目的：探究艾灸改善血管内皮功能的抗氧化效应机制。方法：将40只雄性SD大鼠随机分为空白组、模型组、艾灸组和eNOS抑制剂组，每组10只。采用高脂饲料喂养8周制备高脂血症大鼠模型。艾灸组予45 ℃艾灸“足三里”干预，10 min/次，eNOS抑制剂组在艾灸干预的同时予腹腔注射eNOS抑制剂，均1次/d，连续干预4周。采用HE染色法观察大鼠腹主动脉血管内皮形态；油红O脂肪染色法检测各组大鼠腹主动脉脂肪沉积情况；ELISA法检测血清及腹主动脉中血管活性物质及氧化应激相关指标水平；免疫荧光法检测大鼠腹主动脉中内皮型一氧化氮合酶(eNOS)的表达。结果：空白组腹主动脉呈粉红色，细胞核及血管周围组织结构清晰，血管内皮层光滑，血管内膜、中膜及外膜层纹理清晰；模型组腹主动脉呈暗粉色，颜色较淡，血管内皮层毛糙，血管内膜、中膜及外膜层纹理粗糙；艾灸组腹主动脉呈粉红色，细胞核及周围组织结构清晰，血管壁光滑；eNOS抑制剂组腹主动脉呈暗粉色，颜色较淡，纹理较粗糙。与空白组比较，模型组腹主动脉油红O染色面积比增大(P<0.05)；血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇（LDL-C）含量升高(P<0.01，P<0.05)，高密度脂蛋白胆固醇(HDL-C)含量降低(P<0.05)；血清及腹主动脉中内皮素-1(ET-1)含量升高(P<0.01，P<0.05)，一氧化氮(NO)、eNOS含量降低(P<0.05，P<0.001)；血清及腹主动脉中活性氧(ROS)、氧化型低密度脂蛋白(ox-LDL)、丙二醛(MDA)水平升高(P<0.001，P<0.01，P<0.000 1)，腹主动脉中超氧化物歧化酶(SOD)水平降低(P<0.000 1)；腹主动脉中eNOS荧光表达水平降低(P<0.05)。与模型组比较，艾灸组腹主动脉油红O染色面积比减小(P<0.05)；血清TC、TG、LDL-C含量降低(P<0.05)，HDL-C含量升高(P<0.05)；血清及腹主动脉中ET-1含量降低(P<0.01，P<0.05)，腹主动脉中NO、eNOS含量升高(P<0.001，P<0.01)；血清ROS、MDA水平降低(P<0.001，P<0.01)，腹主动脉中ROS、ox-LDL、MDA水平降低(P<0.05，P<0.01，P<0.001)，腹主动脉中SOD水平升高(P<0.000 1)；腹主动脉中eNOS荧光表达水平升高(P<0.05)。与艾灸组比较，eNOS抑制剂组血清TC、LDL-C、MDA水平升高(P<0.05)；腹主动脉中ET-1含量及ROS、ox-LDL、MDA水平升高(P<0.05), NO、eNOS含量及SOD水平降低(P<0.05);腹主动脉中eNOS荧光表达水平降低（P<0.05）。结论：45 ℃艾灸“足三里”可以保护和修复高脂血症大鼠腹主动脉的血管内皮损伤，改善血管内皮的氧化应激。.

2023-04-01·Pflügers Archiv - European Journal of Physiology

Ginkgolide B caused the activation of the Akt/eNOS pathway through the antioxidant effect of SOD1 in the diabetic aorta

Article

作者: Okudaira, Kanami ; Taguchi, Kumiko ; Matsumoto, Takayuki ; Kobayashi, Tsuneo

Ginkgo biloba extract (GBE) helps lower cardiovascular disease risk. Diabetes mellitus (DM)-induced endothelial dysfunction is a critical and initiating factor in the beginning of diabetic vascular complications. It was reported that GBE causes an endothelial-dependent relaxation. This study was designed to figure out the molecular basis on which GBE protects from endothelial dysfunction in diabetes because the underlying mechanisms are unclear. Studies were performed in a normal control group and streptozotocin/nicotinamide-induced DM group. In aortas, notably diabetic aortas, GBE, and ginkgolide B (GB), a constituent of GBE, produced a dose-dependent relaxation. The relaxation by GB was abolished by prior incubation with L-NNA (an endothelial nitric oxide synthase (NOS) inhibitor), LY294002 (a phosphoinositide 3-kinase (PI3K) inhibitor), and Akt inhibitor, confirming the essential role of PI3K/Akt/eNOS signaling pathway. We also demonstrated that GB induced the phosphorylation of Akt and eNOS in aortas. The superoxide dismutase1 (SOD1) expression level decreased in DM aortas, but GB stimulation increased SOD activity and SOD1 expression in DM aortas. Our novel findings suggest that in DM aortas, endothelial-dependent relaxation induced by GB was mediated by activation of SOD1, resulting in activation of the Akt/eNOS signaling pathway.

2021-11-01·Immunology3区 · 医学

Vascular and immunopathological role of Asymmetric Dimethylarginine (ADMA) in Experimental Autoimmune Encephalomyelitis

3区 · 医学

Article

作者: Islam, S. M. Touhidul ; Choi, Seungho ; Kim, Judong ; Won, Jeseong ; Singh, Inderjit ; Saxena, Nishant ; Khan, Mushfiquddin ; Singh, Avtar K.

SummaryAsymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor/uncoupler inducing vascular pathology. Vascular pathology is an important factor for the development and progression of CNS pathology of MS, yet the role of ADMA in MS remains elusive. Patients with multiple sclerosis (MS) are reported to have elevated blood levels of ADMA, and mice with experimental autoimmune encephalomyelitis (EAE, an animal model of MS) generated by auto‐immunization of myelin oligodendrocyte glycoprotein (MOG) and blood–brain barrier (BBB) disruption by pertussis toxin also had increased blood ADMA levels in parallel with induction of clinical disease. To explore the role of ADMA in EAE pathogenesis, EAE mice were treated with a daily dose of ADMA. It is of special interest that ADMA treatment enhanced the BBB disruption in EAE mice and exacerbated the clinical and CNS disease of EAE. ADMA treatment also induced the BBB disruption and EAE disease in MOG‐immunized mice even without pertussis toxin treatment, suggesting the role of ADMA in BBB dysfunction in EAE. T‐cell polarization studies also documented that ADMA treatment promotes TH1‐ and TH17‐mediated immune responses but without affecting Treg‐mediated immune response in EAE mice as well as in in vitro T‐cell culture. Taken together, these data, for the first time, document the vascular and immunopathogenic roles of ADMA in EAE, thus pointing to the potential of ADMA‐mediated mechanism as a new target of potential therapy for MS.

100 项与内皮型一氧化氮合酶（eNOS）基因疗法(Bayer AG) 相关的药物交易

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