CAJ | 학술논문

目的:评价猪急性心肌梗死(AMI)再灌注后氧化应激损伤在心肌无再流中的作用以及中药通心络的保护作用和机制.方法:中华小型猪30只,随机分成假手术组、模型组、小剂量(0.05 g·kg~(-1)·d~(-1))、中剂量(0.2 g·kg~(-1)·d~(-1))和大剂量(0.5 g·kg~(-1)·d~(-1))通心络治疗组,每组6只.冠状动脉阻断3 h,再灌注1 h建立AMI再灌注模型.测定并对比AMI前、后3 h和再灌注后1 h血清及再灌注后正常、再灌注和无再流区心肌组织中氧化应激指标总抗氧化能力(T-AOC)、总超氧化物歧化酶(T-SOD)、还原型谷胱甘肽(GSH)和丙二醛(MDA)含量的变化.结果:(1)与假手术组相比,模型组冠脉结扎3 h,血T-AOC、T-SOD和GSH含量均显著降低(均P<0.01),而MDA含量显著增加(P<0.01),再灌注后,上述指标降低和升高更显著(均P<0.01).(2)与假手术组和正常区心肌组织相比,模型组再灌注区心肌T-AOC、T-SOD和GSH含量均显著降低(均P<0.01),MDA含量则显著升高(P<0.01),而无再流区上述指标降低和升高比再灌注区更显著(均P<0.01).(3)与模型组相比,中剂量通心络能显著提高AMI 3 h血T-AOC、T-SOD含量,降低MDA含量(均P<0.05),并显著提高再灌注1 h血T-SOD含量(P<0.05);大剂量通心络能显著提高AMI 3 h和再灌注1 h血T-AOC、T-SOD含量,抑制MDA生成(均P<0.05).(4)中剂量通心络仅能显著提高再灌注区T-AOC含量(P<0.05),降低MDA含量(P<0.05);而大剂量则显著增加再灌注区T-AOC、T-SOD和GSH含量(均P<0.05),抑制MDA的合成(P<0.01),并显著增加无再流区T-AOC和T-SOD含量(均P<0.05),降低MDA的含量(P<0.01).结论:机体抗氧化防御功能降低和心肌局部氧化还原稳态失衡,可能是AMI再灌注后无再流发生的重要机制.中药通心络可能通过提高机体抗氧化防御能力,抑制心肌局部的氧化损伤,起到了减少无再流的作用.
목적:평개저급성심기경사(AMI)재관주후양화응격손상재심기무재류중적작용이급중약통심락적보호작용화궤제.방법:중화소형저30지,수궤분성가수술조、모형조、소제량(0.05 g·kg~(-1)·d~(-1))、중제량(0.2 g·kg~(-1)·d~(-1))화대제량(0.5 g·kg~(-1)·d~(-1))통심락치료조,매조6지.관상동맥조단3 h,재관주1 h건립AMI재관주모형.측정병대비AMI전、후3 h화재관주후1 h혈청급재관주후정상、재관주화무재류구심기조직중양화응격지표총항양화능력(T-AOC)、총초양화물기화매(T-SOD)、환원형곡광감태(GSH)화병이철(MDA)함량적변화.결과:(1)여가수술조상비,모형조관맥결찰3 h,혈T-AOC、T-SOD화GSH함량균현저강저(균P<0.01),이MDA함량현저증가(P<0.01),재관주후,상술지표강저화승고경현저(균P<0.01).(2)여가수술조화정상구심기조직상비,모형조재관주구심기T-AOC、T-SOD화GSH함량균현저강저(균P<0.01),MDA함량칙현저승고(P<0.01),이무재류구상술지표강저화승고비재관주구경현저(균P<0.01).(3)여모형조상비,중제량통심락능현저제고AMI 3 h혈T-AOC、T-SOD함량,강저MDA함량(균P<0.05),병현저제고재관주1 h혈T-SOD함량(P<0.05);대제량통심락능현저제고AMI 3 h화재관주1 h혈T-AOC、T-SOD함량,억제MDA생성(균P<0.05).(4)중제량통심락부능현저제고재관주구T-AOC함량(P<0.05),강저MDA함량(P<0.05);이대제량칙현저증가재관주구T-AOC、T-SOD화GSH함량(균P<0.05),억제MDA적합성(P<0.01),병현저증가무재류구T-AOC화T-SOD함량(균P<0.05),강저MDA적함량(P<0.01).결론:궤체항양화방어공능강저화심기국부양화환원은태실형,가능시AMI재관주후무재류발생적중요궤제.중약통심락가능통과제고궤체항양화방어능력,억제심기국부적양화손상,기도료감소무재류적작용.
AIM: To assess the degree of oxidative damage during acute myocardial infarction and reperfusion, and to clarify the protective effect of Tongxinluo in mini-swine model. METHODS: Thirty mini-swines were randomized into 5 study groups: sham group, model group, low dose (0.05 g·kg~(-1)·d~(-1)), medium dose (0.2 g·kg~(-1)·d~(-1)) and high dose (0.5 g·kg~(-1)·d~(-1)) of Tongxinluo groups (pretreated with Tongxinluo for 3 d). Animals except in sham group were subjected to 3 h of coronary occlusion followed by 1 h of reperfusion. Concentrations of total antioxidative capability (T-AOC), total superoxide dismutase (T-SOD), reduced glutathione (GSH) and malondialdehyde (MDA) in blood sample and the myocardium were measured. RESULTS: (1) T-AOC, T-SOD and GSH in serum significantly decreased (all P<0.05), while MDA significantly increased (P<0.01) at 3 h after AMI in comparison with those at baseline. Compared to those at 3 h after AMI, the contents of T-AOC, T-SOD and GSH at 1 h after reperfusion significantly decreased (all P<0.01), accompanied by increase of MDA (P<0.01). (2) Compared to those in normal area, levels of T-AOC, T-SOD and GSH in reperfusion myocardium decreased significantly (all P<0.01) and MDA increased significantly (P<0.01). T-AOC, T-SOD and GSH in no-reflow myocardium further decreased (all P<0.01) and MDA increased (P<0.01) as compared to those in reperfusion myocardium. (3) Compared to model group, medium dose of Tongxinluo increased the contents of T-AOC and T-SOD and reduced MDA production in serum at 3 h after AMI (all P<0.05), while medium dose of Tongxinluo increased T-SOD level at 1 h after reperfusion (P<0.05). High dose of Tongxinluo increased the levels of T-AOC and T-SOD and decreased MDA content in serum at 3 h after AMI and 1 h after reperfusion (all P<0.05). (4) The medium dose of Tongxinluo increased T-AOC content (P<0.05) and reduced MDA (P<0.05) in reperfusion myocardium, while high dose of Tongxinluo increased T-AOC, T-SOD and GSH (all P<0.05), reduced MDA (P<0.01) in reperfusion myocardium, and also increased T-AOC, T-SOD (all P<0.05), reduced MDA (P<0.01) in no-reflow area as compared to those in model group. CONCLUSION: Impairment of antioxidant defense system in vivo and imbalance of redox homeostasis in myocardium region might play an important role in the pathogenesis of no-reflow after myocardial acute infarction following reperfusion. Tongxinluo protects myocardium from reperfusion injury by improving antioxidant defense and attenuating oxidative damage.