NF-κB在大鼠妊娠糖尿病中介导氧化应激反应的机制研究
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摘要
目的探究核因子κB(NF-κB)在大鼠妊娠糖尿病中介导氧化应激反应的分子机制。方法通过构建妊娠糖尿病大鼠模型,获36只孕鼠随机分为NF-κB抑制剂PDTC组(PDTC组)、妊娠期高血糖组(GDM组)和正常妊娠组(对照组)。采用比色法检测各组大鼠胎盘组织匀浆中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力以及活性氧(ROS)水平,采用蛋白免疫印迹的方法检测各组大鼠胎盘组织匀浆中相关蛋白SOD、NF-κB-p65的表达水平。结果与对照组比较,GDM组中MDA含量升高,SOD活力降低,ROS水平升高,差异均有统计学意义(t分别=-7.23、6.88、-7.59,P均<0.05);与GDM组比较,PDTC组MDA含量降低,SOD活力升高,ROS水平降低,差异均有统计学意义(t分别=2.47、-3.04、3.01,P均<0.05)。与对照组比较,GDM组中NF-κB-p65表达水平升高,SOD表达水平降低,差异均有统计学意义(t分别=-4.35、9.69,P均<0.05);与GDM组比较,PDTC组中NF-κB-p65表达水平降低,SOD表达水平升高,差异均有统计学意义(t分别=9.89、-5.73,P均<0.05)。结论妊娠糖尿病中发生氧化损伤,并且激活了NF-κB通路,抑制NF-κB可改善妊娠糖尿病中发生的氧化损伤。
Objective To explore the molecular mechanism of nuclear factor-kappa B(NF-κB)mediating oxidative stress in gestational diabetes mellitus in rats.Methods Totally 36 pregnant rats that molded by gestational diabetes mellitus were randomly divided into NF-κB inhibitor PDTC group(PDTC group),gestational diabetes mellitus group(GDM group)and normal pregnancy group(control group).The malondialdehyde(MDA),superoxide dismutase(SOD)activity and reactive oxygen species(ROS)level in the placental tissue homogenate of each group were detected by colorimetry,and expression level of SOD and NF-κB-p65 were detected by Western blotting.Results Compared with the control group,the MDA content of the GDM group increased,the SOD activity decreased,and the ROS level increased.The differences were statistically significant(t=-7.23,6.88,-7.59,P<0.05).Compared with the GDM group,the MDA content of the PDTC group decreased,the SOD activity increased,and the ROS level decreased.The differences were statistically significant(t = 2.47,-3.04,3.01,P<0.05).Compared with the control group,the expression of NF-κB-p65 was increased in the GDM group,and the expression level of SOD was decreased.The differences were statistically significant(t=-4.35,9.69,P<0.05).Compared with the GDM group,the expression level of NF-κB-p65 was decreased and the expression level of SOD was increased in the PDTC group(t = 9.89,-5.73,P<0.05).Conclusion Oxidative damage occurs in gestational diabetes mellitus,and the NF-κB pathway is activated.Inhibition of NF-κB can improve oxidative damage in gestational diabetes mellitus.
Objective To explore the molecular mechanism of nuclear factor-kappa B(NF-κB)mediating oxidative stress in gestational diabetes mellitus in rats.Methods Totally 36 pregnant rats that molded by gestational diabetes mellitus were randomly divided into NF-κB inhibitor PDTC group(PDTC group),gestational diabetes mellitus group(GDM group)and normal pregnancy group(control group).The malondialdehyde(MDA),superoxide dismutase(SOD)activity and reactive oxygen species(ROS)level in the placental tissue homogenate of each group were detected by colorimetry,and expression level of SOD and NF-κB-p65 were detected by Western blotting.Results Compared with the control group,the MDA content of the GDM group increased,the SOD activity decreased,and the ROS level increased.The differences were statistically significant(t=-7.23,6.88,-7.59,P<0.05).Compared with the GDM group,the MDA content of the PDTC group decreased,the SOD activity increased,and the ROS level decreased.The differences were statistically significant(t = 2.47,-3.04,3.01,P<0.05).Compared with the control group,the expression of NF-κB-p65 was increased in the GDM group,and the expression level of SOD was decreased.The differences were statistically significant(t=-4.35,9.69,P<0.05).Compared with the GDM group,the expression level of NF-κB-p65 was decreased and the expression level of SOD was increased in the PDTC group(t = 9.89,-5.73,P<0.05).Conclusion Oxidative damage occurs in gestational diabetes mellitus,and the NF-κB pathway is activated.Inhibition of NF-κB can improve oxidative damage in gestational diabetes mellitus.
