adverse reactions and/or complications of the three groups were collected.Results　Finally，all the participants were included for analysis except 2 and 1 dropouts in groups A and B，respectively.Group C had significantly better clinical response than groups A and B，respectively（P<0.05）.The mean scores of hypochondriac pain，poor appetite，general lassitude and icterus in group C were significantly lower than those in groups A and B（P<0.05）.Group C had lower mean post-treatment serum levels of ALT，AST，total bilirubin，TNF-α，IL-2，IL-12，IgG，IgE and malondialdehyde，and CD8+ cell percentage，and significantly higher mean post-treatment levels of IFN-γ，IL-10，IgA，IgM，SOD and glutathione peroxidase，CD3+ cell percentage，CD4+ cell percentage and CD4+/CD8+ cell ratio，as well as significantly shorter mean prothrombin time than those in groups A and B（P<0.05）.There were 4 cases with complications in group A（3 with abdominal effusion，and 1 with gastrointestinal hemorrhage），and 2 cases with complications in group B（1 with hepatic encephalopathy and 1 with abdominal effusion），but no adverse reactions and/or complications occurred in group C.Conclusion　In treating patients with decompensated cirrhosis，Rougan Huaxian Granules combined with BMSCs could effectively relieve the clinical symptoms and signs，improve the liver function，coagulation and immune functions，and reduce the inflammatory and oxidative stress responses.

Key words: Liver cirrhosis, Mesenchymal stem cell transplantation, Rougan Huaxian Granules, Bone marrow mesenchymal stem cells, Inflammatory cytokines, Immune response, Oxidative stress

摘要： 背景　骨髓间充质干细胞（BMSCs）移植术为肝硬化患者带来了希望，但BMSCs在骨髓中含量极少且归巢能力有限，导致其临床应用受限。采用中医药招募内源性干细胞的动员方案可促进BMSCs归巢肝脏，对充分发挥中医药维持或改善机体正常再生修复作用具有重要意义。目的　探讨柔肝化纤颗粒联合BMSCs治疗肝硬化失代偿期的临床疗效及其对血清炎性因子水平、免疫功能、氧化应激反应的影响。方法　选取广西中医药大学第一附属医院肝病区及广西国际壮医医院脾胃肝病区2016年5月—2019年5月收治的肝硬化失代偿期患者120例，采用随机数字表法分为A组、B组和C组，每组40例。A组患者采用内科综合治疗，B组患者在内科综合治疗基础上进行1次BMSCs移植术并于术后给予长期抗病毒治疗1年，C组患者在内科综合治疗基础上采用柔肝化纤颗粒联合BMSCs移植术治疗。比较三组患者临床疗效和治疗前后主要中医证候评分、肝功能指标及凝血酶原时间（PT）、血清炎性因子水平、体液及细胞免疫功能指标、氧化应激反应指标，并记录患者三组患者治疗期间不良反应和/或并发症发生情况。结果　治疗期间A组2例患者脱落，B组1例患者脱落，最终A组、B组分别纳入38、39例患者。C组患者临床疗效优于A组、B组（P<0.05）。C组患者治疗后胁痛、纳差、神疲乏力、黄疸评分低于A组、B组（P<0.05）。C组患者治疗后血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBiL）、肿瘤坏死因子α（TNF-α）、白介素2（IL-2）、白介素12（IL-12）、免疫球蛋白G（IgG）、免疫球蛋白E（IgE）、丙二醛（MDA）水平及CD8+细胞分数低于A组、B组，血清干扰素γ（IFN-γ）、白介素10（IL-10）、免疫球蛋白A（IgA）、免疫球蛋白M（IgM）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）水平和CD3+、CD4+细胞分数及CD4+/CD8+细胞比值高于A组、B组，PT短于A组、B组（P<0.05）。A组患者治疗期间出现腹腔积液3例，消化道出血1例；B组患者治疗期间出现肝性脑病1例、腹腔积液1例；C组患者治疗期间无一例出现不良反应和/或并发症。结论　柔肝化纤颗粒联合BMSCs移植术可有效改善肝硬化失代偿期患者临床症状和体征、肝功能、凝血功能及免疫功能，减轻患者炎性反应及氧化应激反应。

关键词: 肝硬化, 间质干细胞移植, 柔肝化纤颗粒, 骨髓间充质干细胞, 炎性因子, 免疫应答, 氧化性应激

LYU Yanhang,WU Shanshan,WANG Zhenchang, et al. Clinical，Serum Inflammatory Cytokine，Immune，and Oxidative Stress Responses to Rougan Huaxian Granules with Transplantation of Bone Mesenchymal Stem Cells in Decompensated Cirrhosis Patients　[J]. Chinese General Practice, 2021, 24(3): 355-362. DOI: 10.12114/j.issn.1007-9572.2020.00.570.
吕艳杭,吴姗姗,王振常等. 柔肝化纤颗粒联合骨髓间充质干细胞移植术治疗肝硬化失代偿期的临床疗效及其对血清炎性因子水平和免疫功能及氧化应激反应的影响[J]. 中国全科医学, 2021, 24(3): 355-362. DOI: 10.12114/j.issn.1007-9572.2020.00.570.

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