京尼平对ob/ob小鼠肝部分切除术后肝再生的影响

Effects of genipin on liver regeneration after partial hepatectomy in ob/ob mice

目的探讨瘦素基因遗传缺陷ob/ob小鼠肝部分切除术后肝再生功能的变化以及京尼平对其肝再生的影响。方法 20只ob/ob小鼠按处理方式不同随机分为京尼平组(ob G)和溶媒组(ob P),再依据肝切除术后时间的不同随机分为肝切除术(partial hepatectomy,PH)后2 d组和10 d组。C57BL/6J小鼠作为同期对照组。收集血清和肝脏标本。计算肝脏再生率;用免疫组织化学染色法检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)阳性表达率;用Feulgen染色法检测肝细胞DNA含量;用Western Blot法检测信号转导和转录活化因子3(signal transducer and activator of transcription 3,STAT3)的表达;血清生化检测肝功能指标。结果与C57BL/6J小鼠比较,ob/ob小鼠肝细胞内充满大小不等的脂滴、肝细胞气球样变及小灶性坏死;肝脏再生率(P<0.05)、PCNA阳性细胞数(P<0.01)和肝细胞DNA含量(P<0.01)显著降低。与溶媒组比较,京尼平组肝细胞病变减轻、双核肝细胞明显增多;肝脏再生率(P<0.05)、PCNA阳性细胞数(P<0.01)和肝细胞DNA含量(P<0.01)增高;血清ALT、AST、LDH水平降低(P<0.05);p-STAT3表达增加(P<0.05)。结论脂肪肝ob/ob小鼠肝部分切除术后肝再生延迟;京尼平可促进ob/ob小鼠的肝再生、改善肝功能。

Objective To investigate the changes of liver regeneration capacity after partial hepatectomy in ob/ob mice with leptin gene defect and the effects of genipin on their liver regeneration. Methods Twenty ob/ob mice were randomly divided into two groups： genipin（ ob G） and PBS groups（ ob P）. They were randomly divided into 2-and 10-d groups according to the time elapsed after hepatectomy. C57 BL/6 J mice served as a control group. Serum and liver samples were collected from the mice. The rate of liver regeneration was calculated,the rate of positivity for proliferating cell nuclear antigen（ PCNA） was determined by immunohistochemical staining,and the DNA content of hepatocytes was determined by Feulgen staining. Moreover,the expression of signal transducer and activator of transcription 3（ STAT3）was determined by Western blotting and liver function indicators were tested by serum biochemical method. Results Compared with those in C57 BL/6 J mice,the liver cells were filled with lipid droplets of varying sizes,and exhibited ballooning degeneration and focal necrosis in ob/ob mice; the liver regeneration rate（ P〈0. 05）,number of PCNApositive cells（ P〈0. 01）,and hepatocyte DNA content（ P〈0. 01） decreased significantly in the latter mice.Compared with the levels in the solvent group,the degree of hepatocytic lesions was reduced and the number of binucleated hepatocytes was significantly increased in the genipin group. In addition,the liver regeneration rate（ P〈0. 05）,number of PCNA-positive cells（ P〈0. 01）,and DNA content of hepatocytes（ P〈0. 01） in the genipin group were higher than those in the PBS group. The levels of ALT,AST,and LDH in the genipin group were lower than in the PBS group（ P〈0. 05）,while the expression of p-STAT3 in the genipin group was increased（ P〈0. 05）. Conclusions Fatty liver ob/ob mice exhibit delayed liver regeneration after partial hepatectomy. Genipin promotes liver regeneration and improves liver function in ob/ob mice.