引文
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6刘眉,王兴和,张铭承,等.妊娠期糖尿病的复发率、复发的危险因素及复发性妊娠期糖尿病母婴预后的分析[J].医学临床研究,2018,35(5):845-848.
7徐静,滕玉翠,张静,等.妊娠合并糖尿病治疗对母婴预后的影响探究[J].中国妇幼健康研究,2017,28(S1):41-42.
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11范敏,周敏,董世庆,等.芒果苷对妊娠期糖尿病大鼠抗氧化能力的影响[J].临床和实验医学杂志,2017,16(10):942-946.
12张雪,邢宝恒,曹亚磊,等.白藜芦醇对妊娠期糖尿病大鼠肾脏组织抗氧化和抗炎的作用[J].中国实验方剂学杂志,2017,23(2):131-137.
13陈龙,汪秋伟,孙金华,等.维生素E对妊娠期糖尿病小鼠氧化应激及炎症因子的影响[J].卫生研究,2017,46(3):488-489.
14王海蓉.核因子-κB与氧化应激[J].心血管病学进展,2002,23(3):166-170.
15杨静,赵亚宁,杨永康.不同来源胰岛素治疗对妊娠期糖尿病孕妇TLR4乙酰化及NF-κB p65表达的影响[J].中国妇幼保健,2017,32(19):4646-4648.
16胡丽梅,秦淑芬,姜保慧,等.葛根素联合门冬胰岛素对妊娠期糖尿病患者TLR4/NF-κB炎症信号通路及脂肪因子的影响[J].河北医药,2016,38(16):2443-2446.
2李玉琴.妊娠期糖尿病的规范化治疗对妊娠结局的影响[J].中国现代医学杂志,2018,28(7):124-126.
3苗志荣,吴红花.妊娠期糖尿病诊断与治疗研究进展[J].中国糖尿病杂志,2017,25(4):365-370.
4 Sudharshana KM,Bhandiwada A,Chandan SL,et al.Evaluation of oxidative stress and proinflammatory cytokines in gestational diabetes mellitus and their correlation with pregnancy outcome[J].Indian J Endocrinol Metab,2018,22(1):79-84.
5 Usluo ullari B,Usluogullari CA,Balkan F,et al.Role of serum levels of irisin and oxidative stress markers in pregnant women with and without gestational diabetes[J].Gynecol Endocrinol,2017,33(5):1-3.
6刘眉,王兴和,张铭承,等.妊娠期糖尿病的复发率、复发的危险因素及复发性妊娠期糖尿病母婴预后的分析[J].医学临床研究,2018,35(5):845-848.
7徐静,滕玉翠,张静,等.妊娠合并糖尿病治疗对母婴预后的影响探究[J].中国妇幼健康研究,2017,28(S1):41-42.
8 Rochette L,Zeller M,Cottin Y,et al.Diabetes,oxidative stress and therapeutic strategies[J].Biochim Biophys Acta,2014,1840(9):2709-2729.
9 Newsholme P,Cruzat VF,Keane KN,et al.Molecular mechanisms of ROS production and oxidative stress in diabetes[J].Biochem J,2016,473(24):4527-4550.
10马骋,阮清伟,俞卓伟.氧化应激与免疫衰老[J].中华老年医学杂志,2017,36(2):224-228.
11范敏,周敏,董世庆,等.芒果苷对妊娠期糖尿病大鼠抗氧化能力的影响[J].临床和实验医学杂志,2017,16(10):942-946.
12张雪,邢宝恒,曹亚磊,等.白藜芦醇对妊娠期糖尿病大鼠肾脏组织抗氧化和抗炎的作用[J].中国实验方剂学杂志,2017,23(2):131-137.
13陈龙,汪秋伟,孙金华,等.维生素E对妊娠期糖尿病小鼠氧化应激及炎症因子的影响[J].卫生研究,2017,46(3):488-489.
14王海蓉.核因子-κB与氧化应激[J].心血管病学进展,2002,23(3):166-170.
15杨静,赵亚宁,杨永康.不同来源胰岛素治疗对妊娠期糖尿病孕妇TLR4乙酰化及NF-κB p65表达的影响[J].中国妇幼保健,2017,32(19):4646-4648.
16胡丽梅,秦淑芬,姜保慧,等.葛根素联合门冬胰岛素对妊娠期糖尿病患者TLR4/NF-κB炎症信号通路及脂肪因子的影响[J].河北医药,2016,38(16):2443-2446.