CAJ | 학술논문

目的研究曲美他嗪对大鼠急性心肌缺血再灌注损伤的影响.方法实验大鼠40只,按随机数字表法抽取30只分为再灌注损伤模型组(MIRI)(n=10)、曲美他嗪低剂量组(n=l0)、曲美他嗪高剂量组(n=10),余10只为假手术组.制作再灌注损伤模型后,观察各组大鼠血流动力学变化,测定肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平和观察光镜、电镜下心肌组织切片.结果 (1)各组大鼠血流动力学指标比较:与假手术组[左心室收缩压(LVSP)(198±35.5)mmHg,左心室舒张末压(LVEDP) (17 ±9.18) mmHg,左心室内压最大上升速率(+dp/dtmax)(11050±1517.4) mmHg/s,左心室内压最大下降速率(-dp/dtmax)(9175±1900) mmHg/s]比较,模型组[LVSP(143±24.5)mmHg,LVEDP(37.5±7.16) mmHg,+dp/dtmax(7450±1755.1) mmHg/s,-dp/dtmax(6075±1641) Hg/S]、曲美他嗪低剂量组[LVSP(154.5±31.1) mmHg,LVEDP(31.3±12.6)mmHg,+dp/dtmax(8527.7±2251.5) mmHg/s,-dp/dtmax(6694±2242.2)mmHg/s]、曲美他嗪高剂量组[LVSP(168.3±17.6) mmHg,LVEDP(28±10.05) mmHg,+ dp/dtmax (9213.6±1747) mmHg/s,-dp/dtmax(7568±1462.4) mmHg/s]大鼠的LVEDP明显升高,LVSP、+dp/dtmax、-dp/dtmax明显减少;与模型组相比,曲美他嗪高剂量组LVEDP明显减低,+dp/dtmax、-dp/dtmax明显增加,差异具有统计学意义(P＜0.01).(2)各组大鼠氧化应激损伤的比较:与假手术组[IL-6(2556.5±662.9)ng/ml,TNF-α(134±73.7) ng/ml]比较,模型组[IL-6(3664.0±995.7) ng/ml,TNF-α(443 ±22.1)ng/ml]、曲美他嗪低剂量组[IL-6(3692.8±1545.2) ng/ml,TNF-α(295±24.2)ng/ml]、曲美他嗪高剂量组[IL-6 (2654.8±681.7) ng/ml,TNF-α(230 ±7.8)ng/ml]大鼠TNF-α、IL-6水平明显增高;与模型组相比,曲美他嗪高剂量组TNF-α、IL-6水平明显减低,差异具有统计学意义(P＜0.01).(3)光镜及电镜下观察:除假手术组大鼠外各组大鼠均有不同程度损伤,曲美他嗪高剂量组损伤较轻.结论曲美他嗪高剂量对大鼠心肌缺血再灌注损伤有保护作用. 目的研究麯美他嗪對大鼠急性心肌缺血再灌註損傷的影響.方法實驗大鼠40隻,按隨機數字錶法抽取30隻分為再灌註損傷模型組(MIRI)(n=10)、麯美他嗪低劑量組(n=l0)、麯美他嗪高劑量組(n=10),餘10隻為假手術組.製作再灌註損傷模型後,觀察各組大鼠血流動力學變化,測定腫瘤壞死因子-α(TNF-α)、白細胞介素-6(IL-6)水平和觀察光鏡、電鏡下心肌組織切片.結果 (1)各組大鼠血流動力學指標比較:與假手術組[左心室收縮壓(LVSP)(198±35.5)mmHg,左心室舒張末壓(LVEDP) (17 ±9.18) mmHg,左心室內壓最大上升速率(+dp/dtmax)(11050±1517.4) mmHg/s,左心室內壓最大下降速率(-dp/dtmax)(9175±1900) mmHg/s]比較,模型組[LVSP(143±24.5)mmHg,LVEDP(37.5±7.16) mmHg,+dp/dtmax(7450±1755.1) mmHg/s,-dp/dtmax(6075±1641) Hg/S]、麯美他嗪低劑量組[LVSP(154.5±31.1) mmHg,LVEDP(31.3±12.6)mmHg,+dp/dtmax(8527.7±2251.5) mmHg/s,-dp/dtmax(6694±2242.2)mmHg/s]、麯美他嗪高劑量組[LVSP(168.3±17.6) mmHg,LVEDP(28±10.05) mmHg,+ dp/dtmax (9213.6±1747) mmHg/s,-dp/dtmax(7568±1462.4) mmHg/s]大鼠的LVEDP明顯升高,LVSP、+dp/dtmax、-dp/dtmax明顯減少;與模型組相比,麯美他嗪高劑量組LVEDP明顯減低,+dp/dtmax、-dp/dtmax明顯增加,差異具有統計學意義(P＜0.01).