目的 探讨柚皮素预处理对心肌缺血/再灌注损伤大鼠能量代谢的影响。方法 将大鼠随机分为5组(n=10):假手术组、模型组,柚皮素分为三个剂量组(100、50、25 mg/kg),于建立模型前7 d开始腹腔注射给药,通过结扎冠脉30 min再灌注2 h建立心肌缺血/再灌注损伤模型;再灌注结束后,采用比色法测定血清肌酸激酶(CK)和乳酸脱氢酶(LDH)活性,采用定磷法测定心肌组织Na+/K+-ATP酶和Ca2+/Mg2+-ATP酶的活力,采用染色法测定心肌梗死面积(myocardial infarction surface, MIS)。结果 柚皮素高剂量组MIS缩小至32.91%,与模型组MIS(39.78%)比较差异有统计学意义(P<0.05);柚皮素各剂量组CK活性分别降低为658.03、650.12、621.89 U/L,与模型组(809.45 U/L)比较,差异均有统计学意义(P<0.05或P<0.01);各剂量组LDH活性分别降低为1543.08、1506.27、1326.97 U/L,与模型组(2034.56 U/L)比较差异均有统计学意义(P<0.05或P< 0.01);柚皮素各剂量组可显著升高Na+/K+-ATP酶活力为6.82、6.83、6.94 mmol Pi/(g·h),与模型组[5.54 mmol Pi/(g·h)]比较差异均有统计学意义(P<0.05);高、中剂量组可显著升高,Ca2+/Mg2+-ATP酶活力为8.42、8.97 mmol Pi/(g·h),与模型组[7.06 mmol Pi/(g·h)]比较差异均有统计学意义(P<0.05)。结论 柚皮素预处理对心肌缺血/再灌注所致心肌损伤的保护作用可能与改善心肌组织的能量代谢有关。
Abstract
Objective To investigate the effect of naringenin on energy metabolism in rats with myocardial ischemia/reperfusion injury.Methods SD rats were divided randomly into sham group, model group, naringenin low dose group (25 mg/kg), naringenin medium dose group (50 mg/kg) and naringenin high dose group (100 mg/kg) (n=10). Naringenin was intraperitoneally injected once a day for 7 days before the modeling operation. A myocardial ischemia/reperfusion injury model was established by coronary artery ligation (30 min) and subsequent reperfusion (2 hours) in rats. After the modeling operation, the CK and LDH activities in sera were examined by chromatometry, Na+/K+-ATPase and Ca2+/Mg2+-ATPase activities in brain tissues were detected by phosphorus method and the myocardial infarction size (MIS) was determined by staining method.Results A high dose of naringenin significantly reduced MIS to 32.91% compared to 39.78% of model group (P<0.05). The CK activities in naringenin groups were 658.03, 650.12 and 621.89 U/L, respectively, which were significantly lower than 809.45 U/L of model group (P<0.05 or P<0.01). Naringenin significantly reduced LDH activities to 1543.08, 1506.27 and 1326.97 U/L, respectively, compared to 2034.56 U/L of model group (P<0.05 or P<0.01). Naringenin evidently increased Na+/K+-ATPase activities to 6.82, 6.83 and 6.94 mmol Pi/(g·h), respectively, compared to 5.54 mmol Pi/(g·h) of model group (P<0.05). Naringenin (100 and 50 mg/kg) significantly increased Ca2+/Mg2+-ATPase activities to 8.42 and 8.97 mmol Pi/(g·h), respectively, compared to 7.06 mmol Pi/(g·h) of model group (P<0.05).Conclusions The protective effects of naringenin pretreatment in myocardial ischemia/reperfusion injury seems to be associated with the improvement of energy metabolism.
关键词
柚皮素 /
心肌缺血/再灌注损伤 /
大鼠 /
能量代谢
Key words
naringenin /
myocardial ischemia/reperfusion injury /
rat /
energy metabolism
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参考文献
[1] Alam M A, Subhan N, Rahman M M, et al. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action [J]. Adv Nutr, 2014, 5(4): 404-417.
[2] Rani N, Bharti S, Krishnamurthy B, et al. Pharmacological properties and therapeutic potential of naringenin: a citrus flavonoid of pharmaceutical promise [J]. Curr Pharm Des, 2016, 22(28): 4341-4359..
[3] Testai L, Martelli A, Marino A, et al. The activation of mitochondrial BK potassium channels contributes to the protective effects of naringenin against myocardial ischemia/reperfusion injury [J]. Biochem Pharmacol, 2013, 85(11): 1634-1643.
[4] 许爱斌,王 飞,李俊峡,等.柚皮素预处理对大鼠心肌缺血再灌注损伤的保护作用[J].中国循证心血管医学杂志,2013,5(4):416-418.
[5] 梅繁勃,王文妍,李冬梅,等.柚皮素对缺血再灌注损伤心肌保护作用的机制研究[J].实用药物与临床,2016,19(5):541-544.
[6] 刘新义,李健和,向大雄,等.聚乙二醇化葛根素对大鼠心肌缺血再灌注损伤的保护作用[J].中草药,2013,44(3):327-330.
[7] 杨建业,张迎春,唐俊明,等.大鼠心肌缺血再灌注后心功能变化与心肌梗死面积的相关性分析[J].实验动物与比较医学,2008,28(1):4-9.
[8] 张宝红.药物预处理与缺血预处理对心肌缺血再灌注损伤保护作用的实验研究[D].太原:山西医科大学,2003.
[9] Nakai K, Nakai K, Suwabe A. Biochemical marker for myocardial injury [J]. Rinsho Byori, 2002, 50(12): 1140-1145.
[10] Qin H, Walcott G P, Killingsworth C R, et al. Impact of myocardial ischemia and reperfusion on ventricular defibrillation patterns, energy requirements, and detection of recovery [J]. Circulation, 2002,105(21):2537-2542.
[11] Inserte J, Garcia-Dorado D, Hernando V, et al. Calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion contributes to cell death after myocardial ischemia [J]. Circ Res, 2005,97(5):465-473.
[12] 程永生,陈 宇,李 冬.钙超载及其在心肌缺血/再灌注损伤中的作用机制研究现状[J].中国医学创新,2013,10(3):150-151.