Zhang Da-wu, Zhang Lei, Liu Jian-gang, Wang Cheng-long, Shi Da-zhuo, Chen Ke-ji
Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Zhong Xi Yi Jie He Xue Bao. 2010 May;8(5):465-71.
To observe the effects of Chinese patent medicines with the function of replenishing qi to activate blood (RQAB) plus ischemic postconditioning (IPoC) in protecting myocardium of rats from ischemia-reperfusion (I/R) injury, and to explore the possible mechanisms.
Seventy-five Sprague-Dawley rats were randomly divided into sham-operated group (the suture was penetrated around the left anterior descending coronary artery, but not tied, n=15), I/R group (30 minutes of in situ transient occlusion of the left anterior descending artery, followed by 1 hour of reperfusion, n=15), IPoC group (30 minutes occlusion of the left anterior descending artery, followed by 3 cycles of 10 s of reperfusion/10 s of ischemia before 1-hour reperfusion, n=15), RQAB plus IPoC group (pretreated with 0.162 g/kg Xinyue Capsule and 0.135 g/kg Xiongshao Capsule for 14 days, and treated with IPoC 2 h after the final gavage, n=15), fosinopril sodium plus IPoC group (pretreated with fosinopril sodium, 0.9 mg/kg, n=15). Serum creatine kinase-MB (CK-MB) activity and cardiac troponin T (cTnT) level were detected; myocardial infarction size was measured by nitrotetrazolium blue chloride staining; Toll-like receptor 2 (TLR2) and TLR4 in myocardial tissue were examined by immunohistochemical method; interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) levels in myocardial tissue were examined by enzyme-linked immunosorbant assay.
Compared with the I/R group, myocardial enzymes and infarction size were decreased significantly in the IPoC group (P<0.01); expressions of TLR2 and TLR4 and levels of IL-1beta and IL-6 in myocardial tissues were also significantly lower than those in the I/R group (P<0.05). Compared with the fosinopril sodium plus IPoC group, expressions of TLR2 and TLR4 were decreased significantly in the RQAB plus IPoC group (P<0.05, P<0.01). Compared with IPoC, RQAB plus IPoC reduced the infarction size and the release of myocardial enzyme CK-MB (P<0.01), and decreased the expressions of TLR2 and TLR4 and the levels of IL-1beta and IL-6 (P<0.05, P<0.01) in myocardial tissues.
Pretreatment with Chinese herbs for nourishing qi and activating blood circulation can enhance the protective effect of IPoC on rat myocardial I/R injury, and its mechanism may be related to inhibition of TLR expression and expressions of the downstream proinflammatory cytokines.
观察益气活血类中成药联合缺血后处理（IPoC）对大鼠心肌缺血再灌注（I/R）损伤的保护作用，并探讨其可能机制。
将75只Sprague-Dawley大鼠随机分为假手术组（在左冠状动脉前降支周围穿线，但不结扎，n=15）、I/R组（左前降支原位短暂阻断30分钟，随后再灌注1小时，n=15）、IPoC组（左前降支阻断30分钟，在1小时再灌注前进行3个循环的10秒再灌注/10秒缺血，n=15）、益气活血联合IPoC组（用0.162 g/kg心悦胶囊和0.135 g/kg芎芍胶囊预处理14天，末次灌胃后2小时进行IPoC处理，n=15）、福辛普利钠联合IPoC组（用0.9 mg/kg福辛普利钠预处理，n=15）。检测血清肌酸激酶同工酶（CK-MB）活性和心肌肌钙蛋白T（cTnT）水平；用氯化硝基四氮唑蓝染色法测定心肌梗死面积；采用免疫组织化学方法检测心肌组织中Toll样受体2（TLR2）和TLR4；采用酶联免疫吸附测定法检测心肌组织中白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）水平。
与I/R组比较，IPoC组心肌酶和梗死面积明显降低（P<0.01）；心肌组织中TLR2和TLR4表达以及IL-1β和IL-6水平也明显低于I/R组（P<0.05）。与福辛普利钠联合IPoC组比较，益气活血联合IPoC组TLR2和TLR4表达明显降低（P<0.05，P<0.01）。与IPoC组比较，益气活血联合IPoC组梗死面积和心肌酶CK-MB释放减少（P<0.01），心肌组织中TLR2和TLR4表达以及IL-1β和IL-6水平降低（P<0.05，P<0.01）。
益气活血类中药预处理可增强IPoC对大鼠心肌I/R损伤的保护作用，其机制可能与抑制TLR表达及下游促炎细胞因子表达有关。
