Targeting oxidative stress and new therapy in metabolic syndrome

在本研究中，我们研究了代谢综合征的新治疗方法。我们关注盐、醛固酮、炎症和肾上腺髓质素在氧化应激中的作用，并寻求新的靶点来降低氧化应激，从而保护器官免受损伤。此外，我们还研究了在代谢模型大鼠中诱导器官再生和新基因的可能治疗方法。我们发现，口服负荷盐增加ROS和增强胰岛素抵抗和心脏功能。肾上腺髓质素是一种内源性抗氧化剂，其缺乏可导致代谢综合征。Mac-1表达于白细胞表面，在白细胞粘附和血管损伤中起重要作用。利用局部Shwartzman反应模型，我们揭示了Mac-1在血管炎中的作用以及在预防代谢综合征中血管损伤的可能治疗靶点，其中局部血管炎症可能是发病机制之一。诱导器官再生 ...更多信息 作为一种有前途的治疗工具，在肾脏损伤中，我们将重点放在侧群细胞作为肾脏中的多能干细胞。使用几种肾损伤模型，我们发现，细胞因子诱导侧群细胞凋亡和抑制器官再生。醛固酮阻断、血管紧张素II阻断以及阿司他丁A的表观遗传学调节可以拯救受损肾脏中的侧群细胞。最后，我们对代谢综合征模型大鼠的可能遗传位点进行了研究，在3号、4号和12号染色体上发现了代谢综合征的致病基因。其中，犬尿氨酸转氨酶-1的突变在大鼠模型中将体重、血压、NEFA合成和胰岛素抵抗联系起来。总之，本研究为代谢综合征的治疗靶点提供了新的思路。氧化应激和醛固酮的重要性以及表观遗传学调控和新基因在代谢综合征的发病机制及相关器官损害中起着关键作用。现在有几种可能的化合物可以使我们进入治疗代谢综合征的新时代。少

In the present study, we have investigated new therapeutic approaches to metabolic syndrome. We have focused on the role of salt, aldosterone, inflammation, and adrenomedullin in relation to oxidative stress and seek new targets to reduce oxidative stress and thus protect organs from damages. In addition, we investigated possible therapeutic approaches to induce organ regenerations and new genes in metabolic model rats. We revealed that orally loaded salt increases ROS and aggravates insulin resistance, and cardiac function. Adrenomedullin has been reported as an intrinsic antioxidants and its deficiency induces metabolic syndrome. Mac-1 is expressed on leukocyte and plays an important role in leukocyte adherence and vascular damages. Using Local Shwartzman Reaction model, we revealed role of Mac-1 in vasculitis and possible therapeutic target in preventing vascular damages in metabolic syndrome where local vascular inflammation could be one pathogenesis. To induce organ regeneration i … More s a promising therapeutic tool and in renal damages, we focused on side population cell as a multipotent stem cells in the kidney. Using several renal impairment models, we revealed that cytokines induce side population cell apoptosis and suppresses organ regeneration. Aldosterone blockade, angiotensin II blockade as well as epigenetical regulation by trichostatin A could rescue side population cells in damaged kidney. Finally we investigated possible genetical locus in metabolic syndrome model rat and found responsible locus on chromosome 3, 4 and 12. Among them, mutation in kynurenine aminotransferase-1 links body weight, blood pressure, NEFA synthesis and insulin resistance in rat model. In conclusion, the present research project revealed several new insights in therapeutic target in metabolic syndrome. The importance of oxidative stress and aldosterone as well as epigenetical regulations and new gene are all play pivotal role in pathogenesis of metabolic syndrome and related organ damages. There are several possible compounds are now available that lead us to a new era in treating metabolic syndrome. Less