血管內(nèi)皮細(xì)胞是血管最內(nèi)側(cè)一層薄薄的上皮細(xì)胞,，它形成血管的內(nèi)壁,，直接與血液接觸。
近日,，日本東北大學(xué)的一個(gè)研究小組在新一期學(xué)術(shù)雜志《循環(huán)》（Circulation）上報(bào)告說,，他們通過改造小鼠的基因，培育出血管內(nèi)皮細(xì)胞不容易發(fā)生炎癥的小鼠,。結(jié)果發(fā)現(xiàn),，這種小鼠的血管老化受到遏制，小鼠變得更加活躍,，而且血液循環(huán)更加順暢,，被認(rèn)為可能導(dǎo)致衰老的活性氧的量減少三分之一左右。
這種小鼠的平均壽命較普通小鼠延長了約30%,。如果以日本人的壽命換算,，相當(dāng)于平均壽命從83歲延長到108歲。研究人員認(rèn)為,，其原因可能在于血管內(nèi)皮細(xì)胞的炎癥對于動脈硬化癥的發(fā)病等有重要影響,，抑制炎癥就可以保持血管的健康，延長壽命,。
研究小組成員,、東北大學(xué)教授片桐秀樹指出，遏制血管的炎癥,，不僅能夠防止患病的小鼠病情惡化,，還能夠在健康狀態(tài)下進(jìn)一步延長壽命。這一成果將有助于人類對抗衰老,。（生物谷Bioon.com）
doi: 10.1161/?CIRCULATIONAHA.111.054346
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Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans
Yutaka Hasegawa, MD, PhD*; Tokuo Saito, MD, PhD*; Takehide Ogihara, MD, PhD; Yasushi Ishigaki, MD, PhD; Tetsuya Yamada, MD, PhD; Junta Imai, MD, PhD; Kenji Uno, MD, PhD; Junhong Gao, MD, PhD; Keizo Kaneko, MD, PhD; Tatsuo Shimosawa, MD, PhD; Tomoichiro Asano, MD, PhD; Toshiro Fujita, MD, PhD; Yoshitomo Oka, MD, PhD; Hideki Katagiri, MD, PhD
Background—Nuclear factor-κB (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 genetics-induced. Obesity-induced macrophage infiltration into adipose tissue and plasma oxidative stress markers were decreased and blood flow and mitochondrial content 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 life span. These antiaging phenotypes were also associated with decreased oxidative stress markers, increased muscle blood flow, enhanced active-phase locomotor activity, and aortic upregulation of mitochondrial sirtuin-related proteins.
Conclusions—The endothelium plays important roles in obesity- and age-related disorders through intracellular NF-κB signaling, thereby ultimately affecting life span. Endothelial NF-κB signaling is a potential target for treating the metabolic syndrome and for antiaging strategies.
