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大鼠预先灌胃福辛普利钠,观察其和缺血后适应(ischemic postconditioning,IPoC)对大鼠心肌缺血再灌注(ischemic reperfusion,I/R)损伤后心肌组织Toll样受体(toll-like receptor,TLR)表达及心肌组织炎症浸润的影响.将60只SD(Spragu-Dawley)大鼠随机分为假手术组、I/R组、IPoC组以及福辛普利钠+IPoC组,每组15只.假手术组大鼠心脏前降支下置线不结扎;I/R组予以心脏前降支结扎30min,再灌注1h;IPoC组给予心脏前降支结扎30min,后予以3次10s的再灌注/缺血循环,再持续灌注1h;福辛普利钠+IPoC组则预先给予福辛普利钠片0.9mg/kg,连续灌胃14d,于末次灌胃2h后,施以IPoC组的干预过程.所有实验大鼠腹主动脉取血并分离出心脏组织.比色法测定血清肌钙蛋白T(cardiac troponinT,cTNT)的含量,NBT染色测定大鼠左室心肌梗死面积,酶联免疫吸附测定法测定心肌组织单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平.免疫组织化学方法测定心肌组织TLR2及TLR4的表达,HE染色观察心肌组织炎性细胞的浸润.结果表明,与I/R组比较,IPoC组大鼠心肌梗死面积明显缩小(P<0.01),大鼠血清cTNT水平显著降低(P<0.01),心肌组织MCP-1,TNF-α含量和炎性细胞浸润数量明显下降(P<0.05,P<0.01),心肌组织TLR2及TLR4的表达被显著抑制(P<0.01);与IPoC组比较,福辛普利钠预处理可进一步降低IPoC大鼠心肌梗死面积(P<0.05),心肌组织TNF-α水平也显著降低(P<0.01),对心肌TLR2及TLR4的表达有进一步抑制(P<0.05).血管紧张素转化酶抑制剂福辛普利钠预处理可加强IPoC对I/R大鼠心肌的保护作用,其机理可能与抑制TLR介导的炎症信号通路和趋化因子反应有关.
Rats were pre-treated with fosinopril sodium, and the effect of IPoC on toll-like receptors (Toll-like receptors) in myocardial tissue after myocardial ischemia / reperfusion (I / R) injury was observed. like receptor (TLR) and inflammatory infiltration in myocardial tissue.All 60 Sprague-Dawley rats were randomly divided into sham operation group, I / R group, IPoC group and fosinopril sodium + IPoC group, Each group of 15. Rats in sham operation group were not ligated under the anterior descending branches of the heart, while the anterior descending branch was ligated for 30 minutes and reperfused for 1 hour in the I / R group. The anterior descending branch of the IPoC group was ligated for 30 minutes, 10s of reperfusion / ischemia circulation, and then continued to perfusion 1h; Fosinopril sodium + IPoC group was pre-given fosinopril sodium tablets 0.9mg / kg, continuous gavage 14d, 2h after the last gavage, IPoC group.All the experimental rats were sacrificed and blood was taken from the abdominal aorta to separate the cardiac tissue.The content of serum cardiac troponin T (cTNT) was measured by colorimetry, the area of left ventricular myocardial infarction was determined by NBT staining, The levels of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis were determined by enzyme-linked immunosorbent assay (TNF-α) were detected by immunohistochemical method.The expressions of TLR2 and TLR4 in myocardium were detected by immunohistochemical method.The infiltration of inflammatory cells in myocardium was observed by HE staining.The results showed that compared with I / R group, The area of myocardial infarction in IPoC group was significantly reduced (P <0.01), the level of cTNT in serum was significantly decreased (P <0.01), the content of MCP-1 and TNF-α in myocardial tissue and the number of inflammatory cells were significantly decreased , P <0.01). The expression of TLR2 and TLR4 in myocardium was significantly inhibited (P <0.01). Compared with IPoC group, preconditioning with fosinopril could further reduce the area of myocardial infarction (P <0.05) (P <0.01), and further inhibited the expression of TLR2 and TLR4 in myocardium (P <0.05) .The pretreatment with angiotensin converting enzyme inhibitor fosinopril could enhance the effect of IPoC on I / R cardiomyocytes, its mechanism may be related to the inhibition of TLR-mediated inflammatory signaling pathway and chemokine response.