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Circulation:研究发现抑制血管内皮细胞炎症有助延寿

来源:新华网 2012-03-13 15:18

近日,国际著名学术杂志《循环》Circulation上刊登了日本东北大学一个研究小组的最新研究成果“Blockade of the NF-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Lifespans ”,文章中,研究者表示抑制血管内皮细胞炎症有助于延长寿命。

血管内皮细胞是血管最内侧一层薄薄的上皮细胞,它形成血管的内壁,直接与血液接触。日本一个研究小组在动物实验中发现,抑制内皮细胞的炎症,可以延缓机体衰老、延长寿命近三成。

研究人员表示,他们通过改造小鼠的基因,培育出血管内皮细胞不容易发生炎症的小鼠。结果发现,这种小鼠的血管老化受到遏制,小鼠变得更加活跃,而且血液循环更加顺畅,被认为可能导致衰老的活性氧的量减少三分之一左右。

这种小鼠的平均寿命较普通小鼠延长了约30%。如果以日本人的寿命换算,相当于平均寿命从83岁延长到108岁。研究人员认为,其原因可能在于血管内皮细胞的炎症对于动脉硬化症的发病等有重要影响,抑制炎症就可以保持血管的健康,延长寿命。

研究小组成员、东北大学教授片桐秀树指出,遏制血管的炎症,不仅能够防止患病的小鼠病情恶化,还能够在健康状态下进一步延长寿命。这一成果将有助于人类对抗衰老。(生物谷Bioon.com)

Blockade of the NF-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Lifespans

Yutaka Hasegawa1; Tokuo Saito1; Takehide Ogihara1; Yasushi Ishigaki1; Tetsuya Yamada1; Junta Imai1; Kenji Uno1; Junhong Gao1; Keizo Kaneko1; Tatsuo Shimosawa2; Tomoichiro Asano3; Toshiro Fujita2; Yoshitomo Oka1; Hideki Katagiri1*

Background—Nuclear factor-kappa B (NF-κB) signaling plays critical roles in physiological and pathological processes, such as responses to inflammation and oxidative stress.

Methods and Results—To examine the role of endothelial NF-κB signaling in vivo, we generated transgenic mice expressing dominant-negative IκB under the Tie2 promoter/enhancer (E-DNIκB mice). These mice exhibited functional inhibition of NF-κB signaling specifically in endothelial cells. Although E-DNIκB mice displayed no overt phenotypic changes when young and lean, they were protected from the development of insulin resistance associated with obesity, whether diet- or genetically-induced. Obesity-induced macrophage infiltration into adipose tissue and plasma oxidative stress markers were decreased, while blood flow and mitochondrial contents in muscle and active-phase locomotor activity were increased in E-DNIκB mice. In addition to inhibition of obesity-related metabolic deteriorations, blockade of endothelial NF-κB signaling prevented age-related insulin resistance and vascular senescence and, notably, prolonged lifespan. These anti-aging phenotypes were also associated with decreased oxidative stress markers, increased muscle blood flow, enhanced active-phase locomotor activity and aortic up-regulations of mitochondrial sirtuin-related proteins.

Conclusions—The endothelium plays important roles in obesity- and age-related disorders through intracellular NF-κB signaling, thereby, ultimately, impacting lifespan. Endothelial NF-κB signaling is a potential target for treating the metabolic syndrome as well as for anti-aging strategies.

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