摘要
目的观察益气温阳颗粒联合贝伐珠单抗对肺癌小鼠肿瘤组织微环境的影响。方法将50只C57BL/6J雄性小鼠随机分为5组,每组10只。模型组、贝伐珠单抗组、益气温阳组及贝伐珠单抗+益气温阳组小鼠于右腋窝皮下接种Lewis细胞,接种后3 d,贝伐珠单抗组给予贝伐珠单抗15 mg/kg腹腔注射(每周2次),益气温阳组给予20 g/kg的益气温阳粒生药灌胃(1次/d),贝伐珠单抗+益气温阳组给予贝伐珠单抗腹腔注射及益气温阳粒生药灌胃,正常组和模型组给予生理盐水灌胃。第14天给药2 h后处死小鼠,HE染色观察各造模组小鼠肿瘤组织病理学变化,免疫组化染色法检测肿瘤组织中低氧诱导因子1α(HIF-1α)的表达情况,Q-PCR法检测肿瘤组织中促红细胞生成素(EPO)和HK1 mRNA表达情况,ELISA法检测各组小鼠血清中转化生长因子β_(1)(TGF-β_(1))表达水平。结果贝伐珠单抗组肿瘤细胞变小,少量出血,大量凋亡,间质可见中度炎细胞浸润;益气温阳组肿瘤细胞团块状分布变小,偶有少量出血,可见小灶状细胞坏死及中度炎细胞浸润;贝伐珠单抗+益气温阳组肿瘤组织多处大片状坏死,肿瘤细胞显著减少,多处出血,大量炎细胞浸润。贝伐珠单抗组、贝伐珠单抗+益气温阳组小鼠肿瘤组织中HIF-1α表达IHS评分均明显低于模型组(P均<0.05),且贝伐珠单抗+益气温阳组明显低于益气温阳组(P<0.05),但与贝伐珠单抗组比较差异无统计学意义(P>0.05)。贝伐珠单抗组、益气温阳组及贝伐珠单抗+益气温阳组肿瘤组织中EPO mRNA相对表达量和血清TGF-β_(1)水平均明显低于模型组(P均<0.05),贝伐珠单抗组和贝伐珠单抗+益气温阳组均明显低于益气温阳组(P均<0.05),贝伐珠单抗组与贝伐珠单抗+益气温阳组比较差异无统计学意义(P均>0.05);贝伐珠单抗组和贝伐珠单抗+益气温阳组HK1mRNA相对表达量均明显低于模型组(P均<0.05),各药物组间两两比较差异均
Objective It is to observe the effects of Yiqi Wenyang granules combined with bevacizumab on tumor tissue microenvironment in mice with lung cancer.Methods Fifty male C57BL/6J mice were randomly divided into 5 groups,10 mice in each group.The mice in the model group,bevacizumab group,Yiqi Wenyang group and bevacizumab+Yiqi Wenyang group were inoculated with Lewis cells subcutaneously in the right axilla,and 3 days after inoculation,the bevacizumab group was given bevacizumab 15 mg/kg by intraperitoneal injection(twice per week),the Yiqi Wenyang group was given Yiqi Wenyang granules crude drug 20 g/kg by gavage(once per day),the bevacizumab+Yiqi Wenyang group was given bevacizumab by intraperitoneal injection and the crude drug of Yiqi Wenyang granules by gavage,and the normal group and model group were given normal saline by gavage.On the 14th day,the mice were sacrificed 2 hours after administration.The histopathological changes of the tumor tissues of the mice in each modeled group were observed by HE staining,and the expression of hypoxia-inducible factor 1α(HIF-1α)in the tumor tissues was detected by immunohistochemical staining,the expression of erythropoietin(EPO)and HK1 mRNA in tumor tissue was detected by Q-PCR method,the expression level of serum transforming growth factor β_(1)(TGF-β_(1))was detected by ELISA method.Results The tumor cells became smaller,with a little hemorrhage,a large amount of apoptosis,and moderate inflammatory cell infiltration in the interstitium in the bevacizumab group;the mass distribution of tumor cells became smaller,with occasional small amount of hemorrhage,small focal cell necrosis and moderate inflammatory cell infiltration in the Yiqi Wenyang group;the tumor tissue was necrotic in multiple large pieces,and the tumor cells were significantly reduced,with multiple hemorrhages and a large number of inflammatory cells infiltrated in the bevacizumab+Yiqi Wenyang group.The IHS scores of HIF-1αexpression in tumor tissues of mice in the bevacizumab group and bevacizumab+Yiq
作者
刘伟
谢莉莹
姜可园
梁绵杰
张慧婷
王雪玭
LIU Wei;XIE Liying;JIANG Keyuan;LIANG Mianjie;ZHANG Huiting;WANG Xuepin(The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China;Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China)
出处
《现代中西医结合杂志》
CAS
2022年第5期585-590,708,共7页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
天津市高等学校创新团队培养计划项目(TD13-5051)
国家自然科学基金资助项目(81603447)
天津市卫健委中医内科学十二五特色学科项目(20200402)。
关键词
肺癌
益气温阳颗粒
肿瘤微环境
贝伐珠单抗
lung cancer
Yiqi Wenyang granules
tumor microenvironment
bevacizumab
