机构地区:[1]承德医学院,河北承德067000
出 处:《中国实验方剂学杂志》2017年第12期132-137,共6页Chinese Journal of Experimental Traditional Medical Formulae
基 金:河北省自然科学基金项目(C2011406009);河北省教育厅重点项目(ZD20131068)
摘 要:目的:通过检测丹皮酚联合三七总皂苷用药后大鼠心肌中肿瘤坏死因子-α(TNF-α),白细胞介素-1β(IL-1β)的mRNA的变化,探讨丹皮酚联合三七总皂苷对大鼠急性心肌梗死(AMI)后引发心室重构的影响及机制。方法:80只雄性SD大鼠中随机选取的70只,结扎左冠状动脉的前降支制备AMI大鼠的动物模型。存活且成模大鼠依照干预不同随机的分成模型组、丹皮酚(Pae 8 mg·kg^(-1))组、三七总皂苷(NTS 40 mg·kg^(-1))组、联合低剂量组(Pae 4 mg·kg^(-1)+NTS 20 mg·kg^(-1))、联合高剂量组(Pae 8 mg·kg^(-1)+NTS 40 mg·kg^(-1)),卡托普利组(10 mg·kg^(-1))阳性药组,此外设立假手术组。各组分别给予相应药物腹腔注射,连续28 d。苏木素-伊红(HE)染色法观察各组大鼠心肌组织的病理学变化,蛋白质免疫印迹(Western blot)法检测NF-κBp65,p-IκB-α蛋白的表达水平,逆转录PCR(RT-PCR)检测TNF-α和IL-1βmRNA表达水平。结果:与假手术组比较,模型组心肌病理改变明显,NF-κBp65,p-IκB-α蛋白的表达和TNF-α,IL-1β的mRNA表达显著升高(P<0.01);同模型组比较,各用药组心肌病理改变有不同程度改善,目的蛋白与目的基因的表达显著降低(P<0.01);并且联合用药组中各指标的改善情况明显优于单味药组(P<0.05,P<0.01),联合用药高剂量组较低剂量组作用更显著(P<0.05,P<0.01)。结论:丹皮酚联合三七总皂苷能协同改善心梗后大鼠心室重构,其机制可能与阻断NF-κB/IκB信号通路,下调TNF-α和IL-1βmRNA的表达减少炎症反应有关。Objective: To investigate the effect and mechanism of paeonol (Pae) combined with Notoginseng total saponins (NTS) on tumor necrosis factor tumor necrosis factor-α (TNF-α) and interleukin interleukin-1β (IL-1β) mRNA expression levels in myocardium tissues in rats with ventricular remodeling after acute myocardial infarction (AMI). Method: Totally 80 male SD rats were selected, and 70 of them were randomly used to establish AMI rat models by ligaturing left anterior descending (LAD) artery. Alive and successfully modeled rats were randomly divided into model group, Pae group (8 mg·kg^-1) , NTS group (40mg·kg^-1), Pae + NTS group low-dose group (Pae 4 mg·kg^-1+ NTS 20mg·kg^-1), high-dose group (Pae 8mg·kg^-1 + NTS 40mg·kg^-1) and captopril positive control group (10 mg·kg^-1) according to different interventions, and another 10 rats were used as sham operation group. The rats in various treatment groups received intraperitoneal injection of drugs for 28 days. Then the pathology changes of myocardial tissues were observed by htoxylin eosin (HE) staining; the protein expression levels of NF-κBp65 and p-IκB-α were detected by Western blot assay, and the mRNA expression levels of TNF-α and IL-1β were detected by reverse transcriptase PCR ( RT- PCR). Result: As compared with sham operation group, there were obvious myocardial pathological changes in model group, with significantly increased NF-κBp65 and p-IκB-α protein expression levels as well as TNF-α and IL-1β mRNA expression levels (P 〈 0.01 ). As compared with the model group, the myocardial pathological changes were improved to varying degrees in various treatment groups, with significantly decreased expressions of interest protein and interest mRNA (P 〈 0. 01 ). In addition, the improvement in combined drug use groups was superior to that in single substance drug group (P 〈 0. 05, P 〈 0. 01 ), and the effect in high dose combined drug use group was more signif
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