(2)各組大鼠氧化應激損傷的比較:與假手術組[IL-6(2556.5±662.9)ng/ml,TNF-α(134±73.7) ng/ml]比較,模型組[IL-6(3664.0±995.7) ng/ml,TNF-α(443 ±22.1)ng/ml]、麯美他嗪低劑量組[IL-6(3692.8±1545.2) ng/ml,TNF-α(295±24.2)ng/ml]、麯美他嗪高劑量組[IL-6 (2654.8±681.7) ng/ml,TNF-α(230 ±7.8)ng/ml]大鼠TNF-α、IL-6水平明顯增高;與模型組相比,麯美他嗪高劑量組TNF-α、IL-6水平明顯減低,差異具有統計學意義(P＜0.01).(3)光鏡及電鏡下觀察:除假手術組大鼠外各組大鼠均有不同程度損傷,麯美他嗪高劑量組損傷較輕.結論麯美他嗪高劑量對大鼠心肌缺血再灌註損傷有保護作用.
목적 연구곡미타진대대서급성심기결혈재관주손상적영향.방법 실험대서40지,안수궤수자표법추취30지분위재관주손상모형조(MIRI)(n=10)、곡미타진저제량조(n=l0)、곡미타진고제량조(n=10),여10지위가수술조.제작재관주손상모형후,관찰각조대서혈류동역학변화,측정종류배사인자-α(TNF-α)、백세포개소-6(IL-6)수평화관찰광경、전경하심기조직절편.결과 (1)각조대서혈류동역학지표비교:여가수술조[좌심실수축압(LVSP)(198±35.5)mmHg,좌심실서장말압(LVEDP) (17 ±9.18) mmHg,좌심실내압최대상승속솔(+dp/dtmax)(11050±1517.4) mmHg/s,좌심실내압최대하강속솔(-dp/dtmax)(9175±1900) mmHg/s]비교,모형조[LVSP(143±24.5)mmHg,LVEDP(37.5±7.16) mmHg,+dp/dtmax(7450±1755.1) mmHg/s,-dp/dtmax(6075±1641) Hg/S]、곡미타진저제량조[LVSP(154.5±31.1) mmHg,LVEDP(31.3±12.6)mmHg,+dp/dtmax(8527.7±2251.5) mmHg/s,-dp/dtmax(6694±2242.2)mmHg/s]、곡미타진고제량조[LVSP(168.3±17.6) mmHg,LVEDP(28±10.05) mmHg,+ dp/dtmax (9213.6±1747) mmHg/s,-dp/dtmax(7568±1462.4) mmHg/s]대서적LVEDP명현승고,LVSP、+dp/dtmax、-dp/dtmax명현감소;여모형조상비,곡미타진고제량조LVEDP명현감저,+dp/dtmax、-dp/dtmax명현증가,차이구유통계학의의(P＜0.01).(2)각조대서양화응격손상적비교:여가수술조[IL-6(2556.5±662.9)ng/ml,TNF-α(134±73.7) ng/ml]비교,모형조[IL-6(3664.0±995.7) ng/ml,TNF-α(443 ±22.1)ng/ml]、곡미타진저제량조[IL-6(3692.8±1545.2) ng/ml,TNF-α(295±24.2)ng/ml]、곡미타진고제량조[IL-6 (2654.8±681.7) ng/ml,TNF-α(230 ±7.8)ng/ml]대서TNF-α、IL-6수평명현증고;여모형조상비,곡미타진고제량조TNF-α、IL-6수평명현감저,차이구유통계학의의(P＜0.01).(3)광경급전경하관찰:제가수술조대서외각조대서균유불동정도손상,곡미타진고제량조손상교경.결론 곡미타진고제량대대서심기결혈재관주손상유보호작용.
