奥美拉唑对大鼠减体积肝移植后肝再生的影响

Effects of omeprazole on liver regeneration after reduced-size liver transplantation in rats

目的观察奥美拉唑对大鼠减体积肝移植肝细胞再生的影响。方法建立大鼠减体积肝移植模型,实验组移植后即时给予奥美拉唑,对照组予生理盐水。两组分别于肝移植术后分为5组(n=8),观察术后3、5、7、10、14 d血清丙氨酸转氨酶、天冬氨酸转氨酶值、移植肝重/供肝减体积前全肝重比值、移植肝细胞有丝分裂指数(MI)、增殖细胞核抗原(PCNA)表达指数、溴脱氧尿嘧啶核苷(BrdU)掺入指数及血清胃泌素值。结果大鼠减体积肝移植术后5 d肝细胞再生达高峰,实验组的再生活性显著高于对照组,MI为(2.54±0.24)%和(1.71±0.16)%(P<0.01)、PC- NA指数为(26.96±2.09)%和(18.73±1.94)%(P<0.01)、BrdU指数为(10.24±1.11)%和(5.75±0.88)%(P<0.01)。术后7 d,实验组和对照组移植肝重/全肝重比值分别为(76.3±1.6)%和(71.2±1.0)%(P<0.05),血清胃泌素水平分别为(441.9±25.9)ng/L和(292.9±14.2)ng/L(P<0.05)。术后14d,实验组和对照组移植肝重/全肝重比值分别为(94.5±1.7)%和(86.9±1.5)%(P<0.01),血清胃泌素水平分别为(487.8±29.4)ng/L和(291.7±21.6)ng/L (P<0.01)。实验组和对照组血清ALT、AST值差异无统计学意义。结论奥美拉唑能促进减体积肝移植术后的肝细胞再生,其作用可能与胃泌素分泌增高有关。

Objective To investigate the effects of omeprazole on liver regeneration after reduced-size liver transplantation in rats. Methods After reduced-size liver transplantation 80 rats were divided into two groups：experimental group and control group. The rats in experimental group and control group received omeprazole and NS respectively. In each group （ n = 8 ） , the liver function （ serum ALT, AST） ,the ratio of remnant liver weight vs total liver weight,the mitotic index （MI） of the transplanted livers,the proliferating cell nuclear antigen （PCNA） labeling index, the bromodeoxyuridine （BrdU） labeling index and the serum gastrin were determined 3,5,7,10 and 14 days after reduced-size liver transplantation. Results Hepatotoxicity of omeprazole has not been observed during the process of the experiments. Omeprazole significantly augmented MI, PCNA labeling index and BrdU labeling index of hepatocytes 5 days after transplantation （2.54 ± 0.24 ） % vs （ 1.71 ± 0.16 ） % （ P 〈 0.01 ）, （26.96±2.09 ） % vs （18.73±1.94）% （P〈0.01）,（10.24±1.11）% vs （5.75±0.88）% （P〈0.01） respectively. The ratio of remnant liver weight vs total liver weight and serum gastrin concentration in the experimental group were higher than those in control group one week after transplantation [ （76.3 ± 1.6）% vs （71.2 ± 1.0）% （P〈0.05） ,（441.9 ±25.9） ng/L vs （292.9 ± 14.2） ng/L （P 〈0.05） ] respectively and two weeks after transplantation [ （94.5 ± 1.7 ） % vs （86.9 ± 1.5 ） % （ P 〈 0.01 ）, （487.8 ± 29.4 ） ng/L vs （291.7 ± 21.6） ng/L （P 〈 0.01 ） ] respectively. Conclusion Omeprazole stimulates liver regeneration after reduced-size liver transplantation and this regeneration may be mediated by gastrin.