基于MMP-2、MMP-9探讨胃肠安方及其拆方抑制人胃癌裸鼠原位移植瘤生长及转移的部分配伍机制  

Compatibility mechanism of Weichang’an formula and its disassembled formulas in inhibiting the growth and metastasis of orthotopic transplanted human gastric cancer in nude mice based on MMP-2 and MMP-9 expression

作　　者：潘传芳[1] 梁未末[2] 顾贤[1] 沈克平[1] PAN Chuanfang;LIANG Weimo;GU Xian;SHEN Keping(The Fifth Department of Oncology,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Department of Dermatology,Huangpu District Hospital of Integrated Chinese and Western Medicine,Shanghai 200010,China)

机构地区：[1]上海中医药大学附属龙华医院肿瘤五科,上海200032 [2]上海市黄浦区中西医结合医院皮肤科,上海200010

出　　处：《上海中医药杂志》2020年第9期81-87,共7页Shanghai Journal of Traditional Chinese Medicine

基　　金：上海市教委资助项目(06CZ003);国家中医药管理局第六批全国老中医药专家学术经验继承工作项目[国中医药人教发(2017)29号]。

摘　　要：目的通过体内研究探讨胃肠安方及其不同功效组成药物拆方对胃癌裸鼠原位移植瘤生长及转移作用效果及其配伍规律。方法将胃肠安方按其功效拆分为健脾理气、清热解毒、软坚散结三大组成部分,采用2×2×2析因实验设计方案,建立裸小鼠人胃癌原位移植模型。观察胃肠安方不同功效组成药物抑制胃癌生长及转移作用效果及其之间是否存在交互作用。结果①胃肠安方全方组及健脾理气组、软坚散结组、健脾清热组的抑瘤率分别为28.5%、24.6%、28.8%及30.2%,与模型组瘤重比较明显下降,差异有统计学意义(P<0.05);软坚散结因素在抑制瘤重方面具有主效应,健脾理气及软坚散结因素存在交互作用。②胃肠安全方组、清热解毒组、健脾清热组的转移率分别为22.22%、10.00%、18.18%,与模型组75.00%比较,能明显降低裸鼠胃肿瘤的转移率(P<0.05)。③胃肠安全方组及其不同治则拆方配伍各组中除软坚散结组外,均能抑制MMP-2蛋白表达,尤其以健脾理气组及全方组作用最为明显(P<0.05);健脾组、健脾清热组及全方组对MMP-9蛋白表达抑制作用最为明显(P<0.05)。析因分析结果显示,在软坚散结因素存在时,健脾理气因素与清热解毒因素在下调MMP-2蛋白表达方面具有协同作用。胃肠安方及其拆方对裸鼠胃肿瘤组织MMP-2基因表达具有不同程度的抑制作用,以全方组、健脾软坚组、清热软坚组作用最为明显(P<0.01)。析因分析结果显示,健脾理气与清热解毒及清热解毒与软坚散结组之间对MMP-2的基因表达抑制具有相互交互作用。全方组、健脾软坚组对裸鼠胃肿瘤组织MMP-9 mRNA表达抑制作用明显(P<0.01),健脾理气与清热解毒及健脾理气与软坚散结组对MMP-9 mRNA表达抑制具有相互交互作用。胃肠安方全方组及健脾理气组明显抑制裸鼠胃肿瘤组织MMP-2及MMP-9的活性(P<0.01),析因分析结果显示,在清热解毒�Objective To explore the effects and compatibility regularity of Weichang’an recipe(WCAR)and its disassembled recipes with different efficacious components on the growth and metastasis of orthotopic transplanted tumor in nude mice with gastric cancer in vivo.Methods According to its efficacy,WCAR was divided into three components:Jianpi Liqi(JPLQ,invigorating spleen and regulating qi),Qinre Jiedu(QRJD,clearing away heat and removing toxin)and Ruanjian Sanjie(RJSJ,softening hardness and dissipating mass).A 2*2*2 factorial experiment was designed to establish an orthotopic transplantation model of human gastric cancer in nude mice and to observe the effects of different effective components of WCAR on inhibiting the growth and metastasis of gastric cancer and whether there is interaction between them.Results①The tumor inhibition rates of the WCAR group,the JPLQ group,the RJSJ group and the Jianpi Qingre(JPQR,invigorating spleen and clearing away heat)group were 28.5%,24.6%,28.8%and 30.2%,respectively.The tumor weight in these groups were significantly reduced compared with the model group(P<0.05).The factor of the RJSJ had the main effect in inhibiting the weight of tumor,and there was an interaction between the JPLQ factor and the RJSJ factor.②The metastasis rates of the WCAR group,QRJD group and JPQR group were 22.22%,10.00%and 18.18%respectively,which were obviously reduce the metastasis rate of gastric cancer in nude mice compared with 75%of model control group(P<0.05).③The expression of MMP-2 protein was inhibited in the WCAF group and its disassembled recipe groups except the RJSJ group,especially in the JPLQ group and the WCAR group(P<0.05).There was the most obvious inhibitory effect on the expression of MMP-9 protein in the Jianpi(JP,invigorating spleen)group,JPQR group and WCAR group(P<0.05).The results of factorial analysis showed that in the presence of RJSJ factor,the factors of JPLQ and QRJD had a synergistic effect on down-regulating the expression of MMP-2 protein.The WCAF and its disassembl

关 键 词：胃肠安方 配伍研究 胃癌 MMP-2 MMP-9 肿瘤转移 小鼠 

分 类 号：R285.5[医药卫生—中药学]