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目的:在参心麦和颗粒治疗缺血再灌注损伤大鼠模型疗效的基础上,探讨参心麦和颗粒对心肌缺血损伤大鼠在核转录因子-κB(NF-κB)信号通路中的调控作用。方法:SD大鼠60只大鼠,随机分成假手术组、模型组、地尔硫卓组(36 mg·kg-1)、参心麦和颗粒低、中、高剂量(0.17,0.51,1.53 g·kg-1)组,除假手术组外,其余各组造成缺血再灌注损伤模型,造模成功后,各给药组连续ig给予相应药物7 d,每天1次;基于NF-κB信号通路,采用ELISA检测大鼠血清白细胞介素-6(IL-6)和IL-8水平;采用RT-PCR法检测大鼠心肌组织NF-κB,肿瘤坏死因子-α(TNF-α),诱生型一氧化氮合成酶(i NOS),细胞间黏附分子(ICAM-1)和血管细胞黏附分子(VCAM-1)mRNA表达水平;采用Western blotting法检测大鼠心肌组织血管内皮生长因子(VEGF),热休克蛋白(HSP 70)和环氧化酶-2(COX-2)蛋白表达水平。结果:与假手术组比较,模型组IL-6和IL-8含量明显升高(P<0.01),NF-κB,TNF-α,i NOS,ICAM-1和VCAM-1 mRNA表达明显升高(P<0.01),COX-2蛋白表达明显升高(P<0.01),VEGF和HSP 70蛋白表达明显降低(P<0.01);与模型组比较,参心麦和颗粒能显著降低NF-κB信号通路中IL-6和IL-8含量(P<0.01),抑制NF-κB,TNF-α,i NOS,ICAM-1和VCAM-1 mRNA的表达(P<0.01),抑制COX-2蛋白表达(P<0.01),促进VEGF和HSP 70蛋白表达(P<0.01)。结论:参心麦和颗粒具有明显的抗心肌缺血损伤作用,其机制是通过抑制NF-κB信号通路中的炎症因子,激活血管保护因子,二者协同作用实现的,该研究为参心麦和颗粒治疗冠心病的临床推广应用提供理论依据。
OBJECTIVE: To investigate the effect of Shenxin Maihe Granule on nuclear factor-κB (NF-κB) signaling pathway in rats with myocardial ischemic injury based on the therapeutic effect of Shenhe Maihe Granule on rat model of ischemia-reperfusion injury. Regulation. Methods: Sixty SD rats were randomly divided into sham operation group, model group, diltiazem group (36 mg · kg -1), Shenmai Maihe granule at low, medium and high doses (0.17,0.51,1.53 g · kg -1) -1) group, except the sham operation group, the rest of the groups caused the model of ischemia-reperfusion injury. After the model was established successfully, each administration group was administered ig with the corresponding drugs for 7 days once a day. Based on the NF-κB signaling pathway, Serum levels of IL-6 and IL-8 were detected by ELISA. The expressions of NF-κB, TNF-α, The expressions of iNOS, ICAM-1 and VCAM-1 mRNA in myocardium were detected by Western blotting. The expressions of vascular endothelial growth factor (VEGF), nitric oxide synthase Heat shock protein (HSP70) and cyclooxygenase-2 (COX-2) protein expression levels. Results: The levels of IL-6 and IL-8 in the model group were significantly increased (P <0.01), and the expressions of NF-κB, TNF-α, iNOS, ICAM-1 and VCAM- (P <0.01), the expression of COX-2 protein was significantly increased (P <0.01), while the expression of VEGF and HSP70 protein was significantly decreased (P <0.01). Compared with the model group, Shenxin Maihe Granule could significantly decrease the expression of NF- (P <0.01), inhibit the expression of NF-κB, TNF-α, iNOS, ICAM-1 and VCAM-1 mRNA and the expression of COX-2 protein (P <0.01), and promoted the expression of VEGF and HSP70 (P <0.01). Conclusion: Shenxin Maihe Granule has obvious anti-ischemic effect. Its mechanism is through the inhibition of inflammatory factors in NF-κB signaling pathway and activation of vascular protective factor, And particle treatment of coronary heart disease to promote clinical application of theoretical basis.