Objeetive To investigate protective effect of trimetazidine on myocardial ischemia/reperfusion injury (MIRI) in rats.Methods Forty Wistar rats were randomly divided into MIRI group (n =10 rats),trimetazidine high-dosage group (n =10 rats; 20 mg/kg),trimetazidine low-dosage group (n=10 rats; 10 mg/kg),and the normal control group (n =10 rats).After MIRI,hemodynamic changes were observed,the concentration of IL-6 and TNF-α was determined,and the cardiac muscle histology under the microscope was observed.Results Hemodynamic studies:Compared to the indices LVSP(198 ±35.5) mmHg,LVEDP (17 ±9.18) mmHg,+ dp/dt max (11050 ± 1517.4) mmHg/s,and-dp/dtmax (9175± 1900) mmHg/s] in the sham-operated group,the indices [LVSP (143 ± 24.5) mmHg,LVEDP (37.5 ±7.16)mmHg,+ dp/dtmax (7450 ± 1755.1) mmHg/s,and-dp/dtmax (6075 ± 1641) Hg/S] in the MIRI group,the indices [LVSP (154.5 ± 31.1) mmHg,LVEDP (31.3 ± 12.6) mmHg,± dp/dtmax (8527.7 ±2251.5) mmHg/s,and-dp/dtmax (6694 ± 2242.2) mmHg/s] in the trimetazidine low-dosage (10 mg/kg)group,the indices[LVSP (168.3 ± 17.6) mmHg,LVEDP (28 ± 10.05) mmHg,+ dp/dtmax (9213.6 ±1747) mmHg/s,and-dp/dtmax (7568 ± 1462.4) mmHg/s] in the trimetazidine high-dosage (20 mg/kg)group,left ventricular remodeling end diastolic pressure (LVEDP),left ventricular systolic pressure (LVSP),and left ventricular pressure maxial rate of rise and fall (± dp/dtmax) were significantly decreased.Compared to the MIRI group,LVSP and ± dp/dtmax in the trimetazidine high-dosage (20 mg/kg)group were significantly increased (P ＜ 0.01),and myocardial damage of MIRI group was more severe in microscope.Compared to the sham-operated group [IL-6 (2556.5 ± 662.9) ng/ml,and TNF-α (134 ± 73.7)ng/ml],the corresponding indices [IL-6 (3664.0 ± 995.7) ng/ml,and TNF-α (443 ± 22.1) ng/ml] in the MIRI group,[IL-6 (3692.8 1545.2) ng/ml,and TNF-α (295 ± 24.2) ng/ml] in the trimetazidiue low-dosage (10 mg/kg) group,and[IL-6(2654.8 ±681.7) ng/ml,and TNF-α(230 ±7.8) ng/ml]in the trimetazidine high-dosage (20 mg/kg) group,the levels of IL-6 and TNF-α were significantly increased.Compared to the MIRI group,the levels of IL-6 and TNF-α were significantly decreased in the trimetazidine high-dosage (20 mg/kg) group (P ＜ 0.01).Conclusions The high-dosage (20 mg/kg) of trimetazidine had a protective effect on myocardial ischemia-reperfusion injury.