非酒精性脂肪肝大鼠部分肝切除术后肝再生功能的变化

目的 探讨大鼠非酒精性脂肪肝（NAFLD）部分肝脏切除术后肝再生功能的变化。方法 80只Wistar大鼠，随机分为正常对照组（C组，35只）与NAFLD组（F组，45只），C组给予正常饮食喂养，F组给予高脂饲料喂养。在喂养至第12周时行70％肝切除术，两组动物分别于术后0、1、12、24、36h处死，取出残肝，计算再生肝重比；光镜下计数核分裂肝细胞；透射电镜观察术后肝细胞超微结构的变化；免疫组织化学染色法检测增殖细胞核抗原阳性表达率；半定量逆转录聚合酶链反应检测细胞周期蛋白D1的表达变化。结果 光镜和电镜观察显示F组肝窦狭窄迂曲，细胞质内大量脂滴沉积，细胞核小，细胞器少，能量代谢及细胞增殖均不活跃。F组术后12、24、36h核分裂相计数明显低于C组同时相点（P〈0．01）；F组术后再生肝重比、S期细胞分数及增殖指数也较C组下降，差异有统计学意义（P〈0．01）；F组增殖细胞核抗原阳性率、细胞周期蛋白D1的mRNA表达在术后12、24、36h均明显低于C组同时相点（P〈0．01）。结论 中至重度NAFLD大鼠部分肝切除术后DNA合成高峰滞后，肝再生延迟，再生进程主要被阻滞在细胞周期的G1／S期调控点。

Liver regenerative capacity after partial hepatectomy in rats with nonalcoholic fatty liver disease

OBJECTIVE: To explore the changes of liver regeneration after partial hepatectomy on rats with nonalcoholic fatty liver disease (NAFLD) caused by a high fat diet. METHODS: One hundred Wistar rats were randomly divided into a control group (group C, n = 45), fed with normal diet, and a NAFLD group, fed with fat-rich diet (group F, n = 55). All rats had a 70% partial hepatectomy at the end of the 12th week. They were sacrificed at postoperative 0, 1, 12, 24, or 36 hours and the percentages of their regenerated liver masses were calculated. The mitosis index was measured microscopically and the changes of cell ultrastructure were observed under an electron microscope. The expression of proliferating cell nuclear antigen (PCNA) was detected using immunohistochemistry. The expression of mRNA of cyclin D1 was measured by RT-PCR. RESULTS: The light and electron microscopy showed that the hepatic sinusoids expanded at an early period after the partial hepatectomy. The mitochondria and rough endoplasmic reticulum (RER) expanded and their number increased. The mitosis index was increased. The sinusoids of the livers in group F were narrow and irregular. The nuclei were smaller and the necrotic cells increased. As compared with the control group, the mitosis index was significantly decreased (P < 0.01), and the regenerative liver weight ratio in group F was lower at postoperative 12 h, 24 h, 36 h (P < 0.01). PCNA labeling index in group F also was lower than that in group C. The peak of the PCNA in group F was later than that of the control group (P < 0.01). In group C, the mRNA of cyclin D1 peaked at the 24th hour after the partial hepatectomy, and then decreased afterwards. In group F, it was lower than that of group C at the same time (P < 0.01). CONCLUSION: After NAFLD rats had partial hepatectomies, the capacity of their liver regeneration decreased and the peak of DNA synthesis was delayed, and at the same time the morbidity of the rats increased.