经胃肠道给予氯化血红素对压力负荷性心衰大鼠氧化应激状态的影响
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Effect of gastrointestinal administration of hemin on oxidative stress in rat model of heart failure induced by pressure-overload
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    摘要:

    目的探讨经胃肠道给予氯化血红素后体内血红素氧合酶-1(HO-1)-CO-胆红素的反应和对大鼠慢性压力负荷性心力衰竭进程中氧化应激的影响。方法成年雄性SD大鼠63只,随机分为血红素组、心衰组和对照组,每组21只,各组再分为4、8、12周三个小组,每小组7只。心衰组、氯化血红素组行腹主动脉缩窄术,对照组行假手术。从术后3周开始血红素组以60mg/(kg·d)氯化血红素灌胃,对照组和心衰组同时间灌以同体积生理盐水。各小组在相应的时间点检测血清HO-1、碳氧血红蛋白(COHb)、丙二醛(MDA)、氧化低密度脂蛋白(ox-LDL)的含量,检测血清超氧化物歧化酶(SOD)的活性。结果 (1)氯化血红素组在给药后4、8、12周血清HO-1含量明显高于心衰组,分别是(6.80±0.92)μg/Lvs(2.5±0.22)μg/L;(10.70±0.69)μg/Lvs(4.50±0.28)μg/L;(13.30±0.99)μg/Lvs(6.07±0.71)μg/L(P<0.01);COHb含量均明显高于心衰组,分别为(4.34±0.31)%vs(1.68±0.11)%;(6.32±0.44)%vs(2.46±0.20)%;(7.80±0.39)%vs(3.01±0.42)%(P<0.01)。(2)氯化血红素组在给药4、8、12周血清MDA含量均低于心衰组,分别为(8.3±1.3)μmol/Lvs(14.2±2.3)μmol/L(P<0.05);(9.6±0.5)μmol/Lvs(20.2±3.2)μmol/L(P<0.01);(11.8±1.1)μmol/Lvs(26.1±3.7)μmol/L(P<0.01);(3)氯化血红素组SOD活性在4、8、12周均高于心衰组,分别是(125±6)kU/Lvs(95±10)kU/L(P<0.01);(109±9)kU/Lvs(67±5)kU/L(P<0.01);(72±10)kU/Lvs(40±6)kU/L(P<0.01)。(4)氯化血红素组ox-LDL含量在4、8、12周均低于心衰组,分别为(1.14±0.16)μmol/Lvs(1.80±0.22)μmol/L;(1.38±0.14)μmol/Lvs(2.34±0.25)μmol/L;(1.83±0.16)μmol/Lvs(3.17±0.31)μmol/L(均P<0.01)。结论经胃肠道给予氯化血红素可以对体内的HO-1产生诱导作用;HO/CO-胆红素系统的诱导可改善压力负荷心衰大鼠的体内氧化/抗氧化失衡状态。

    Abstract:

    Objective To investigate the effect of gastrointestinal administration of hemin on oxidative stress in rat model of heart failure induced by pressure-overload. Methods Sixty-three adult male Sprague-Dawley rats were divided into control group (group C),heart failure group (HF group) and hemin group (Hm group) randomly,with 21 in each group. Each group was further divided into three subgroups (n=7) for the time of 4 weeks,8 weeks and 12 weeks after heart failure established. The rats in HF and Hm groups were subjected to surgical abdominal aorta constriction,while rats in control group to sham operation. At 3 weeks after surgery,rats in Hm group received daily gastric administration of hemin (60 mg/kg),while rats in HF and control groups received equal volume of normal saline. At each time points,the plasma levels of heme oxygenase-1 (HO-1),carboxyhemoglobin(COHb),malondialdehyde (MDA),oxidized low density lipoprotein (ox-LDL),and the activity of superoxide dismutase(SOD) were detected. Results (1) Compared with HF group,the plasma levels of HO-1 and COHb in Hm group were obviously increased at each time points HO-1: (6.80±0.92) μg/L vs (2.50±0.22) μg/L;(10.70±0.69) μg/L vs (4.50±0.28) μg/L;and (13.30±0.99) μg/L vs (6.07±0.71) μg/L,P<0.01; COHb: (4.34±0.31)% vs (1.68±0.11)%;(6.32±0.44)% vs (2.46±0.20) %;and (7.80±0.39)% vs (3.01±0.42)%,P<0.01. (2) Compared with HF group,the MDA levels were obviously decreased in Hm group at each time points (8.3±1.3) μmol/L vs (14.2±2.3) μmol/L,P<0.05;(9.6±0.5) μmol/L vs (20.2±3.2) μmol/L,P<0.01;and (11.8±1.1) μmol/L vs (26.0±3.7) μmol/L,P<0.01. (3) SOD activity was higher in Hm group than in HF group at each time points (125±6) kU/L vs (95±10) kU/L,P<0.01;(109±9) kU/L vs (67±5) kU/L,P<0.01;and (72±10) kU/L vs (40±6) kU/L,P<0.01. (4)The content of ox-LDL was lower in Hm group than in HF group at each time points (1.14±0.16) μmol/L vs (1.80±0.22) μmol/L,(1.38±0.14) μmol/L vs (2.34±0.25) μmol/L,and (1.83±0.16) μmol/L vs (3.17±0.31) μmol/L,P<0.01. Conclusion Production of HO-1 can be induced by gastrointestinal administration of hemin. The induction of HO-1/CO-bilirubin system may correct the in vivo unbalance of oxidation/antioxidation in HF rat induced by pressure-overload.?更多

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SI XiaoYun, CHENG YouQIN, LI XiaoYing, et al.经胃肠道给予氯化血红素对压力负荷性心衰大鼠氧化应激状态的影响[J].中华老年多器官疾病杂志,2010,9(3):268~271

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