肝气郁结对结肠癌模型小鼠肝转移的影响  

Effect of liver qi stagnationon liver metastasis of mouse model of colon cancer

作　　者：马梦雨[1] 杨晓燕[2] 赵璐[3] 梁芳[1] 张勇[1] 徐可[1] 樊瀛哲[1] 许建华[1] 

机构地区：[1]上海中医药大学附属普陀医院中医肿瘤科,博士研究生200062 [2]上海中医药大学附属普陀医院人事处,200062 [3]无锡市中医医院肿瘤科

出　　处：《环球中医药》2017年第6期682-686,共5页Global Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81573940);国家自然科学基金青年项目(81403350);上海市进一步加快中医药事业发展三年行动计划(中医药专门人才计划项目)(ZY3-RCPY-3-1012)

摘　　要：目的通过构建肝气郁结证模型,观察肝气郁结对结肠癌肝转移的影响并探讨β-AR信号通路在其中的作用机制。方法通过束缚制动法构建肝气郁结证模型,将BALB/C裸小鼠随机分为空白对照组、普萘洛尔对照组、ICI118,551对照组、空白肝郁组、普萘洛尔肝郁组、ICI118,551肝郁组,共六组,每组6只。ELISA法检测血清、脾种植瘤肾上腺素(epinephrine,E)、去甲肾上腺素(norepinephrine,NE)含量;qRT-PCR和Western blot法检测脾脏种植瘤组织转化生长因子-β(transforming growth factor-β,TGF-β)、白介素-6(interleukin-6,IL-6)、血管内皮生长因子(vascular endothelial growth factor,VEGF)和基质金属蛋白酶-9(matrix metalloprotein-9,MMP-9)表达情况;免疫组化法观察肝转移瘤组织VEGF和CD31蛋白表达情况。结果与空白对照组相比,空白肝郁组小鼠肝脏重量明显升高(P<0.01),并能升高小鼠血清NE、E水平及脾脏NE水平(P<0.01、P<0.05、P<0.05),差异具有统计学意义;与对照组相比,肝郁组小鼠脾脏肿瘤组织中TGF-β、IL-6、VEGF、MMP-9蛋白以及mRNA的表达显著升高(P<0.01),而给予普萘洛尔或ICI118,551后表达降低(P<0.01、P<0.05),差异具有统计学意义;肝郁组肝转移瘤VEGF、CD31表达明显高于对照组(P<0.01),给予普萘洛尔或ICI118,551后,则表达降低(P<0.01、P<0.05),差异有统计学意义。结论肝气郁结可通过介导β2-AR信号通路促进结肠癌肝转移。Objective The liver qi stagnation syndrome model was established to observe the effect of liver qi stagnation on liver metastasis of colon cancer and the role of β-AR signal pathway in it.Methods BALB/C mice were randomly divided into blank control group,propranolol control group,ICI118,551 control group,liver depression group,liver depression treated with propranolol group,liver depression treated with ICI118,551 group. The expressions of TGF-β,IL-6,VEGF and MMP-9 were detected by ELISA and Western blot. The expressions of VEGF and CD31 in liver metastatic tissues were observed by immunohistochemistry. Results Compared with the blank control group,the liver weight of the mice was significantly increased of liver depression group（ P〈0. 01）,and the level of NE and E in blood was increased（ P〈0. 01,P〈0. 05） and the level of NE in spleen was increased（ P〈0. 05）. The expression of TGF-β,IL-6,VEGF,MMP-9 and mRNA in spleen tumor of liver depression group was significantly higher than those of control group（ P〈0. 01）,and the expression was decreased after treated with propranolol or ICI118,551（ P〈0. 01,P〈0. 05）. The expression of VEGF and CD31 in liver metastases ofliver depression group was significantly higher than those in control group（ P〈0. 01）,and the expression was decreased after treated with propranolol or ICI118,551（ P〈0. 01,P〈0. 05）. Conclusion Liver qi stagnation can promote liver metastasis of colorectal carcinoma by mediating β2-AR signal pathway.

关 键 词：肝气郁结 结肠癌 肝转移 β-AR信号通路 

分 类 号：R285.5[医药卫生—中药学]