摘要
目的探讨益气解毒颗粒对硫酸镍诱发大鼠鼻咽癌前病变的作用及其有关机制。方法40只健康雄性6周龄SD大鼠采用二亚硝基哌嗪和硫酸镍联合诱导鼻咽癌前病变模型,然后根据实验目的分为5组,每组8只。对照组先后给予0.9%氯化钠溶液3 d注射及42 d灌胃,模型组则给予100 mg·kg^(-1)·d^(-1)二亚硝基哌嗪注射和0.1 mg·kg^(-1)·d^(-1)硫酸镍灌胃,益气解毒颗粒低、中、高剂量组在模型组基础上分别给予0.5、2、8 g·kg^(-1)·d^(-1)益气解毒颗粒灌胃。苏木精-伊红染色观察SD大鼠鼻咽组织形态。免疫组化检测其鼻咽中ZMYND10、NF-κB的蛋白表达情况,实时荧光定量PCR检测其鼻咽中ZMYND10、NF-κB、Wnt-1和β-catenin的mRNA表达。结果与对照组相比,模型组大鼠鼻咽上皮癌前病变发生率显著升高,其NF-κB的mRNA和蛋白表达升高,ZMYND10的mRNA和蛋白表达降低,此外,Wnt-1和β-catenin的mRNA表达降低,差异均有统计学意义(P<0.05)。与模型组相比,益气解毒颗粒低、中、高剂量组大鼠鼻咽癌前病变发生率显著降低,NF-κB的mRNA和蛋白表达降低,ZMYND10的mRNA和蛋白表达升高,Wnt-1和β-catenin的mRNA表达升高,差异均有统计学意义(P<0.05),且对各指标影响均呈显著剂量依赖。结论益气解毒颗粒可显著抑制硫酸镍诱发的SD大鼠鼻咽癌前病变发生率,其机制主要通过调节Wnt/β-catenin通路、抑制NF-κB、增加ZMYND10的表达实现,且其作用效果呈显著剂量依赖。
Objective To investigate the effect and mechanism of Yiqi Jiedu Granules on nasopharyngeal precancerous lesions induced by nickel sulfate in rats.Methods Forty healthy male 6-week-old SD rats were combined with dinitrosopiperazine and nickel sulfate to induce nasopharyngeal precancerous lesions,then they were divided into 5 groups according to the purpose of the experiment,8 rats in each group.The control group was given a 3 d injection of saline followed by 42 d gavage.The model group was given 100 mg·kg^(-1)·d^(-1) dinitrosopiperazine injection and 0.1 mg·kg^(-1)·d^(-1) nickel sulfate gavage,and the low,medium and high dose groups were given low,medium and high doses(0.5,2,8 g·kg^(-1)·d^(-1))of Yiqi Jiedu Granules on the basis of the model group,and the nasopharyngeal tissue morphology of SD rats was observed using HE staining.The mRNA expressions of ZMYND10,NF-κB,Wnt-1 andβ-catenin in nasopharynx were detected by real-time fluorescence quantitative PCR,and the protein expressions of ZMYND10 and NF-κB in nasopharynx were detected by immunohistochemistry.Results Compared with the control group,the incidence of precancerous lesions of nasopharyngeal epithelium in the model group increased significantly,the expression of NF-κB mRNA and protein increased,and the expression of ZMYND10 mRNA and protein decreased,in addition,the expression of Wnt-1 andβ-catenin mRNA decreased,and the differences were statistically significant(P<0.05).Compared with the model group,the incidence of nasopharyngeal precancerous lesions in rats in the low,medium and high dose groups of Yiqi Jiedu Granules significantly decreased,the expressions of NF-κB mRNA and protein decreased,the expressions of ZMYND10 mRNA and protein increased,and the mRNA expression of Wnt-1 andβ-catenin increased,the differences were statistically significant(P<0.05),and there was a significant dose-dependent effect on each index.Conclusion In this study,Yiqi Jiedu Granules significantly inhibited the incidence of nasopharyngeal precancerous lesions induced by nickel sulfate in SD rats,and the mechanism was mainly achieved by Wnt/β-catenin signaling pathway via inhibiting NF-κB and increasing the expression of ZMYND10.And its effect is significantly dose-dependent.
作者
刘易婷
高英
景蓉
LIU Yi-ting;GAO Ying;JING Rong(Department of Oncology,Second Ward,Affiliated Hospital of Yan'an University,Yan'an Shaanxi 716000,China;Department of Nasopharyngology,Head and Neck Surgery,Affiliated Hospital of Yan'an University,Yan'an Shaanxi 716000,China)
出处
《临床和实验医学杂志》
2021年第19期2040-2044,共5页
Journal of Clinical and Experimental Medicine
基金
陕西省卫生健康科研基金项目(编号:2021B008)
延安市科技惠民计划项目(编号:2017HM-11-04)。
关键词
大鼠
益气解毒颗粒
硫酸镍
二亚硝基哌嗪
鼻咽癌
癌前病变
Rats
Yiqi Jiedu Granules
Nickel sulfate
Dinitropiperazine
Nasopharyngeal carcinoma
Precancerous lesions
