脐血干细胞移植对失代偿期肝硬化患者TNF-α浓度和CD45RO+粒细胞表达的影响

Effect of umbilical cord blood stem cell transplantation on TNF-α concentration and the expression of CD45RO^+ and granulocyte in patients with decompensated liver cirrhosis

目的探究对失代偿期肝硬化患者进行脐血干细胞移植的临床疗效,并检测患者TNF-α浓度和CD45RO^+粒细胞表达的影响,为失代偿期肝硬化的诊治提供理论依据。方法回顾性分析2015年7月至2016年7月湖北医药学院附属人民医院消化内科治疗的80例失代偿期肝硬化患者。将40例在常规对症、支持治疗的基础加用通过肝动脉灌注性脐血干细胞移植治疗的患者设为观察组,40例常规治疗的患者设为对照组。比较患者治疗前与治疗后2个月、4个月、6个月肝功能总胆红素(TBIL)、谷丙转氨酶(ALT)、血清白蛋白(ALB)、谷草转氨酶(AST)水平,同时检测相关肝纤维化指标,包括层粘连蛋白(LN)、透明质酸酶(HA)、Ⅳ型胶原(ⅣCol)、Ⅲ型前胶原(ⅢNP),检测治疗前后肿瘤坏死因子(TNF-α)、白细胞介素6(IL-6)等细胞因子水平,并CD45RO^+淋巴细胞以及粒细胞表达水平。组间比较采用独立t检验。结果两组治疗后TBIL、ALT、AST水平低于治疗前(33.65±10.26)μmol/L vs(38.65±10.08)μmol/L,(56.76±14.27)U/L vs(64.23±14.56)U/L,(48.54±17.04)U/L vs(58.21±17.02)U/L,ALB高于治疗后(36.65±8.32)μg/L vs(32.56±8.12)μg/L,治疗后组间比较差异具有统计学意义(t=2.199、2.652、2.199、2.225,P=0.031、0.010、0.032、0.029);两组治疗后LN、HA、IVCol、IIINP低于治疗前(126.67±15.65)μg/L vs(143.65±15.21)μg/L,(231.67±34.43)μg/L vs(248.64±34.87)μg/L,(172.67±25.43)μg/L vs(188.67±26.56)μg/L,(32.54±5.43)μg/L vs(38.54±6.41)μg/L,且治疗后组间比较差异具有统计学意义(t=4.920、2.190、2.752、4.517;P=0.000、0.032、0.007、0.000);两组治疗后TNF-α、IL-6均逐渐降低(14.78±4.05)pg/ml vs(16.78±4.32)pg/ml,(15.87±6.05)pg/ml vs(19.09±6.12)pg/ml,且治疗后组间比较差异具有统计学意义(t=2.136、2.367;P=0.036、0.020);治疗后CD45RO^+淋巴细胞以及粒细胞表达水平均低于治疗前(22.54±3.65)% vs(25.11±3.38)% ,(22.54±6.54)% vs(25.54±6.37)% ,且组间比较差异具有统计学意义(t=3.267、2.078,P=0.002、0.041)。结论失代偿期肝硬化通过脐血干细胞移植治疗能够改善肝功能,降低相关肝纤维化指标,显著降低TNF-α、IL-6等细胞因子的水平以及CD45RO^+淋巴细胞以及粒细胞表达水平,可作为新型治疗失代偿期肝硬化有效方案。

Objective To investigate the clinical efficacy of umbilical cord blood stem cell transplantation on patients with decompensated liver cirrhosis and to detect the effect on TNF-α concentration and the expression of CD45RO＋ and granulocyte, so as to provide a theoretical basis for the diagnosis and treatment of decompensated cirrhosis. Method 80 patients with decompensated cirrhosis treated in the Dastroenterology Department of Affiliated Hospital of Hubei Medical College from July 2015 to July 2016 were selected and retrospectively analyzed. 40 patients in the observation group received umbilical cord blood stem cells transplantation through hepatic artery on the basis of symptomatic and supportive treatment, and 40 patients received routine treatment were included into control group. Liver function total bilirubin （TBIL）, glutamic-pyruvie transaminase （ALT）, serum albumin （ALB） and glutamic oxalacetie transaminase （AST） levels were compared before treatment, and 2 months, 4 months and 6 months after treatment. And the related indicators of hepatic fibrosis and cytokines levels were also detected, including laminin （LN）, hyaluronidase （HA）,IV type collagenase （ IV Col）, procollagen III （ III NP）, tumor necrosis factor （TNF-ct） and interleukin 6 （IL-6）. The expression levels of CD45RO~ lymphocyte and granulocyte were detected. Comparison between two groups was done with independent sample t-test. Results The postoperative TBIL, ALT and AST levels of two groups were significantly lower than those before treatment [（33.65±10.26） Ixmol/L vs （38.65± 10.08） btmol/L; （56.76± 14.27） U/L vs （64.23 ±14.56） U/L; （48.54±17.04） U/L vs （58.21 ± 17.02） U/L] ; While the postoperative ALB level was significantly higher than that before treatment [（36.65±8.32）/ag/L vs （32.56 ±8.12） μg/L] ; And the difference between the two groups after treatment was statistically significant （t = 2.199, 2.652, 2.199, 2.225, P = 0.031, 0.010, 0.032, 0.029）. The postoperative LN, HA, IV Col and III NP of two groups were significantly lower than those before treatment [（126.67± 15.65） g/L vs （143.65 ±5.21） g/L; （231.67±34.43） g/L vs （248.64±34.87） g/L; （172.67±25.43） g/L vs （188.67±26.56） g/L; （32.54 ±5.43） g/L vs （38.54±6.41） g/L]; And the difference between the two groups after treatment was also statistically significant （t = 4.920, 2.190, 2.752, 4.517; P = 0, 0.032, 0.007, 0）. TNF-ct and IL-6 decreased gradually after treatment in the two groups [（14.78±4.05） pg/ml vs （16.78 ±4.32） pg/ml; （15.87 ±6.05） pg/ml vs （19.09± 6.12） pg/ml ], and the difference was statistically significant after treatment （t = 2.136, 2.367; P = 0.036, 0.020）. The expression level of CD45RO~ lymphocyte and granulocyte after treatment was lower than that before treatment [ （22.54±3.65） % vs （25.11 ± 3.38） % ; （22.54± 6.54） % vs （25.54±-6.37） % ], and the difference between the groups was statistically significant （t = 3.267, 2.078, P = 0.002, 0.041）. Conclusion Application of umbilical cord blood stem cell transplantation for patients with decompensated liver cirrhosis can effectively ameliorate the liver function, and reduce the related indicators of liver fibrosis, the levels of TNF-α, IL-6 and other cytokines as well as CD45RO＋ lymphocytes and granulocyte expression levels. It can be used as a new effective treatment of decompensated cirrhosis.