L-抗坏血酸通过抑制皮层神经元/胶质细胞共培养物中的MAPK激活和NF-κB易位来减弱内毒素诱导的炎症介质的产生。
L-Ascorbate Attenuates the Endotoxin-Induced Production of Inflammatory Mediators by Inhibiting MAPK Activation and NF-κB Translocation in Cortical Neurons/Glia Cocultures
抽象
响应于对中枢神经系统的急性损伤(例如病原体入侵或神经元损伤),神经胶质细胞被激活并分泌炎性介质,例如一氧化氮(NO),细胞因子和趋化因子。这种神经炎症在慢性神经退行性疾病的病理生理中起着至关重要的作用。在败血性脑病患者中,内源性抗坏血酸水平显着降低。使用细菌内毒素脂多糖(LPS)在原代神经元/神经胶质共培养物中诱导神经炎症,我们研究了L-抗坏血酸(维生素C; V。C)如何影响神经炎症。 LPS(100 ng / ml)以时间依赖性方式诱导诱导型一氧化氮合酶(iNOS)的表达以及一氧化氮,白介素(IL)-6和巨噬细胞炎性蛋白2(MIP-2 / CXCL2)的产生;但是,与Vit共同治疗。 C(5或10 mM)减弱了LPS诱导的iNOS表达以及NO,IL-6和MIP-2的产生。免疫细胞化学染色后显示的形态特征证实为Vit。 C抑制LPS诱导的星形胶质细胞和小胶质细胞活化。因为Vit。 C可以通过钠依赖性Vit转运到神经元和神经胶质中。 C转运蛋白2,我们研究了维生素。 C影响神经元/神经胶质共培养物中LPS激活的细胞内信号传导。结果表明,LPS处理后,有丝分裂原激活的蛋白激酶(MAPK)(例如p38在30分钟时)和细胞外信号调节激酶(ERKs)在180分钟时增加了激活(由磷酸化引起)。 p38和ERK MAPK的抑制作用抑制LPS诱导的炎症介质的产生。维特C还抑制LPS诱导的p38和ERK的活化。维生素的联合治疗。与单独使用抑制剂相比,C和p38和ERK抑制剂没有产生其他抑制作用,表明Vit。 C通过与这些抑制剂相同的信号通路(即MAPK)起作用。维特C还减少了LPS诱导的IκB-α降解和NF-κB易位。因此,Vit。 C通过抑制MAPK和NF-κB信号通路,抑制LPS刺激的神经元/神经胶质共培养物中炎性介质的产生。
L-Ascorbate Attenuates the Endotoxin-Induced Production of Inflammatory Mediators by Inhibiting MAPK Activation and NF-κB Translocation in Cortical Neurons/Glia Cocultures
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0097276
槲皮素降低链脲佐菌素诱导的糖尿病大鼠肝脏的氧化应激,NF-κB活化和iNOS过表达
摘要
实验和临床研究中越来越多的证据表明,氧化应激与糖尿病组织损伤的发病机理和进展有关。这项研究调查了槲皮素(Quercetin)治疗对链脲佐菌素诱导的糖尿病大鼠的氧化应激,核因子(NF)-κB活化和诱导型一氧化氮合酶(iNOS)表达的保护作用。
将雄性Wistar大鼠分为4组:对照组,每天用槲皮素(150μmol/ kg,腹腔注射)治疗的对照组,未治疗的糖尿病大鼠和用槲皮素治疗的糖尿病大鼠。
糖尿病是由一次腹膜内链脲佐菌素streptozotocin(70 mg / kg)注射引起的。八周后,我们通过电泳迁移率测定法测量了肝脏中的TBARS和氢过氧化物引发的化学发光(QL)作为氧化应激的标志物,以及抗氧化酶过氧化氢酶,超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶的活性和Western blot检测IκB激酶(IKKα和IKKβ),抑制剂IκB(IκBα和IκBβ)和iNOS的表达和表达的NF-κB活化 。
糖尿病大鼠的血浆葡萄糖浓度显着增加,槲皮素未改变。链脲佐菌素的使用引起了肝中TBARS浓度,QL,SOD和过氧化氢酶活性的显着增加,而槲皮素阻止了这些活动。在链脲佐菌素治疗的大鼠中也观察到了NF-κB的活化,IKKα和iNOS蛋白水平的诱导以及IκBα降解的增加。槲皮素消除了所有这些作用。
这些发现表明,槲皮素治疗通过消除IKK /NF-κB信号转导途径,可能会阻止涉及早期糖尿病组织损伤发展和晚期并发症发展的有害介质的产生。
NOTE
链脲佐菌素streptozotocin是一种从无色链霉菌中提取的抗生素,目前已以高度纯化的形式在市场上出售,它是诱导实验性糖尿病的常用药物。在链脲佐菌素诱导的糖尿病大鼠中报道了
Magnolia officinalis。
链脲佐菌素或链脲佐菌素(INN,USP)(STZ)是一种天然存在的烷基化抗肿瘤药,对哺乳动物胰腺中产生胰岛素的β细胞特别有毒。它在医学上用于治疗朗格罕氏岛的某些癌症,并在医学研究中用于产生大剂量高血糖症动物模型以及2型糖尿病或...
Quercetin Decreases Oxidative Stress, NF-κB Activation, and iNOS
Overexpression in Liver of Streptozotocin-Induced Diabetic Rats
Increasing evidence in both experimental and clinical studies suggests that
oxidative stress is involved in the pathogenesis and progression of diabetic
tissue damage. This study investigated the protective effects of quercetin
treatment on oxidative stress, nuclear factor (NF)-κB activation and expression
of inducible nitric oxide synthase (iNOS) in streptozotocin-induced diabetic
rats. Male Wistar rats were divided into 4 groups: control rats, control rats
treated daily with quercetin (150 μmol/kg, i.p.), untreated diabetic rats, and
diabetic rats treated with quercetin. Diabetes was induced by a single i.p.
injection of streptozotocin (70 mg/kg). Eight weeks later we measured TBARS and
hydroperoxide-initiated chemiluminescence (QL) in liver as markers of oxidative
stress, and activities of the antioxidant enzymes catalase, superoxide dismutase
(SOD), and glutathione peroxidase, NF-κB activation by an electrophoretic
mobility shift assay and expression of IκB kinases (IKKα and IKKβ), the
inhibitor IκB (IκBα and IκBβ), and iNOS by Western blot. The plasma glucose
concentration was significantly increased in diabetic rats and was not changed
by quercetin. Streptozotocin administration induced significant increases in
hepatic TBARS concentration, QL, and SOD and catalase activities that were
prevented by quercetin. Activation of NF-κB, induction of IKKα and iNOS protein
levels, and increased degradation of IκBα were also observed in
streptozotocin-treated rats. All of those effects were abolished by quercetin.
These findings suggest that quercetin treatment, by abolishing the IKK/NF-κB
signal transduction pathway, may block the production of noxious mediators
involved in the development of early diabetes tissue injury and in the evolution
of late complications.
https://academic.oup.com/jn/article/135/10/2299/4669860