摘要
目的为了构建病证结合的小鼠模型及进行胃癌前病变(gastric precancerous lesions,GPL)脾胃虚实证候的本质研究。方法采用他莫昔芬(tamoxifen,TMXFR)诱导构建解痉多肽表达化生(spasmolytic peptide expression metagenesis,SPEM)小鼠模型,并在SPEM模型基础上分别模拟构建脾胃湿热证、脾气虚证模型,结合TMXFR诱导的SPEM模型具有自恢复的特性,以TMXFR组及生理盐水处理组作为对照组,监测小鼠一般情况,HE染色检测SPEM模型的构建及恢复情况,ELISA检测小鼠血清胃泌素水平,PCR检测各组小鼠胃黏膜中miR-7a-5p含量,免疫组化检测各组小鼠胃黏膜中白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-13(interleukin-13,IL-13)表达。结果病证结合的脾胃湿热证、脾气虚证组较TMXFR组、SPEM组织恢复明显延迟;脾胃湿热证较对照组及TMXFR组的胃泌素表达异常升高(P<0.05),SPEM模型组小鼠胃黏膜中miR-7a-5p较对照组水平降低(P<0.05),病证结合的脾胃虚实组miR-7a-5p表达较TMXFR有下降趋势;病证结合的脾胃虚实组IL-1β表达较TMXFR组、对照组升高(P<0.05),脾胃湿热证、脾气虚证组中IL-13表达有升高趋。结论此项研究结果侧面证实了在癌前病灶已形成的前提下,虽无幽门螺杆菌感染,在外感湿热之邪、进食肥甘厚腻、饥饱失常、过劳伤脾等诱因下,机体可突破自身代偿修复能力,延缓SPEM恢复甚至使GPL进一步进展。这可能跟miR-7a-5p介导炎症因子IL-1β使得Th1/Th2细胞失衡相关,但具体机制尚待进一步研究。
Objective To对照组struct a mouse model combining disease and syndrome and to study the essence of excess and deficiency syndrome of spleen and stomach of gastric precancerous lesions(GPL).Methods The mice model of spasmolytic polypeptide expressing metaplasia(SPEM)was induced by tamoxifen(TMXFR).Based on SPEM,the mice model with dampness-heat in spleen-stomach syndrome and spleen Qi deficiency syndrome were made separately.With the characteristics of reversibility of SPEM induced by TMXFR,the mice treated with saline were as the control group and the general situation of mice was monitored.Hematoxylin-eosin staining(HE)was used to measure SPEM and its recovery.ELISA was used to test the serum gastrin.The qRT-PCR method was used to test the expression of miR-7a-5p.The immunohistochemistry method was to test the expressions of interleukin-1β(IL-1β)and interleukin-13(IL-13).Results SPEM tissue was delayed the recovery in dampness-heat in spleen-stomach syndrome and spleen Qi deficiency syndrome significantly,the expression of gastrin in syndrome of spleen-stomach syndrome were higher than those in controll group and TMXFR group(P<0.05),and the expression of miR-7a-5p in the model group were lower than those in the controll group(P<0.05).The expression of IL-1βin dampness-heat in spleen-stomach syndrome and spleen Qi deficiency syndrome were higher than those in controll group and TMXFR group(P<0.05),and the expression of IL-13 had a trend of enhancement in the model group.Conclusion This study proves that on the pre condition of GPL,even if with no Helicobactor pylori infection,with evil of dampness and heat invasion,eating fat sweet and greasy,hunger,overfatigue hurting spleen,human dynamic equilibrium disturbed,which make SPEM delayed recovery and even progression for the SPEM.This study gives a clue that it is the result of miR-7a-5p mediating inflammatory cytokine IL-1β,making Th1/Th2 cytokine imbalance,but the specific mechanism should be explored deeply in the next research.
作者
陈万群
田锋亮
李延萍
张金卫
杨小军
CHEN Wanqun;TIAN Fengliang;LI Yanping;ZHANG Jinwei;YANG Xiaojun(Chongqing Hospital of Traditional Chinese Medicine,Chongqing 400000,China)
出处
《辽宁中医杂志》
CAS
北大核心
2024年第3期195-199,I0008,I0009,共7页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金青年项目(81904175)
重庆市技术创新与应用发展专项(CSTB2022TIAD-KPX0187)。
关键词
解痉多肽表达化生
胃癌前病变
脾胃湿热证
脾气虚证
病证结合
动物模型
spasmolytic polypeptide expressing metaplasia
gastric precancerous lesions
dampness-heat in spleen-stomach syndrome
spleen Qi deficiency syndrome
combination of disease and syndrome
mice model
