Aging is a multifactorial process involving the cumulative effects of inflammation, oxidative stress, and mitochondrial dynamics, which can produce complex structural and biochemical alterations to the nervous system and lead to dysfunction of microcirculation, blood-brain barrier (BBB), and other problems in the brain. Long-term injection of D-galactose (D-gal) can induce chronic inflammation and oxidative stress, accelerating aging. The model of accelerated aging with long-term administration of D-gal have been widely used in anti-aging studies, due to the increase of chronic inflammation and decline of cognition that similarity with natural aging in animals. However, despite extensive researches in the D-gal-induced aging rats, studies on their microvasculature remain limited. Endothelial progenitor cells (EPCs), which are precursors to endothelial cells (ECs), play a significant role in the repair and regeneration process of endogenous blood vessel, and adiponectin (APN), a protein derived from adipocyte, has many effects on protective vascular endothelium and anti-inflammatory. Recently, many studies have shown that APN can promote improvements in cognitive function. Under these circumstances, we investigated the neuroprotective effect of the APN-transfected EPC (APN-EPC) treatment on rats after administration with D-gal and explored the likely underlying mechanisms. Compared to model group for D-gal administration, better cognitive function and denser microvessels were significantly found in the APN-EPC treatment group, and indicated APN-EPC treatment in aging rats could improve the cognitive dysfunction and microvessel density. The level of proinflammatory cytokines IL-1β, IL-6, and TNF-α, activated astrocytes and apoptosis rate were significantly reduced in the APN-EPC group compared with the model group, showed that APN-EPCs alleviated the neuroinflammation in aging rats. In addition, the APN-EPC group inhibited the decrease of BBB-related proteins claudin-5, occludin, and Zo-1 in aging rats and attenuated BBB dysfunction significantly. These results of our study indicated that APN-EPC treatment in D-gal-induced aging rats have a positive effect on improving cognitive and BBB dysfunction, increasing angiogenesis, and reducing neuroinflammation and apoptosis rate. This research suggests that cell therapy via gene modification may provide a safe and effective approach for the treatment of age-related neurogenerative diseases.

中文翻译：

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脂联素转染的内皮祖细胞对D-半乳糖诱导的衰老大鼠认知功能的保护作用。

衰老是一个多因素的过程，涉及炎症，氧化应激和线粒体动力学的累积效应，会导致神经系统发生复杂的结构和生化改变，并导致微循环功能障碍，血脑屏障（BBB）和其他疾病。大脑。长期注射D-半乳糖（D-gal）会引起慢性炎症和氧化应激，加速衰老。长期服用D-gal加速衰老的模型已被广泛用于抗衰老研究，这是由于慢性炎症的增加以及与动物自然衰老相似性的认知下降。然而，尽管在D-gal诱导的衰老大鼠中进行了广泛的研究，但是关于其微脉管系统的研究仍然有限。内皮祖细胞（EPC）它们是内皮细胞（EC）的前体，在内源性血管的修复和再生过程中起着重要作用，而脂联素（APN）是一种来自脂肪细胞的蛋白质，对保护性血管内皮和抗炎性具有许多作用。最近，许多研究表明APN可以促进认知功能的改善。在这种情况下，我们研究了DPN gal给药后APN转染的EPC（APN-EPC）处理对大鼠的神经保护作用，并探讨了可能的潜在机制。与D-gal给药模型组相比，APN-EPC治疗组的认知功能明显增强，且微血管密度更高，这表明APN-EPC治疗老年大鼠可改善认知功能障碍和微血管密度。与模型组相比，APN-EPC组的β，IL-6和TNF- α，活化的星形胶质细胞和凋亡率均明显降低，表明APN-EPCs减轻了衰老大鼠的神经炎症。此外，APN-EPC组抑制衰老大鼠BBB相关蛋白claudin-5，occludin和Zo-1的减少，并显着减轻BBB功能障碍。我们的研究结果表明，APN-EPC治疗D-gal引起的衰老大鼠对改善认知和BBB功能障碍，增加血管生成，降低神经炎症和凋亡率具有积极作用。这项研究表明，通过基因修饰的细胞疗法可能为治疗与年龄有关的神经生成性疾病提供一种安全有效的方法。