机构地区:[1]韶关市中医院药学部,广东韶关512026 [2]深圳市龙华区人民医院药学部,广东深圳518109 [3]广州华腾生物医药科技有限公司,广州510700
出 处:《中国处方药》2025年第3期24-28,共5页Journal of China Prescription Drug
摘 要:目的探讨基于能量抑制的“扶正祛邪”中药参芪扶正注射液联合紫杉醇对肺癌耐药的影响及作用机制。方法将20只Balb/c裸鼠随机分为模型阴性对照组、模型阳性对照组及参芪扶正低、中、高剂量组,每组4只,皮下接种卡铂耐药A549细胞株。待皮下瘤长径长至5~7 mm后,除模型阴性对照组外的其余各组均尾静脉注射紫杉醇(10 mg/kg)+卡铂(6 mg/kg),每3天1次,参芪扶正低、中、高剂量组每日静脉注射0.1、0.2、0.4 ml参芪扶正注射液。干预14 d后,测量肿瘤大小、质量,HE、TUNEL染色观察肿瘤病理情况,Western blot和RT-qPCR实验分别检测肿瘤组织中P-糖蛋白(P-gp)、低密度脂蛋白受体相关蛋白1(LRP1)、血清基质金属蛋白酶9(MMP-9)蛋白、基因表达情况。结果与模型阴性对照组比较,参芪扶正高剂量组第9、12、14 d的皮下瘤体积和皮下瘤质量均降低(P<0.05);与模型阴性对照组比较,模型阳性对照组及各参芪扶正干预组肿瘤组织病理情况显示不同程度好转;模型阴性对照组的TUNEL染色阳性细胞率为(0.58±0.10)%,与其比较,参芪扶正低、中、高剂量组TUNEL染色阳性细胞率均升高,分别为(1.25±0.27)%、(1.63±0.34)%、(2.80±0.49)%(P<0.05),且参芪扶正高剂量组高于模型阳性对照组和参芪扶正低、中剂量组(P<0.05);参芪扶正中、高剂量组P-gp、LRP1、MMP-9相对蛋白表达水平与模型阴性对照组相比均降低,且参芪扶正高剂量组低于模型阳性对照组和参芪扶正低、中剂量组(P<0.05);参芪扶正中、高剂量组P-gp、LRP1、MMP-9的mRNA相对表达水平与模型阴性对照组相比下调,参芪扶正低剂量组LRP1的m RNA相对表达水平低于模型阴性对照组(P<0.05),且参芪扶正高剂量组低于模型阳性对照组和参芪扶正低、中剂量组(P<0.05)。结论中药参芪扶正注射液通过抑制细胞凋亡及影响耐药相关蛋白的表达,可能在一定程度上克服肺癌的耐药性,并促进�Objective To explore the influence and role mechanism of“Fuzheng Quxie”traditional Chinese medicine Shenqi Fuzheng Injection based on energy inhibition combined with paclitaxel on drug resistance of lung cancer.Methods Twenty Balb/c nude mice were randomly divided into model negative control group,model positive control group and low-,medium-and high-dose Shenqi Fuzheng groups,with 4 mice in each group.Carboplatin-resistant A549 cell lines were subcutaneously inoculated.After the subcutaneous tumor grew to 5-7 mm in length,except for the model negative control group,the other groups needed tail vein injection of paclitaxel(10 mg/kg)combined with carboplatin(6 mg/kg),once every 3 days.Low-,medium-and high-dose Shenqi Fuzheng groups were intravenously injected with 0.1,0.2 and 0.4 ml Shenqi Fuzheng Injection daily.After 14 days of intervention,tumor size and mass were measured.HE and TUNEL staining methods were used to observe tumor pathological conditions.Western blot and RT-qPCR were applied to detect the protein and gene expressions of P-glycoprotein(P-gp),low density lipoprotein receptorrelated protein 1(LRP1),serum matrix metalloproteinase 9(MMP-9)in tumor tissues.Results Compared with model negative control group,the subcutaneous tumor volume and mass in high-dose Shenqi Fuzheng group were decreased on the 9th day,12th day and 14th day(P<0.05),and the pathological conditions of tumor tissues in model positive control group and Shenqi Fuzheng intervention groups were improved to varying degrees.Compared with(0.58±0.10)%in model negative control group,the TUNEL staining positive cell rate in low-,medium-and high-dose Shenqi Fuzheng groups was increased[(1.25±0.27)%,(1.63±0.34)%and(2.80±0.49)%](P<0.05),and the positive cell rate in highdose Shenqi Fuzheng group was higher than that in model positive control group and low-and medium-dose Shenqi Fuzheng groups(P<0.05).Compared with the model negative control group,the relative protein expression levels of P-gp,LRP1 and MMP-9 in medium and high-dose Shenqi
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