赤芍总苷对肺癌模型大鼠抑癌相关基因表达的影响

Effects of Total Paeony Glycoside on the Expression of Tumor Suppressor Gene in Lung Cancer Model Rats

目的:研究赤芍总苷对肺癌模型大鼠抑癌相关基因表达的影响。方法:将90只大鼠随机分为正常组、模型组、阳性对照组[环磷酰胺,50 mg/(kg·d)]和赤芍总苷低、中、高剂量组[50、100、200 mg/(kg·d)],每组15只。除正常组外,其余各组大鼠均采用左肺叶支气管内一次性灌注致癌碘油液复制肺癌模型,造模成功后,每周周一至周五各组大鼠于背iv相应药物,正常组和模型组iv等体积生理盐水,连续16周。采用逆转录-聚合酶链反应法测定大鼠肺组织中多药耐药相关蛋白(MRP)、人多药耐药基因(MDR1)和凋亡相关基因P21、P16 m RNA的表达;采用免疫组化法测定肺组织中抑癌基因P53蛋白的表达,计算其阳性率;观察肺组织病理变化。结果:与正常组比较,模型组大鼠肺组织中MRP、MDR1、P21、P16 m RNA及P53蛋白表达(阳性率为66.67%)水平明显升高(P<0.05);与模型组比较,阳性对照组和赤芍总苷低、中、高剂量组大鼠肺组织中MRP、MDR1、P21、P16 m RNA及P53蛋白表达(阳性率分别为46.67%、46.67%、40.00%、13.33%)水平降低并呈剂量依赖性,且赤芍总苷中、高剂量组比阳性对照组降低程度更显著(P<0.05);赤芍总苷各剂量组间比较,各指标差异均有统计学意义(P<0.05)。结论:赤芍总苷可明显抑制肺癌模型大鼠MRP、MDR1、P21、P16基因及P53蛋白的表达。

OBJECTIVE：To investigate the effects of total paeony glycoside（TPG） on the expression of tumor suppressor gene in lung cancer model rats.METHODS：90 rats were randomly divided into normal group,model group,positive control group [cyclophosphamide,50 mg/（kg·d）] and TPG low-dose,medium-dose and high-dose groups [50,100,200 mg/（kg·d）] with15 rates in each group.Except for normal group,other groups were given disposable infusion of carcinogenic iodized oil via left lobe bronchus to induce lung cancer model.After modeling,those groups were given relevant medicine intravenously from Monday to Friday,while normal group and model group were given constant volume of normal saline intravenously for consecutive 16 weeks.The expression of multidrug resistance associated protein（MRP）,human multidrug resistance gene（MDR1）,P21 and P16 m RNA in lung tissue of rats were determined by RT-PCR;the expression of P53 protein in lung cancer tissue was determined by IHC method.The rate of positive expression was calculated,and pathological change of lung tissue was observed.RESULTS：Compared with normal group,the expression of MRP,MDR1,P21,P16 m RNA and P53 protein（positive rate of 66.67%）in lung tissue was increased significantly in model group（P〈0.05）;compared with model group,the expression of MRP,MDR1,P21,P16 m RNA and P53 protein（positive rate of 46.67%,46.67%,40.00%,13.33%） decreased in positive control group,TPG low-dose,medium-dose and high-dose groups in dose-dependent manner,and the decrease of TPG medium-dose and high-dose groups were more significant than that of positive control group（P〈0.05）;there was statistical significance in above indexes among TPG groups（P〈0.05）.CONCLUSIONS：TPG could inhibit the expression of MRP,MDR1,P21,P16 gene and P53 protein in lung cancer model rats significantly.