微囊化肝细胞移植对急性肝功能衰竭大鼠细胞因子的影响

目的 观察微囊化肝细胞移植对急性肝功能衰竭(ALF)大鼠脂多糖(LPS)、TNF-α、IL-1β和IL-6的影响.方法 用D-氨基半乳糖诱导大鼠ALF模型.造模后18 h,60只大鼠均分为模型组、裸肝细胞移植组和微囊化肝细胞移植组,72 h取血标本,检测血常规、Cr、肝功能、PT和血氨;鲎试剂检测LPS;ELISA法检测TNF-α、IL-1β和IL-6.多组比较采用单因素方差分析.结果 裸肝细胞移植组和微囊化肝细胞移植组大鼠Cr、肝功能、PT及血氨较模型组有明显改善(P<0.01),且微囊化肝细胞移植组较裸肝细胞移植组改善更明显,差异有统计学意义(P<0.01).裸肝细胞移植组和微囊化肝细胞移植组LPS为(1.2±0.3)和(0.5±0.1)ng/L,TNF-α为(27.7α4.2)和(21.7±3.2)μg/L,IL-1β为(298.7±13.9)和(247.7±14.1)ng/L,IL-6为(275.7±51.8)和(208.7±48.1)ng/L;模型组分别为(2.1±0.6)ng/L、(37.7±5.1)μg/L、(355.5±26.4)ng/L和(424.8±67.8)ng/L,裸肝细胞移植组LPS、TNF-α、IL-1β、IL-6与模型组比较,差异有统计学意义(F=6.24,F=67.3,F=8.38,F=7.59,均P<0.01);微囊化肝细胞移植组与模型组比较,差异亦有统计学意义(F=11.73,F=10.75,F=15.91,F=10.83,均P<0.01);微囊化肝细胞移植组与裸肝细胞移植组比较,差异亦有统计学意义(F=5.49,F=4.01,F=7.53,F=3.35,均P<0.01).结论 微囊化肝细胞移植可通过降低LPS、TNF-α、IL-1β及IL-6而发挥抗ALF的作用.

Effects of microencapsulated hepatocytes transplantation on cytokines in rats with acute liver failure

Objective To evaluate the effects of microencapsulated hepatocyte transplantation on lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in rats with acute liver fallure (ALF). Methods The rat model of ALF was induced by D-galactosamine and the rats were divided into 3 groups after 18 h of injection: model group (n=20); free hepatocytetransplantation group (n=20); microencapsu|ated hepatocyte transplantation group (n=20). The samples of blood and liver tissue at 72 h were collected. Blood routine, creatinine, liver function, prothrombin time (PT), blood ammonia were detected. LPS was tested using tachypleus amebocyte lysate, Levels of TNF-α, IL-1β and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA). Comparison among groups was done by one way ANOVA. Results Creatinine, liver function, PT and blood ammonia were all obviously improved in free hepatocyte transplantation group and microencapsulated hepatocyte transplantation group than model group (P<0.01), and those in microencapsulated hepatocyte transplantation group were improved significantly than those in free hepatocyte transplantation group (P<0.01). In free hepatocyte transplantation group and microencapsulated hepatocyte transplantation group, LPS levels were (1.2±0.3) ng/L and (0.5±0.1) ng/L, respectively; TNF-α were (27.7±4.2)μg/L and (21.7μ3.2)μg/L, respectively; IL-1βwere (298.7±13.9)ng/L and (247.7±14.1) ng/L, respectively; IL-6 were (275.7±51.8) ng/L and (208.7±48.1)ng/L, respectively. The levels of LPS, TNF-α, IL-1β and IL-6 were (2.1±0.6)ng/L, (37.7±5.1)μg/L, (355.5±26.4)ng/L and (424.8/±67.8)ng/L, respectively in model group. The levels of LPS, TNF-a, IL-1β and IL-6 in free hepatocyte transplantation group were all significantly different from those in model group (F=6. 24, F=6. 73, F=8. 38, F=7. 59, respectively, all P<0.01); those in microencapsulated hepatocyte transplantation group were significantly different from those in model group (F=11.73, F=10. 75, F=15.91, F=10. 83, respectively, all P<0.01) and in free hepatocyte transplantation group (F=5.49, F=4.01, F= 7.53, F=3.35, respectively, all P < 0.01). Conclusion Microencapsulated hepatocyte transplantation can play anti-ALF role through reducing levels of LPS, TNF-α, IL-1β and IL-6.