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目的:观察参芍胶囊及有效组分对大鼠心肌缺血再灌注损伤(MIRI)的保护作用及基于核转录因子-κB(NF-κB)炎症通路探讨其作用机制。方法:雄性Wistar大鼠,采用左冠状动脉前降支结扎30 min,再灌注120 min制备大鼠MIRI模型。随机分为7组,分别为假手术组(Sham),模型组(I/R),参芍胶囊250 mg·kg~(-1)组(SS250),参芍胶囊500 mg·kg~(-1)组(SS500),人参茎叶总皂苷组(TGSL),白芍浸膏粉组(Pae)及阿托伐他汀组(Ator),预灌胃7 d。2,3,5-氯化三苯基四氮唑(TTC)法测大鼠心肌梗死面积;生化法测血清肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH);酶联免疫吸附测定(ELISA)法测白细胞介素(IL)-1β,肿瘤坏死因子-α(TNF-α)和IL-10含量;蛋白质免疫印迹(Western blot)测NF-κBp65,p-NF-κBp65水平。结果:与I/R组比较,SS250组,SS500组,TGSL组,Pae组及Ator组心肌梗死面积缩小(P<0.05,P<0.01);SS250组,SS500组,TGSL组及Ator组血清CKMB及LDH水平明显下降(P<0.05,P<0.01);SS250组,SS500组和TGSL组TNF-α含量降低(P<0.05,P<0.01);SS250组,SS500组,Pae组和Ator组IL-1β含量明显降低(P<0.05);SS250组,SS500组IL-10含量明显升高(P<0.05,P<0.01);SS250组和SS500组p-NF-κBp65蛋白表达水平显著降低(P<0.01)。结论:参芍胶囊对MIRI大鼠心脏具有保护作用,抑制NF-κB炎症通路的过度激活是其作用机制之一,在抑制NF-κB表达方面参芍胶囊高剂量组优于其单一有效成分。
Objective: To observe the protective effect of Shen-shao capsule and its effective components on myocardial ischemia-reperfusion injury (MIRI) in rats and its mechanism of action based on the nuclear factor-κB (NF-κB) pathway. Methods: Male Wistar rats were used to establish MIRI model by ligating the left anterior descending coronary artery for 30 min and reperfusion for 120 min. The rats were randomly divided into 7 groups: sham group, model group (I / R), Shen Sha capsule 250 mg · kg -1 (SS250), Shen Sha capsule 500 mg · kg -1 1) group (SS500), ginseng stem and leaves total saponin group (TGSL), Pae and paeonol group (Ator), pre-gavage for 7 days. The area of myocardial infarction was measured by TTC method with 2,3,5-chlorotoluene chloride (TTC) method. Serum creatine kinase (CK-MB) and lactate dehydrogenase (LDH) The contents of IL-1β, TNF-α and IL-10 were measured by ELISA. The expressions of NF-κB p65 and p-NF- κBp65 levels. Results: Compared with I / R group, the area of myocardial infarction in SS250 group, SS500 group, TGSL group, Pae group and Ator group was reduced (P <0.05, P <0.01); in SS250 group, SS500 group, TGSL group and Ator group, (P <0.05, P <0.01). The levels of TNF-α in SS250 group, SS500 group and TGSL group were significantly lower than those in SS250 group, SS500 group, Pae group and Ator group (P <0.05, P <0.01). The expression of p-NF-κBp65 protein in SS250 group and SS500 group was significantly lower than that in SS250 group and SS500 group (P <0.05, P < <0.01). Conclusion: Shen-Shao Capsule has a protective effect on the heart of MIRI rats and inhibits the over-activation of NF-κB inflammatory pathway. It is one of the mechanisms of action. Shen-ge capsule high-dose group is superior to single active ingredient in inhibiting NF-κB expression.