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*

doi:10.3969/j.issn.1672-5069.2024.04.019

摘要/Abstract

摘要： 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。

关键词: 肝硬化, 骨髓间充质干细胞移植术, 中药, 治疗

Abstract: 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-α and 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.

Key words: Liver cirrhosis, Bone marrow mesenchymal stem cells, Intrahepatic transplantation, Herbal medicine, Therapy

艾孜江·艾买提, 阿布都西库尔·阿布都米吉提, 迪丽努尔·阿卜杜热合曼, 吴源泉. 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^*[J]. 实用肝脏病杂志, 2024, 27(4): 567-570.

Aizijiang·Aimaiti, Abdusikul·Abdulmijiti, Dilinur· Abdulrahiman, et al. Clinical observation of bone marrow mesenchymal stem cell transplantation and herbal medicine in treatment of patients with decompensated cirrhosis[J]. Journal of Practical Hepatology, 2024, 27(4): 567-570.

参考文献

[1] Griemsmann M, Grote-Koska D, Cornberg M,et al. Plasma and ascites pharmacokinetics of meropenem in patients with decompensated cirrhosis and spontaneous bacterial peritonitis. J Hepatol,2022,76(1):230-233.
[2] Wentworth BJ, Haug RM, Northup PG,et al. Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis. Liver Int,2021,41(8):1913-1921.
[3] Wu Q, Mao W. New prognostic factor for hepatitis B virus-related decompensated cirrhosis: Ratio of monocytes to HDL-cholesterol. J Clin Lab Anal,2021,35(11):e24007.
[4] Mazhari S, Gitiara A, Baghaei K,et al. Therapeutic potential of bone marrow-derived mesenchymal stem cells and imatinib in a rat model of liver fibrosis. Eur J Pharmacol,2020,882(5):173263.
[5] Wang H, Lin C, Zhang X,et al. Mussel-inspired polydopamine coating: A general strategy to enhance osteogenic differentiation and osseointegration for diverse implants. ACS Appl Mater Interfaces,2019,11(7):7615-7625.
[6] Hu XJ,Li SX,Yang DX,et al.Modified gexiazhuyu decoction alleviates chronic salpingitis p38 signaling pathway.J Tradit Chin Med,2022,42(2):213-220.
[7] 中国中西医结合学会肝病专业委员会.肝纤维化中西医结合诊疗指南.中华肝脏病杂志,2006,14(11):866-870.
[8] Reynolds AS, Liang J, Raiss M,et al. Fatal cerebral edema in patients with decompensated cirrhosis: A case series. J Crit Care,2021,61(7):115-118.
[9] Hanafy AS, Abd-Elsalam S, Dawoud MM. Randomized controlled trial of rivaroxaban versus warfarin in the management of acute non-neoplastic portal vein thrombosis. Vascul Pharmacol,2019,113(7):86-91.
[10] Yu K, Huangfu H, Qin Q,et al. Application of bone marrow-derived macrophages combined with bone mesenchymal stem cells in dual-channel three-dimensional bioprinting scaffolds for early immune regulation and osteogenic induction in rat calvarial defects. ACS Appl Mater Interfaces,2022,14(41):47052-47065.
[11] Miceli V, Nigro AL, Pampalone M ,et al.Placenta-derived mesenchymal stem cells enhance human liver organoid maturation: translational implications for liver regeneration.Cytotherapy, 2020,22(5):96-97.
[12] Zhang DQ, Mu YP, Xu Y,et al.Research progress in Chinese medicine preparations for promoting blood circulation and removing blood stasis for cirrhotic patients with portal vein thrombosis following splenectomy.Chin J Integr Med.2022,28(9):855-863.
[13] Liu YM, Shi HB, Liu YR,et al. Protective effect of ganshuang granules on liver cirrhosis by suppressing regulatory T cells in mouse model. Chin J Integr Med, 2019,25(1):51-58.
[14] 吕艳杭,吴姗姗,温智稀,等.自拟中药动员骨髓间充质干细胞归巢治疗肝纤维化大鼠的机制研究.中华中医药学刊,2021,39(10):146-149.
[15] Lyu Y, Zhu T. Polyethyleneimine-modified porous aromatic framework and silane coupling agent grafted graphene oxide composite materials for determination of phenolic acids in Chinesewolfberry drink by HPLC.J Sep Sci,2020,43(4):774-781.
[16] Rao T, Gong YF, Peng JB,et al. Comparative pharmacokinetic study on three formulations of astragali radix by an LC-MS/MS method for determination of formononetin in human plasma.Biomed Chromatogr,2019,33(9):e4563.
[17] Chen Q, You X, Yang W,et al. Survival of endogenous hepatic stem/progenitor cells in liver tissues during liver cirrhosis. Life Sci,2020,241(15):117121.
[18] Cheng Y, Liu P, Hou TL,et al.Mechanisms of huangqi decoction granules on hepatitis B cirrhosis patients based on RNA-sequencing.Chin J Integr Med,2019,25(7):507-514.
[19] Dong BS, Liu FQ, Yang WN,et al. Huangqi decoction, a compound Chinese herbal medicine, inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-βaxis.J Integr Med,2023,21(1):47-61.
[20] Shu J, Jiang L, Wang M,et al. Human bone marrow mesenchymal stem cells-derived exosomes protect against nerve injury via regulating immune microenvironment in neonatal hypoxic-ischemic brain damage model. Immunobiology,2022,227(3):152178.
[21] Kumar M, Toprakhisar B, Haele M,et al. A fully defined matrix to support a pluripotent stem cell derived multi-cell-liver steatohepatitis and fibrosis model. Biomaterials,2021,276(14):121006.

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

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