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槲皮素和谷胱甘肽对NG-硝基-L-精氨酸甲酯诱导的子痫前期大鼠模型中超氧化物歧化酶、过氧化氢酶、丙二醛水平、血压及新生儿结局的影响

Effect of quercetine and glutathione on the level of superoxide dismutase, catalase, malonyldialdehyde, blood pressure and neonatal outcome in a rat model of pre-eclampsia induced by NG-nitro-L-arginine-methyl ester.

作者信息

Tanir H Mete, Sener Turgay, Inal Mine, Akyuz Fahrettin, Uzuner Kubilay, Sivri Ergul

机构信息

Department of Obstetrics and Gynaecology, Osmangazi University Faculty of Medicine, Division of Maternal and Fetal Medicine, Meselik Kampusu 26480, Eskisehir, Turkey.

出版信息

Eur J Obstet Gynecol Reprod Biol. 2005 Feb 1;118(2):190-5. doi: 10.1016/j.ejogrb.2004.04.033.

DOI:10.1016/j.ejogrb.2004.04.033
PMID:15653201
Abstract

OBJECTIVE

To anticipate the impact of antioxidant use on lipid peroxidation products, free oxygen radical scavengers, blood pressure (BP), proteinuria and neonatal outcome (as seen in percentage survival, litter birth weight) in a rat model of pre-eclampsia induced by NG-nitro-L-arginine-methyl-ester (L-NAME), an inhibitor of nitric oxide synthase (NOS).

MATERIAL AND METHODS

Female adult non-pregnant Sprague-Dawley rats (n=40) with timed pregnancies were allocated into four groups according to medication they received on day 17 to term. Rats were randomised into a sham-treated group (group I, n=10) and groups treated with L-NAME, 50 mg/day i.p., only (group II, n=10), L-NAME + quercetine, 10mg/kg i.p. (group III, n=10) and L-NAME + glutathione, 60 mg/kg i.p. (group IV, n=10). Blood levels of superoxide dismutase (SOD), catalase (CAT) and malonyldialdehyde (MDA) were assessed on day 22 of gestation. Intracardiac blood sampling and hysterotomy were performed on day 22 of gestation. Mean systolic BP (measured with a tail-cuff device), level of proteinuria, total urine output, pups birth weight and percentages of live and of dead pups were recorded.

RESULTS

Mean systolic BP and SOD, CAT and MDA levels were higher in rats infused with L-NAME than in the sham-treated group. In group IV, SOD levels were lower than in group II (P <0.001). A linear positive correlation between BPs on day 20 and SOD levels (rp=0.39) was recorded, as were negative correlations between level of proteinuria and SOD levels (rp=-0.39) and between CAT and MDA levels (rp=-0.39). Birth weights were higher in the sham-treated group than in the other groups (P <0.001). Pups of hypertensive gravid rats treated with antioxidants had better survival rates than those of rats in group II and the sham-treated group (Chi-square=15.9, d.f.: 3, P <0.01).However, no correlation was detected between higher pup mortality rate and birth weight of pups.

CONCLUSION

In this rat model of pre-eclampsia, adverse outcomes, such as proteinuria and high neonatal death rate, are reversed by exogenous antioxidant use, even though no significant improvement is detected in terms of BP and birth weight of pups.

摘要

目的

在由一氧化氮合酶(NOS)抑制剂NG-硝基-L-精氨酸甲酯(L-NAME)诱导的子痫前期大鼠模型中,预测抗氧化剂的使用对脂质过氧化产物、游离氧自由基清除剂、血压(BP)、蛋白尿和新生儿结局(如存活率、窝产仔体重)的影响。

材料与方法

将40只成年未孕且有定时妊娠的雌性Sprague-Dawley大鼠,根据其在妊娠第17天至足月所接受的药物治疗分为四组。大鼠被随机分为假手术组(I组,n = 10)和仅接受腹腔注射50mg/天L-NAME的组(II组,n = 10)、腹腔注射10mg/kg槲皮素的L-NAME + 槲皮素组(III组,n = 10)以及腹腔注射60mg/kg谷胱甘肽的L-NAME + 谷胱甘肽组(IV组,n = 10)。在妊娠第22天评估超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和丙二醛(MDA)的血液水平。在妊娠第22天进行心脏采血和子宫切开术。记录平均收缩压(用尾袖装置测量)、蛋白尿水平、总尿量、幼崽出生体重以及存活和死亡幼崽的百分比。

结果

注射L-NAME的大鼠的平均收缩压以及SOD、CAT和MDA水平高于假手术组。在IV组中,SOD水平低于II组(P <0.001)。记录到妊娠第20天的血压与SOD水平之间呈线性正相关(rp = 0.39),蛋白尿水平与SOD水平之间以及CAT和MDA水平之间呈负相关(rp = -0.39)。假手术组的出生体重高于其他组(P <0.001)。用抗氧化剂治疗的高血压妊娠大鼠的幼崽存活率高于II组和假手术组的大鼠(卡方检验= 15.9,自由度:3,P <0.01)。然而,未检测到较高的幼崽死亡率与幼崽出生体重之间的相关性。

结论

在这个子痫前期大鼠模型中,尽管在血压和幼崽出生体重方面未检测到显著改善,但外源性抗氧化剂的使用可逆转蛋白尿和高新生儿死亡率等不良结局。

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