尼可地尔对力竭运动大鼠心肌损伤的保护作用研究

Protective effect of nicorandil against exhausted exercise inducedmyocardial injury in rats

目的探讨不同剂量尼可地尔对一次性力竭运动大鼠心肌损伤的影响。方法雄性SD大鼠35只随机分为5组:对照组、力竭组、尼可地尔低剂量组[1 mg/(kg·d)]、尼可地尔中剂量组[3 mg/(kg·d)]、尼可地尔高剂量组[9 mg/(kg·d)]。不同剂量尼可地尔组给予尼可地尔灌胃4周,对照组和力竭组予以等渗盐水3 mg/(kg·d)灌胃4周。除对照组外,其余各组预处理后均行一次性力竭运动。电镜下观察组织病理学改变,检测血清天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)和心肌肌钙蛋白I(cTnI)活性,血浆去甲肾上腺素(NE)、肾上腺素(E)、多巴胺(DA)等儿茶酚胺(CA)水平,血清丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性以及心肌组织ATP含量。结果电镜下力竭组大鼠心肌线粒体嵴断裂,空泡变性,部分重度水肿,肌节紊乱,尼可地尔组线粒体损伤程度较轻,尼可地尔中剂量和高剂量组改善最为明显。力竭组血浆CA水平分别为NE(4185.28±683.48)pg/mL,E(4119.34±766.76)pg/mL,DA(814.03±411.02)pg/mL,血清cTnI(18.65±4.41)ng/mL,较对照组[分别为NE(739.50±336.68)pg/mL,E(2225.81±442.77)pg/mL,DA(95.11±23.44)pg/mL,cTnI(0.65±0.25)ng/mL]明显升高(P<0.05)。力竭组较对照组心肌组织ATP含量[(283.19±128.35)vs(509.21±76.18)μmol/g]明显降低,血浆SOD活性[(402.88±53.94)vs(528.81±76.98)U/mL]降低,MDA水平[(11.34±2.44)vs(4.68±0.41)nmol/mL]明显升高(P<0.05)。尼可地尔低、中、高剂量组血清cTnI均低于力竭组(P<0.05)。尼可地尔低、中、高剂量组NE水平均低于力竭组,尼可地尔高剂量组E和DA水平低于力竭组(P<0.05)。尼可地尔中、高剂量组ATP含量[分别为(310.71±74.12)μmol/g和(312.01±101.07)μmol/g]高于力竭组,但仅尼可地尔中剂量组差异有统计学意义(P<0.05)。结论力竭运动导致心肌超微结构损伤,但尼可地尔能减轻心肌损伤,其机制可能与降低氧化应激损伤和儿茶酚胺水平,提高心肌组织ATP含量有关。结论力竭运动导致心肌超微结构损伤,但尼可地尔能减轻心肌损伤,其机制可能与降低氧化应激损伤和儿茶酚胺水平,提高心肌组织ATP含量有关。

Objective To investigate the effects of different doses of nicorandil on myocardial injury in rats after exhaustive exercise.Methods Thirty-five male Sprague Dawley rats were randomly divided into 5 groups:control group,exhaustive exercise group,low-dose nicorandil group[1 mg/(kg·d)],medium-dose nicorandil group[3 mg/(kg·d)],high-dose nicorandil group[9 mg/(kg·d)].Nicorandil groups were given different doses of nicorandil while control group and exhaustive exercise group were given saline[3 mg/(kg·d)]by gavage for 4 weeks.Except for the control group,the other groups were given one-time exhaustive exercise after pretreatment.Histopathological changes were observed under electron microscope.The activities of serum aspartate aminotransferase(AST),lactate dehydrogenase(LDH),creatine kinase(CK),creatine kinase isoenzyme(CK-MB)and cardiac troponin I(cTnI),plasma catecholamine(CA)levels such as adrenaline(E),norepinephrine(NE),dopamine(DA),the content of serum malondialdehyde(MDA),the activity of superoxide dismutase(SOD),and the content of ATP in myocardial tissue were detected.Results Under an electron microscope,mitochondrial cristae were broken.Vacuolar degeneration,some severe edema and sarcomere disorder were found in exhausted group.The damage degree of mitochondria in nicorandil group was milder,and the improvement was most obvious in medium-dose nicorandil group and high-dose nicorandil group.The levels of plasma CA and cTnI in exhaustive exercise group were significantly higher than those in control group,NE(4185.28±683.48)vs(739.50±336.68)pg/mL,E(4119.34±766.76)vs(2225.81±442.77)pg/mL,DA(814.03±411.02)vs(95.11±23.44)pg/mL,cTnI(18.65±4.41)vs(0.65±0.25)ng/mL,respectively(P<0.05).Compared with control group,the content of ATP in exhaustive exercise group was significantly decreased[(283.19±128.35)vs(509.21±76.18)μmol/g],the activity of SOD was decreased[(402.88±53.94)vs(528.81±76.98)U/mL],and the level of MDA was significantly increased[(11.34±2.44)vs(4.68±0.41)nmol/mL](all P<0.05).The serum cTnI of low,medium and high dose nicorandil groups were(10.86±3.61)ng/mL,(9.57±2.78)ng/mL and(10.15±2.27)ng/mL respectively,which were significantly lower than those of exhaustive exercise group(all P<0.05).The levels of CA in high-dose nicorandil group were significantly lower than those in exhaustive exercise group[NE(1856.81±964.98)pg/mL,E(3384.27±956.33)pg/mL and DA(421.47±194.43)pg/mL,all P<0.05].The ATP contents of medium-dose and high-dose nicorandil group were(310.71±74.12)μmol/g and(312.01±101.07)μmol/g respectively,which were higher than that of exhaustive exercise group.The difference was significant in medium-dose nicorandil group(P<0.05).Conclusion Exhaustive exercise leads to myocardial ultrastructural damage,increase of myocardial enzymes and CA levels,and decrease of myocardial ATP content.Nicorandil can alleviate myocardial injury,which may be related to the decrease of oxidative stress injury and catecholamine level,and increase of myocardial ATP content.