导读：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。
日本东北大学的这个研究小组在新一期学术杂志《循环》上报告说，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。
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.
文献链接：https://circ.ahajournals.org/content/early/2012/02/01/CIRCULATIONAHA.111.054346.abstract
