CAJ | 학술논문

目的探讨辛伐他汀对缺血再灌注后心肌无复流的影响及其潜在机制.方法雄性Wistar大鼠48只,随机分为假手术组、对照组及辛伐他汀组.对照组及辛伐他汀组结扎左冠状动脉建立大鼠心肌无复流模型,假手术组仅开胸不结扎冠状动脉.术后进行缺血范围(RA/LVA)、无复流范围(NA/RA)及梗死范围(MIA/RA)评估,测定心肌组织内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)活性,一氧化氮(NO)含量、髓过氧化物酶(MPO)活性及丙二醛(MDA)含量,并用免疫组织化学法测定心肌组织及微血管核因子(NF)-кB p65阳性指数.结果在缺血范围差异无统计学意义的条件下,辛伐他汀组无复流范围显著小于对照组(34.10±7.05比52.09±6.89,P<0.01),梗死范围也小于对照组(78.80±7.60比90.13±5.72,P<0.05).对照组及辛伐他汀组心肌组织iNOS活性、NO含量、MPO活性及MDA含量均高于假手术组,对照组eNOS活性显著低于假手术组(P均<0.05),辛伐他汀组eNOS活性与假手术组比较差异无统计学意义.辛伐他汀组心肌组织iNOS活性、NO含量、MPO活性及MDA含量均低于对照组(5.02±1.64比9.19±2.89,586.21±126.97比744.49±137.53,257.72±93.43比384.10±40.68,72.10±18.56比111.84±38.58,P均<0.05),eNOS活性显著高于对照组(7.08±1.74比3.72±0.98,P<0.01).对照组及辛伐他汀组左心室游离壁梗死周边心肌细胞及微动脉NF-кB p65阳性指数均显著高于假手术组,辛伐他汀组低于对照组(21.59±10.5比34.32±9.55,27.27±13.19比44.91±15.06,P均<0.05).结论辛伐他汀可以改善缺血再灌注后心肌无复流,其可能机制是通过改善内皮功能,抑制炎症反应,进而抑制中性粒细胞的激活浸润,减少活性氧簇的生成,最终减轻无复流.
목적 탐토신벌타정대결혈재관주후심기무복류적영향급기잠재궤제.방법 웅성Wistar대서48지,수궤분위가수술조、대조조급신벌타정조.대조조급신벌타정조결찰좌관상동맥건립대서심기무복류모형,가수술조부개흉불결찰관상동맥.술후진행결혈범위(RA/LVA)、무복류범위(NA/RA)급경사범위(MIA/RA)평고,측정심기조직내피형일양화담합매(eNOS)、유도형일양화담합매(iNOS)활성,일양화담(NO)함량、수과양화물매(MPO)활성급병이철(MDA)함량,병용면역조직화학법측정심기조직급미혈관핵인자(NF)-кB p65양성지수.결과 재결혈범위차이무통계학의의적조건하,신벌타정조무복류범위현저소우대조조(34.10±7.05비52.09±6.89,P<0.01),경사범위야소우대조조(78.80±7.60비90.13±5.72,P<0.05).대조조급신벌타정조심기조직iNOS활성、NO함량、MPO활성급MDA함량균고우가수술조,대조조eNOS활성현저저우가수술조(P균<0.05),신벌타정조eNOS활성여가수술조비교차이무통계학의의.신벌타정조심기조직iNOS활성、NO함량、MPO활성급MDA함량균저우대조조(5.02±1.64비9.19±2.89,586.21±126.97비744.49±137.53,257.72±93.43비384.10±40.68,72.10±18.56비111.84±38.58,P균<0.05),eNOS활성현저고우대조조(7.08±1.74비3.72±0.98,P<0.01).대조조급신벌타정조좌심실유리벽경사주변심기세포급미동맥NF-кB p65양성지수균현저고우가수술조,신벌타정조저우대조조(21.59±10.5비34.32±9.55,27.27±13.19비44.91±15.06,P균<0.05).결론 신벌타정가이개선결혈재관주후심기무복류,기가능궤제시통과개선내피공능,억제염증반응,진이억제중성립세포적격활침윤,감소활성양족적생성,최종감경무복류.
Objective The main objective of this study is to assess the the effect of simvastatin (sim) on myocardial no-reflow (NR) and explore the possible potential mechanisms. Methods Adult male Wistar rats were randomized into sham group (n = 12 ), L/R (90 min ischemia via coronary ligntion/120 min reperfusion, n = 18) and I/R plus sim group (20 mg · kg-1·d-1 sim pretreated via garage beginning 3 days before I/R, n = 18). After reperfusion, area at risk/area of left ventricular ( RA/LVA), area of NR, determined by the area not perfused by thioflavin-S/area at risk (NA/RA) and area of myocardial infarction/area at risk (MLA/RA) were measured. Myocardium homogenate was used to determine the activity of Enos,Inos and MPO, and the content of NO and MDA. Myocardial immunohistochemistry was performed to determine the positive index of NF-Кb p65 in cardiomyocytes and arteriole. Results The NR and myocardial infarction areas in I/R plus sim group were significantly smaller than those in I/R group (34. 10±7. 05 vs. 52. 09±6. 89, 78. 80±7. 60 vs. 90. 13±5.72, each P <0. 05) while the ischemia area was similar between the 2 groups (P 0. 05). The myocardial activities of Inos and MPO, the contents of NO and MDA were significantly lower while Enos activity was significantly higher in I/R plus sim group than those in I/R group (5. 02±1.64 vs. 9. 19±2. 89, 586. 21±126. 97 vs. 744. 49±137.53, 257.72± 93.43 vs. 384. 10±40. 68, 72. 10±18.56 vs. 111.84±38. 58, 7. 08±1.74 vs. 3.72±0. 98, all P < 0. 05). The positive index of NF-Кb p65 in cardiocytes and arteriole at left ventricular wall near the area of myocardial infarction was significantly lower in I/R plus sim group than that in I/R group (21.59±10. 5 vs. 34. 32±9. 55, 27.27±13.19 vs. 44. 91±15.06, each P < 0. 05). Conclusion Simvastatin could improve myocardial NR after ischemia-reperfusion by attenuating endothelial dysfunction and inhibiting inflammation and neutrophil activation.