摘要
目的探讨间充质干细胞(MSC)对急性肝功能衰竭(ALF)小鼠肝组织中miRNA-155和TNF表达的影响,以及与MSC疗效间的关系。方法采用随机数字表法和随机数余数分组法将BALB/c清洁级小鼠96只分为4组,即健康对照组、急性肝功能衰竭组、MSC治疗组和MSC预防组各24只。ALF组予以D—GaIN900mg/kg+脂多糖10μg/kg腹腔注射建立模型;MSC治疗组在900mg/kg D—GalN+10μg/kg脂多糖腹腔注射后2h,予以尾静脉注射MSC1×10^6;MSC预防组在900mg/kgDGalN+10ug/kg脂多糖腹腔注射前予以尾静脉注射MSCl×10^6;健康对照组予以0.9%氯化钠溶液1mL腹腔注射。给药7h后每组处死小鼠12只,检测小鼠血清肝功能,ELISA法检测TNF水平,实时定量PCR检测肝组织miRNA-155、TNFmRNA。余下每组12只小鼠观察24h生存率。组间均数比较用单因素方差分析,相关性分析采用Pearson和Spearman相关分析。结果胁GalN/脂多糖诱导7h后,MSC预防和MSC治疗组小鼠ALT水平均较ALF组降低,差异均有统计学意义(q值分别为13.20和4.58,均P〈0.01);MSC预防组和MSC治疗组AST水平均较ALF组降低,差异均有统计学意义(q值分别为18.90和9.83,均P〈0.01)。与ALF组相比,MSC预防组和MSC治疗组血清TNF水平均有所降低,差异均有统计学意义(q值分别为14.70和3.95,均P〈0.01)。健康对照组、ALF组、MSC治疗组和MSC预防组小鼠肝组织TNFmRNA表达水平分别为1.0±0.3、19.2±2.2、6.6±1.7和4.3±0.9,组间比较差异有统计学意义(F=72.24,P〈0.01)。与ALF组相比,MSC预防组和MSC治疗组小鼠肝组织TNFmRNA表达水平均有下调,差异均有统计学意义(q值分别为31.40和21.72,均P〈0.01)。与ALF组相比,MSC预防组和MSC治疗组小鼠肝组织miRNA-155水平均有下调,差异均有统计学意义(q值分别为19.40和9.58,均P〈0.01)。ALF组小鼠肝�
Objective To explore the effects of the mesenchymal stem cells (MSC) on the microRNA-155 (miRNA-155) and tumor necrosis factor (TNF) expressions in liver tissue of mice with acute liver failure (ALF), and to explore the relationship between miRNA-155/TNF and the efficacy of MSC. Methods Using a random number table method, and the remainder grouping method of random numbers. A total of 96 BALB/c mice of clean grade were randomly divided into four groups, namely groups of healthy control (intraperitoneal injection of 0.9% NaCI, 1 mid, ALF (intraperitoneal injection of Dgalactosamine (D-GaIN), 900 mg/kg body weight, and lipopolysaccharides, 10 mg/kg body weight), MSC treatment (1 ×10^6 MSC tail intravenously injected 2 h after intraperitoneal injection of D- GaIN and lipopolysaccharides) and MSC pretreatment (1×10^6 MSC tail intravenously injected before intraperitoneal injection of D GaIN and lipopolysaccharides). Twelve of the 24 mice in each group were sacrificed 7 h after intraperitoneal administration. Liver function, serum TNF level, miRNA-155 and TNF mRNA of liver tissue were detected subsequently. Survival rate at 24 h was observed in the remaining 12 mice in each group. Mean comparison between groups was conducted with ANOVA, and correlation analysis was performed using Pearson and Spearman correlation analysis. Results Seven hours after D GalN/lipopolysaccharides induction, alanine aminotransferase levels of MSC treatment and MSC pretreatment were significantly lower when compared with those of ALF (q=13.20 and 4.58, respectively; both P〈0.01); aspartate aminotransferase levels decreased in MSC treatment and MSC pretreatment groups compared to ALF group, with significant statistical differences (q 18. 90 and 9.83, respectively; both P〈0.01). Compared with ALF, serum levels of TNF decreased in MSC treatment and MSC pretreatment and the difference was statistically significant (q= 14. 70 and 3.95, respectively; both P〈0.01). The TNF mRNA expressions in li
出处
《中华传染病杂志》
CAS
CSCD
北大核心
2014年第1期2-6,共5页
Chinese Journal of Infectious Diseases