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目的:探讨骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)移植治疗急性肝衰竭(acute liver failure,ALF)大鼠的疗效、移植途径.方法:用D-氨基半乳糖(D-galactosamine,D-GalN)/脂多糖(lipopolysaccharide,LPS)诱导大鼠ALF模型.72只大鼠随机分为ALF对照组、尾静脉移植组、门静脉移植组.于BMSCs移植后24、72、120、168 h取血清和肝组织,分别检测血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST);采用TUNEL法检测肝细胞凋亡;采用免疫组织化学、Western blot方法检测肝组织中半胱氨酸蛋白酶1(cysteinecontaining aspartate-specific proteases 1,Caspase1)和白介素18(interleukin-18,IL-18)蛋白的表达情况.结果:ALF对照组大鼠血清ALT、AST水平随病程逐渐升高.在移植后120、168 h,BMSCs移植组的血清ALT、AST与对照组相比差别有统计学意义(P<0.05);尾静脉、门静脉移植组细胞凋亡指数分别为28.17%±17.08%、20.67%±12.68%、19.67%±11.82%、13.00%±6.84%,与对照组相比差异有统计学意义(P<0.01).BMSCs移植组Caspase1、IL-18蛋白表达水平逐渐降低,在移植后120、168 h与对照组相比差异有统计学意义(P<0.05);且二者的表达有明显的相关性(P<0.01).尾静脉、门静脉移植途径对ALF大鼠均有治疗作用,但二种途径相比差异无统计学意义(P>0.05).结论:BMSCs能够改善ALF肝衰竭大鼠的肝功能,抑制肝细胞凋亡、降低Caspase1、IL-18蛋白水平.Caspase1和IL-18在肝衰竭的发病过程中起重要作用;Caspase1和IL-18可望成为急性肝衰竭的预测因子和未来的治疗靶点.
OBJECTIVE: To investigate the therapeutic effect and transplantation of bone marrow mesenchymal stem cells (BMSCs) transplantation in the treatment of acute liver failure (ALF) in rats.Methods: D-galactosamine D-GalN) / lipopolysaccharide (LPS) .All 72 rats were randomly divided into ALF control group, tail vein transplantation group and portal vein transplantation group.After 24, 72, 120, 168 h Serum and liver tissue were collected for detection of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), respectively. TUNEL assay was used to detect the apoptosis of hepatocytes. Immunohistochemistry and Western blot were used to detect the liver The expression of Caspase1 and IL-18 protein in the tissues of ALF control group.Results: The levels of ALT and AST in ALF control group gradually increased with the course of disease (P <0.05). The apoptotic indexes in the tail vein and portal vein transplantation group were significantly higher than those in the control group at 120 and 168 h posttransplantation 28.17% ± 17.08%, 20.67% ± 12.68%, 19.67% ± 11.82%, 13.00% ± 6.84%, respectively, there was significant difference compared with the control group (P <0.01) .The expression of Caspase1 and IL- (P <0.05), and there was a significant correlation between the two groups (P <0.01) .Tail vein and portal vein transplantation pathways (P> 0.05) .Conclusion: BMSCs can improve the liver function, inhibit the apoptosis of liver cells and decrease the expression of Caspase1 and IL-6 in ALF rats, 18 protein levels.Caspase1 and IL-18 play an important role in the pathogenesis of liver failure. Caspase1 and IL-18 are expected to become the predictors of future liver failure and future therapeutic targets.