中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (6): 1023-1026.doi: 10.3969/j.issn.1673-8225.2010.06.015

• 干细胞培养与分化 • 上一篇    下一篇

倒千里光碱对肝大部分切除小鼠肝脏损伤后再生修复的影响

廖芝玲1，陈加玲1，邝晓聪1，朱名毅1，黄英华1，蔡 捷2   

  1. 广西医科大学， 1病理生理学教研室，2医学实验中心，广西壮族自治区南宁市 530021
  • 出版日期:2010-02-05 发布日期:2010-02-05
  • 通讯作者: 邝晓聪，副教授，广西医科大学病理生理学教研室，广西壮族自治区南宁市 530021
  • 作者简介:廖芝玲，女，1963年生，广西壮族自治区岑溪县人，汉族，2007年广西医科大学毕业，博士，副教授，硕士生导师，主要从事肝癌分子病理学的研究。 liaozl1963@yahoo.com.cm 并列第一作者：陈加玲，女，1981年生，2009年广西医科大学毕业，硕士，主要从事肝脏干细胞的研究。
  • 基金资助:

    广西科技厅青年基金(桂科青0447026)；
    广西留学回国人员科学基金(桂科回0731016)

Retrorsine effects on regeneration and repair of injured liver in mice undergoing partial hepatectomy

Liao Zhi-ling1, Chen Jia-ling1, Kuang Xiao-cong1, Zhu Ming-yi1, Huang Ying-hua1, Cai Jie2   

  1. 1Department of Pathophysiology, 2Medical Experimental Center, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • Online:2010-02-05 Published:2010-02-05
  • Contact: Kuang Xiao-cong, Assoicate professor, Department of Pathophysiology, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • About author:Liao Zhi-ling, Doctor, Associate professor, Master’s supervisor, Department of Pathophysiology, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China Chen Jia-ling, Master, Department of Pathophysiology, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China Liao Zhi-ling and Chen Jia-ling contributed equally to the paper.
  • Supported by:

    the Youth Foundation of Department of Science and Technology of Guangxi Zhuang Autonomous Region, No. Guikeqing 0447026*;
    the Science Foundation of Returnees of Guangxi Zhuang Autonomous Region, No. Guikehui 0731016*

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460

被引次数

4

摘要：

背景：目前大多数应用倒千里光碱造成肝损伤模型都是以大鼠为实验对象，有研究报道倒千里光碱并不能抑制小鼠肝细胞增殖，也有报道倒千里光碱对小鼠的肝细胞具有增殖抑制作用。

目的：观察单纯肝脏大部分切除及其联合应用倒千里光碱致小白鼠对肝损伤后再生修复的影响。

方法：40只C57BL/6J小鼠随机数字表法分为2组，每组20只。倒千里光碱/肝脏部分切除组：腹腔注射倒千里光碱溶液70 mg/kg，注射2次，每次间隔2周，4周后肝脏2/3切除。肝脏部分切除组：腹腔注射生理盐水70 mg/kg，注射2次，每次间隔2周，4周后行肝脏2/3切除。观察术后14 d肝脏大体结构恢复情况；苏木精-伊红染色观察术后第3，7天肝细胞损伤情况；BrdU染色观察术后第3天成熟肝细胞增殖情况；CK19和C-kit免疫组织化学方法观察术后第3，7，14天肝脏卵圆细胞增生情况。

结果与结论：肝脏部分切除组14 d肝大体结构基本恢复正常，而倒千里光碱/肝脏部分切除组肝脏大小没有明显的恢复。苏木精-伊红染色可见倒千里光碱/肝脏部分切除组明显的肝细胞变性改变；BrdU染色肝脏部分切除组术后第3天有明显肝细胞增殖，而倒千里光碱/肝脏部分切除组肝细胞增殖很少。CK19和C-kit免疫组织化学结果显示倒千里光碱/肝脏部分切除组术后第3天开始肝脏主要通过肝卵圆细胞增生并逐渐向肝细胞和小胆管分化，从汇管区开始向肝小叶内延伸以修复损伤。提示倒千里光碱可抑制小鼠肝脏损伤后肝细胞增殖再生。建立倒千里光碱/肝脏部分切除小鼠模型可诱导肝脏卵圆干细胞增生。

关键词: 倒千里光碱, 肝大部分切除, 小鼠, 卵圆细胞, 肝再生, 肝脏干细胞

Abstract:

BACKGROUND: In many studies, rats were commonly used as models of retrorsine-induced hepatic injury. Some reports have confirmed that retrorsine cannot inhibit proliferation of mouse hepatic cells. Other reports have shown that retrorsine has inhibitory effects on proliferation of mouse hepatic cells.

OBJECTIVE: To study the liver regeneration after hepatic injury by creating mouse models treated with partial hepatectomy combination with retrorsine.

METHODS: A total of 40 C57BL/6J mice were equally and randomly assigned to 2 groups. In the partial hepatectomy combined with retrorsine group, intraperitoneal injection of retrorsine 70 mg/kg was conducted, twice, within an interval of 2 weeks. Four weeks later, 2/3 hepatectomy was performed. In the partial hepatectomy group, intraperitoneal injection of saline 70 mg/kg was performed, twice, with an interval of 2 weeks. Four weeks later, 2/3 hepatectomy was performed. At 14 days after partial hepatectomy, the restoration of the livers was observed. The liver cell injury was observed at 3, 7 days with hematoxylin-eosin staining. The hepatocyte proliferation was observed at 3 days with BrdU staining. Oval cell proliferation was observed at 3, 7and 14 days with CK19 and C-kit antibody immunohistochemistry.

RESULTS AND CONCLUSION: In the partial hepatectomy group, the damaged liver nearly restored to normal at 14 days after partial hepatectomy, and the result was contrary to partial hepatectomy combined with retrorsine group. Hematoxylin-eosin staining demonstrated that significant degeneration changes in hepatic cells in the partial hepatectomy combined with retrorsine group. BrdU staining showed that hepatocyte proliferation at day 3 was significantly determined in the partial hepatectomy group, but few in the partial hepatectomy combined with retrorsine group. CK19 and C-kit immunohistochemistry demonstrated that visible oval cell proliferation was seen in mice of partial hepatectomy combined with retrorsine group. First of all, hepatic oval cells appeared in portal area and differentiated into hepatic cells and bile duct cells, and then grew into the hepatic lobule gradually. These indicated that retrorsine can obviously inhibit hepatocyte regeneration after liver injury in mice. The model of mice treated with retrorsine and partial hepatectomy could induce oval cell proliferation.

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