机构地区:[1]西藏藏医药研究中心藏药活性成分及药理机制研究联合实验室,拉萨851414 [2]西藏民族大学教育部藏医学检测技术工程研究中心,咸阳712082
出 处:《中药药理与临床》2022年第4期107-112,共6页Pharmacology and Clinics of Chinese Materia Medica
基 金:国家自然科学基金资助项目(编号:81660722);西藏自治区自然科学基金项目(编号:XZ202101ZR0076G、2016ZR-MQ-07)。
摘 要:目的:研究麻花秦艽乙酸乙酯部位对大鼠心肌缺血/再灌注损伤(MIRI)的保护作用。方法:将40只SD雄性大鼠按体质量随机分为假手术对照组、模型对照组、普萘洛尔阳性对照(21 mg/kg)组、麻花秦艽1.67、6.66 g生药/kg组,各组灌胃相应药物或生理盐水,连续给药7 d。第8 d开始除假手术对照组外,其余组造模处理,大鼠进行左冠状动脉前降支结扎术以阻断大鼠心脏血流30 min,随后松开线结再灌注1 h,建立大鼠心肌缺血再灌注损伤模型。监测各组大鼠再灌注后心电图ST段抬高率;再灌注后处死大鼠,取心脏组织进行HE染色,观察组织病理变化;检测大鼠血清中乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)及超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)含量;通过RT-PCR技术检测大鼠心肌组织Bax、Bcl2、Caspase3基因表达;Western Blot检测大鼠心肌组织BAX、Bcl-2、Caspase3蛋白的表达。结果:与假手术对照组相比,模型对照组大鼠再灌注后Ⅱ导联ST段抬高率显著增加(P<0.01);大鼠心肌组织明显损伤;血清中LDH、CK-MB、MDA含量显著升高(P<0.01);SOD、GSH的活力明显降低(P<0.05或P<0.01);Caspase3 mRNA表达显著上调(P<0.01);Bcl2/Bax mRNA和蛋白比值降低,Bcl-2蛋白表达显著下调,BAX、Caspase3蛋白表达显著上调(P<0.01);与模型对照组相比,麻花秦艽药物各组大鼠再灌注后Ⅱ导联ST段抬高率显著降低(P<0.01);心肌组织损伤明显减轻;血清中LDH、CK-MB、MDA含量明显降低(P<0.05或P<0.01);SOD、GSH活力明显升高(P<0.05或P<0.01),Bcl-2/Bax mRNA和蛋白比值显著升高(P<0.01);Caspase3 mRNA表达显著下调(P<0.01);BCL-2的蛋白表达显著上调(P<0.01),BAX、Caspase3蛋白表达显著下调(P<0.01)。结论:麻花秦艽对心肌缺血再灌注大鼠具有明显地保护作用,其作用机制可能与抗凋亡相关。Objective: To investigate the protective effect of ethyl acetate extract of Gentiana straminea on myocardial ischemia/reperfusion injury(MIRI) in rats. Methods: Forty SD male rats were randomly divided into sham operation group, model control group, propranolol positive group(21 mg/kg), and G. straminea groups(1.67 and 6.66 g crude drug/kg). Rats in all groups were given corresponding drugs or normal saline water for 7 consecutive days. On day 8, except for sham operation group, the other rats were treated with ligation of the anterior descending branch of the left coronary artery to block the blood flow of the heart for 30 min, followed by reperfusion for 1 h after loosening the suture, to establish MIRI model. After modeling, the ST segment elevation of electrocardiogram after reperfusion in each group was monitored. The rats were sacrificed after reperfusion, and the heart tissue was taken for HE staining to observe the histopathological changes. The levels of lactate dehydrogenase(LDH), creatine kinase isoenzyme(CK MB), superoxide dismutase(SOD), malondialdehyde(MDA) and glutathione(GSH) in serum of rats were detected. The mRNA expressions of Bax, Bcl2 and Caspase3 in rat myocardium were detected by RT PCR. Western Blot was used to detect the protein expressions of Bax, Bcl2 and Caspase3 in rat myocardium. Results: Compared with the conditions in sham operation group, the lead II ST segment was increased after reperfusion in model control group(P<0.01);the myocardial tissue was damaged;the serum contents of LDH, CK MB and MDA were elevated(P<0.01);the activities of SOD and GSH were decreased(P<0.05 or P<0.01);the mRNA expressions of Bcl 2, Bax and Caspase3 and the protein expressions of Bax and Caspase3 were up regulated(P<0.01), while the protein expression of Bcl 2 was down regulated(P<0.01). Compared with the conditions in model control group, the lead II ST segment was reduced after reperfusion in all doses of G. straminea groups(P<0.01);the myocardial tissue injury was relieved;the serum contents of LDH,
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