骨髓间充质干细胞移植联合自拟中药治疗失代偿期肝硬化患者效果研究

Clinical observation of bone marrow mesenchymal stem cell transplantation and herbal medicine in treatment of patients with decompensated cirrhosis

目的探讨骨髓间充质干细胞(BMSCs)移植术联合自拟中药治疗失代偿期肝硬化患者的效果。方法2017年6月~2022年10月我院收治的93例失代偿期肝硬化患者,随机分为A组、B组和C组,每组31例。给予A组常规内科综合治疗,在此基础上,给予B组自体BMSCs移植术治疗,C组在BMSCs移植术后,给予自拟中药治疗,三组均治疗观察6个月。采用放射免疫分析法检测血清透明质酸(HA)、IV型胶原(CIV)、层粘连蛋白(LN)和III型前胶原(PIIIP)水平;采用ELISA法检测血清白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平;分别采用黄嘌呤氧化酶法和硫代巴比妥法检测血清超氧化物歧化酶(SOD)和丙二醛(MDA)水平。结果在治疗6个月末,C组Child-Pugh评分和肝硬度测量(LSM)分别为(7.2±1.2)分和(9.0±0.6)kPa,显著低于B组【分别为(8.0±1.1)分和(9.3±0.5)kPa,P<0.05】或A组【分别为(8.9±1.4)分和(9.6±0.6)kPa,P<0.05】,而血清ALB水平为(34.6±3.1)g/L,显著高于B组【(32.0±1.9)g/L,P<0.05】或A组【(30.8±2.4)g/L,P<0.05】;C组血清HA和LN水平分别为(123.8±31.8)ng/mL和(112.9±27.5)ng/mL,显著低于B组【分别为(141.7±29.5)ng/mL和(129.3±30.3)ng/mL,P<0.05】或A组【分别为(186.2±36.7)ng/mL和(161.1±36.5)ng/mL,P<0.05】;C组血清IL-6、TNF-α和MDA水平分别为(104.6±16.7)ng/L、(192.7±19.8)ng/L和(4.1±0.9)μmol/L,显著低于B组【分别为(114.3±15.3)ng/L、(210.9±22.8)ng/L和(5.0±1.3)μmol/L,P<0.05】或A组【分别为(132.8±19.5)ng/L、(230.2±27.1)ng/L和(6.2±1.5)μmol/L,P<0.05】,而血清SOD水平为(143.9±14.5)U/mL,显著高于B组【(134.2±13.3)U/mL,P<0.05】或A组【(122.1±11.7)U/mL,P<0.05】。结论采用BMSCs移植术联合自拟中药治疗失代偿期肝硬化患者可改善肝功能指标,可能与抑制了炎性反应和缓解了氧化应激反应有关。

Objective The aim of this study was to observe the efficacy of bone marrow mesenchymal stem cell(BMSC)transplantation and herbal medicine in treatment of patients with decompensated cirrhosis.Methods A total of 93 patients with decompensated cirrhosis were encountered in our hospital between June 2017 and October 2022,and were randomly divided into group A,group B and group C.The patients in the group A were dealt with comprehensive internal medicines,and those in the group B received BMSC transplantation and the patients in the group C were treated with BMSC transplantation and thereafter herbal medicine therapy for six months.Serum hyaluronic acid(HA),type-IV collagen(CIV),laminin(LN)and type-III precollagen(PIIIP)levels were detected by radioimmunoassay,and serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)levels were detected by ELISA.Serum superoxide dismutase(SOD)and malondialdehyde(MDA)levels were detected by xanthine oxidase method and thiobarbituric acid method.Results At the end of 6 month treatment,the Child-Pugh score and liver stiffness measurement(LSM)in group C were(7.2±1.2)and(9.0±0.6)kPa,both significantly lower than[(8.0±1.1)and(9.3±0.5)kPa,P<0.05]in group B or[(8.9±1.4)and(9.6±0.6)kPa,P<0.05]in group A,while serum albumin level was(34.6±3.1)g/L,much higher than[(32.0±1.9)g/L,P<0.05]in group B or[(30.8±2.4)g/L,P<0.05]in group A;serum HA and LN levels were(123.8±31.8)ng/mL and(112.9±27.5)ng/mL,both significantly lower than[(141.7±29.5)ng/mL and(129.3±30.3)ng/mL,P<0.05]in group B or[(186.2±36.7)ng/mL and(161.1±36.5)ng/mL,P<0.05]in group A;serum IL-6,TNF-αand MDA levels were(104.6±16.7)ng/L,(192.7±19.8)ng/L and(4.1±0.9)μmol/L,all significantly lower than[(114.3±15.3)ng/L,(210.9±22.8)ng/L and(5.0±1.3)μmol/L,P<0.05]in group B or[(132.8±19.5)ng/L,(230.2±27.1)ng/L and(6.2±1.5)μmol/L,P<0.05]in group A,while serum SOD level was(143.9±14.5)U/mL,significantly higher than[(134.2±13.3)U/mL,P<0.05]in group B or[(122.1±11.7)U/mL,P<0.05]in group A.Conclusion The BMSC transplantation followed by herbal medicine in treatment of patients with decompensated liver cirrhosis could alleviate liver fibrosis and improve liver functions,which might be related to the inhibition of inflammatory cytokines and oxidative stress response.