实验性肝硬化大鼠肝组织中CSE和Ki-67的表达及其意义

实验性肝硬化大鼠肝组织中CSE和Ki-67的表达及其意义阎继攀;郑勇;刘浩;李睿;张宁;齐翠花;宋丽秀;陈卫刚

【摘要】目的应用正常及制备的肝硬化大鼠模型的肝脏组织观察H2S过载及不足状态下肝细胞的增殖变化.方法雌性SD大鼠48只,随机分为6组(每组8只):NF 组(正常对照组)、SF组(正常H2S增加组)、PF组(正常H2S减少组)、HF组(肝硬化对照组)、SHF组(肝硬化H2S增加组),PHF组(肝硬化H2S减少组).分组比较门静脉压力及门静脉血浆H2S含量,免疫组化法观察CSE及Ki-67的表达,免疫荧光双重染色观察CSE及Ki-67是否在同一细胞表达.结果随着给予H2S供体及H2S 的抑制剂,HF组H2S含量明显低于NF组(P＜0.01),SHF组和SF组中,给予H2S 供体均能使H2S含量升高(P＜0.01),给予H2S供体使H2S含量进一步升高(P＜0.01)；HF组CSE表达明显低于NF组(P＜0.01),SF组H2S表达较SHF组均减少(P＜0.01).H2S对正常大鼠无明显作用；HF组Ki-67表达明显高于NF组(P＜0.01),SF组H2S表达较SHF组增加(P＜0.01),Ki-67表达在正常大鼠无明显作用.结论 NaHS作为H2S供体可能具有抑制实验性肝硬化大鼠肝组织内细胞增殖的作用,H2S可能通过抑制星状细胞和肝血管平滑肌细胞从而对肝硬化起到保护作用.%Objective To observe the proliferation change of liver cells of experimental cirrhotic rats under excessive H2S environment and inadequate H2S environment. Methods All 48 female SD rats were randomly divided into the following 6 groups ( 8 per group) ; NF group ( normal control group ), SF group ( normal group with increasing H2S), PF group (normal group with decreasing H2S), HF group (cirrhosis group), SHF group (cirrhosis group with increasing H2S), PHF group (cirrhosis group with decreasing H2S). Portal venous pressure and the hydrogen

sulfide density in portal vein plasma among groups were compared; CSE and Ki-67 expression were observed by immunohisto-chemistry; CSE and Ki-67 expression in the same cell were observed by double immunofluorescence staining. Results With the supply of H2S donor and H2S inhibitors, H2S density of HF group became significantly lower than that of NF group (P<0.01). With the supply of H2S donor, H2S density of both HF group and NF group increased (P<0.01). With the increasing H2S density by increasing supply of H2S donor, CSE expression of HF group was significantly lower than that of NF group (P <0. 01 ) ; H2S expression of SF group was lower than that of SHF group (P<0.01);H2S had no significant effect on normal rats; Ki-67 expression of HF group was significantly higher than that of NF group (P < 0. 01 ) ; H2S expression of SF group was higher than that of SHF group (P <0. 01) ; Ki-67 expression had no significant effect on normal rats. Conclusion Acting as the H2S donor, HaHS probably inhibits cell proliferation in liver tissues of experimental cirrhotic rats; H2S probably plays a protective role in liver cirrhosis by inhibiting both hepatic stellate cells and vascular smooth muscle cells.

【期刊名称】《胃肠病学和肝病学杂志》

【年(卷),期】2012(021)003

【总页数】4页(P232-235)

【关键词】硫化氢;肝硬化;CSE;Ki-67;增殖

【作者】阎继攀;郑勇;刘浩;李睿;张宁;齐翠花;宋丽秀;陈卫刚

【作者单位】石河子大学医学院,新疆石河子832000;石河子大学医学院第一附属

医院消化内科,新疆石河子832000;石河子大学医学院,新疆石河子832000;石河子

大学医学院第一附属医院消化内科,新疆石河子832000;石河子大学医学院第一附

属医院消化内科,新疆石河子832000;石河子大学医学院第一附属医院消化内科,新

疆石河子832000;石河子大学医学院第一附属医院消化内科,新疆石河子832000;

石河子大学医学院第一附属医院消化内科,新疆石河子832000

【正文语种】中文

【中图分类】R575.2

内源性硫化氢(H2S)是继NO和CO之后发现的可以导致血管舒张的第3种气体信号分子［1］。内源性H2S产生依靠的两个关键性酶是CBS和CSE，CBS和CSE 在不同种属不同组织中的分布不同，据报道在哺乳动物的肝脏中以CBS为主［2］，本课题组前期研究提示H2S/CSE体系对门静脉高压的形成起抑制作用［3］，对

肝硬化起保护作用。Ki-67抗原是一种很好的增殖标物［4］。本实验应用免疫组

织化学方法分别检测实验性肝硬化大鼠CSE及Ki-67在肝脏细胞的表达，并用免

疫荧光双染法在同一张病理切片上检测CSE和Ki-67的表达，并探讨其表达的意义。

1 资料与方法

1.1 实验对象和分组雌性SD大鼠48只，均购自新疆维吾尔自治区医学实验动物

研究中心，随机分为6组(每组8只):NF组(正常对照组)、SF组(正常H2S增加组)、PF组(正常H2S减少组)、HF组(肝硬化对照组)、SHF组(肝硬化H2S增加组)，