活血解毒中药配伍对大鼠缺血后适应心肌组织的保护作用

Protective effect of Chinese herbs for activating blood circulation and detoxification （活血解素养） combined with ischemic postconditioning on rats

目的观察活血中药川芎、当归和解毒中药黄连有效组分配伍后处理联合缺血后适应（IPOC）干预对大鼠心肌缺血／再灌注（I／R）损伤后炎症因子和氧化应激的作用。方法将75只SD大鼠按随机数字表法分为5组，每组15只。①假手术组：左冠状动脉（冠脉）前降支下穿线不结扎；②I／R组：结扎左冠脉前降支致心肌缺血30min后，再灌注1h；③IPOC组：结扎左冠脉前降支30min后，给予短暂再灌注10s，再次缺血10s，重复3次后持续再灌注1h；④西药对照组：连续灌胃福辛普利钠（O．9mg／kg）14d后行IPOC；⑤活血解毒组：连续灌胃中药复方川芎胶囊（有效成分川芎嗪3．20mg／g、阿魏酸1．73mg／g）0．40g／kg和黄连生物碱（O．16g／kg）2ml，14d后行IPOC。假手术、I／R、IPOC组连续14d灌胃等量蒸馏水。实验结束后腹主动脉取血，检测血清肌酸激酶同工酶（CK—MB）、肌钙蛋白T（cTnT）、超氧化物歧化酶（SOD）、丙二醛（MDA）、白细胞介素（IL-1β、IL-6）、高敏C-反应蛋白（hs—CRP）水平；取心肌组织，光镜下观察其形态结构，并计算大鼠左室梗死率。结果与I／R组比较，IPOC组大鼠血清CK—MB活性和cTnT含量显著降低，左室梗死率显著下降，氧化应激指标明显改善，血清炎症因子IL-1β、IL-6和hs—CRP含量均显著降低（P〈0．05或P〈0．01）。活血解毒中药预处理与IPOC联合作用可进一步降低大鼠左室梗死率和CK—MB活性，并可升高血清SOD水平，降低IL-6水平（P〈0．05或P〈0．01）。结论活血解毒中药配伍联合IPOC可显著减轻I／R所造成的炎症反应及氧化应激，抑制心肌酶的释放，减小动物心肌梗死面积，保护心肌组织。

Objective To investigate the protective effect of Chinese herbs （rhzoma chuanxiong （川芎）, radix angelicae sinensis （当当）, rhizoma coptidis （黄连）] for activating blood circulation and detoxification （活血解素养, ABCD） associated with ischemic postconditioning （IPOC） on inflammatory factors and oxidative stress after myocardial ischemia/reperfusion （I/R） injury in rats. Methods Seventy-five Sprague-Dawley （SD） rats were randomly divided into five groups （each, n= 15）： （1）sham-operated group： a suture was penetrated around the left anterior descending coronary （LAD）, hut not tied; （2）I/R group： ligation of the LAD leading to ischemia for 30 minutes followed by 1 hour reperfusion; （3）IPOC group： occlusion of the LAD for 30 minutes, followed by repetitive three times of alternate reperfusion 10 s and ischemia 10 s, and lasted 1 hour of reperfusion; （4）western medicine control group., pretreated with intragastrical administration of fosinopril sodium for 14 days, 0.9 mg/kg, then treated with IPOC 2 hours after the final gavage; （5）ABCD group： pretreated with intragastrical administration of 0. 40 g/kg Fufang Chuanxiong capsule （复方川芎胶囊） which was composed of two constituents., ligustrazine （3.20 mg/g） and ferulic acid （1.73 mg/g）, combined with 2 ml rhizoma coptidis alkaloids （黄连生物碱, 0.16 g/kg） for 14 days, then treated with IPOC 2 hours after the final garage. Sham-operated, I/R and IPOC groups were given intragastric administration with equivalent distilled water for 14 days. After 60 minutes of reperfusion, blood was drawn from abdominal aorta and serum was separated, and the rat heart was taken. The serum levels of MB isoenzyme of ereatine kinase （CK-MB）, cardiac troponin T （cTnT）, superoxide dismutase （SOD）, malondialdehyde （MDA）, interleukin （IL -1β, IL-6） and high sensitive-C reactive protein （hs-CRP） were detected. Under light microscope, the myocardial structures were observed, and the rate of myocardial infarct in the left ventricle was calculated. Results Compared with the I/R group, the serum CK-MB activity and cTnT levels decreased significantly, myocardial infarct rate reduced remarkably, index of oxidative stress improved and the levels of serum inflammatory cytokines IL-1β, IL-6 and hs-CRP decreased obviously in IPOC group （P〈0.05 or P〈0.01）. Compared with I/R group, the myocardial infarct rate and CK-MB activity were further decreased significantly in ABCD group, the serum level of SOD increased remarkably, the serum level of IL-6 decreased obviously in ABCD group （P〈0.05 or P〈0.01）. Conclusion The combination of Chinese herbs for ABCD and IPOC can play an important role in the protection of myocardial tissues and reduction of the size of myocardial infarct by alleviating the inflammatory reaction and oxidative stress induced by I/R injury and inhibiting the release of myocardial enzymes.