CAJ | 학술논문

目的探讨持续输注不同剂量异丙肾上腺素(ISO)对早期脓毒症大鼠心肌线粒体的保护作用及其机制.方法 30只SD雄性大鼠按随机数字表法分为5组(每组各6只):对照组,内毒素组和ISO低、中、高剂量组.内毒素组腹腔注射脂多糖(LPS)10 mg/kg同时持续输注9 g/L盐水1 mL/h;ISO低、中、高剂量组腹腔注射LPS 10 mg/kg同时分别持续输注ISO 0.06、0.30和0.60μg/(kg· min);对照组腹腔注射同时持续输注与其他组等体积的9 g/L盐水.腹腔注射9g/L盐水或LPS后24h检测血清肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)、心肌线粒体氧化氮化应激水平和线粒体肿胀度,并观察心肌组织病理改变(HE染色)和线粒体形态学改变.结果与对照组比较,内毒素组CK、CK-MB、一氧化氮(NO)含量、诱导型一氧化氮合酶(iNOS)活力和丙二醛(MDA)含量均升高(P均＜0.05),超氧化物歧化酶(SOD)活力降低[(11.543±1.080) U/mg prot比(9.892±0.815) U/mg prot,P＜0.05];HE染色示心肌组织呈炎症改变;线粒体超微结构异常(线粒体肿胀等).ISO干预使CK和CK-MB水平及心肌线粒体肿胀度降低(P均＜0.05),SOD活力升高(P均＜0.05);低剂量组NO含量、iNOS活力和MDA含量降低[(10.823±2.240) μmol/g prot比(7.917±2.203) μmol/g prot,(0.045±0.008) U/mg prot比(0.033 ±0.003) U/mg prot,(1.663 ±0.618) mmol/mg prot比(0.768±0.312)mmol/mg prot,P均＜0.05],中、高剂量组iNOS活力和MDA含量升高(P均＜0.05);与中剂量组相比,高剂量组肿胀度升高(1.160±0.186比1.393±0.128,P＜0.05).结论脓毒症早期大鼠心肌和心肌线粒体受损,持续低剂量ISO输注对心肌线粒体具有保护作用,其机制可能与氧化氮化应激水平降低有关.
목적 탐토지속수주불동제량이병신상선소(ISO)대조기농독증대서심기선립체적보호작용급기궤제.방법 30지SD웅성대서안수궤수자표법분위5조(매조각6지):대조조,내독소조화ISO저、중、고제량조.내독소조복강주사지다당(LPS)10 mg/kg동시지속수주9 g/L염수1 mL/h;ISO저、중、고제량조복강주사LPS 10 mg/kg동시분별지속수주ISO 0.06、0.30화0.60μg/(kg· min);대조조복강주사동시지속수주여기타조등체적적9 g/L염수.복강주사9g/L염수혹LPS후24h검측혈청기산격매(CK)화기산격매동공매(CK-MB)、심기선립체양화담화응격수평화선립체종창도,병관찰심기조직병리개변(HE염색)화선립체형태학개변.결과 여대조조비교,내독소조CK、CK-MB、일양화담(NO)함량、유도형일양화담합매(iNOS)활력화병이철(MDA)함량균승고(P균＜0.05),초양화물기화매(SOD)활력강저[(11.543±1.080) U/mg prot비(9.892±0.815) U/mg prot,P＜0.05];HE염색시심기조직정염증개변;선립체초미결구이상(선립체종창등).ISO간예사CK화CK-MB수평급심기선립체종창도강저(P균＜0.05),SOD활력승고(P균＜0.05);저제량조NO함량、iNOS활력화MDA함량강저[(10.823±2.240) μmol/g prot비(7.917±2.203) μmol/g prot,(0.045±0.008) U/mg prot비(0.033 ±0.003) U/mg prot,(1.663 ±0.618) mmol/mg prot비(0.768±0.312)mmol/mg prot,P균＜0.05],중、고제량조iNOS활력화MDA함량승고(P균＜0.05);여중제량조상비,고제량조종창도승고(1.160±0.186비1.393±0.128,P＜0.05).결론 농독증조기대서심기화심기선립체수손,지속저제량ISO수주대심기선립체구유보호작용,기궤제가능여양화담화응격수평강저유관.
Objective To investigate the protective effect of continuous intravenous infusion of Isoproterenol (ISO)on myocardial mitochondria of early septic rats and the corresponding mechanism.Methods Thirty Sprague Dawley (SD)rats were randomly divided into 5 groups (6 cases per group):control group,endotoxin group,ISO small-dose group,ISO medium-dose group and ISO large-dose group.Endotoxin group and ISO intervene group received same management apart from drug intervention:receiving intravenous injection of lipopolysaccharide (LPS)10 mg/kg followed by an continuous intravenous infusion of 9 g/L saline 1 mL/h or ISO 0.06 μg/(kg · min),0.30 μg/(kg · min)and 0.60 μg/(kg · min).Control group received intraperitoneal injection and continuous intravenous infusion with the same amount of 9 g/L saline.The primary endpoint of the study was 24 hours after injection of 9 g/L saline or LPS.Serum creatine kinase (CK) and creatine kinase isoenzyme (CK-MB),oxidative and nitrosative stress levels and swelling of isolated heart mitochondrion were detected.The pathological changes of the myocardium and morphologic changes of the heart mitochondria were observed through light microscope and scanning electron microscope,respectively.Results The levels of CK,CK-MB,nitric oxide (NO) content,inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA)content in endotoxin group were increased compared with control group (all P ＜ 0.05),while the superoxide dismutase (SOD) activity decreased [(11.543 ± 1.080) U/mg prot vs (9.892 ±0.815) U/mg prot,P ＜0.05].The morphology of the heart mitochondria significantly changed (such as swelling,disordered arrangement,crest fracture,fusion and cavitations,and so on).ISO intervention significantly decreased the levels of CK,CK-MB and mitochondrial swelling (all P ＜ 0.05) and increased the SOD activity (all P ＜ 0.05).The levels of NO content,iNOS activity and MDA content were significantly decreased in small-dose group [(10.823 ± 2.240) μmol/g prot vs (7.917 ± 2.203) μmol/g prot,(0.045 ± 0.008) U/mg prot vs (0.033 ± 0.003) U/mg prot,(1.663 ± 0.618) mmol/mg prot vs (0.768 ± 0.312) mmol/mg prot,all P ＜ 0.05],while the levels of iNOS activity and MDA content were significantly increased in medium-and large-dose group (all P ＜ 0.05) ; compared with medium-dose group,the degree of mitochondrial swelling in large-dose group increased (1.160 ± 0.186 vs 1.393 ± 0.128,P ＜ 0.05).The pathological changes of the myocardium mitochondria significantly improved.Conclusions The myocardium and myocardial mitochondria of early septic rats were damaged,continuous intravenous infusion of low-dose ISO revealed protective effect on these damages,and the corresponding mechanism may relate to the decrease of the oxidative and nitrosative stress.