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首页> 外文期刊>Physiological Reports >Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice
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Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice

机译：二甲双胍在小鼠单侧输尿管梗阻期间调节肾脏的免疫细胞浸润

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Metformin is today the first choice treatment for type‐2 diabetes, but has also protective effects in several renal disease models. Previously, we have demonstrated that the protective effects in response to unilateral ureteral obstruction (UUO) are independent of organic cation transporters (OCTs), the transporters responsible for the metformin uptake into the renal cells. The mechanisms behind the renoprotective effects are incompletely understood, but our previous results indicate that the renoprotective effects at least partly could be dependent on actions of metformin outside the renal cells. In this study, we investigate whether the renoprotective effects of metformin can be mediated via systemic immunomodulatory actions. We demonstrated that metformin can affect the immune system in the kidney as well as in the peripheral blood and spleen following UUO. UUO kidneys showed infiltration of immune cells including monocytes, B cells, and T cells, but metformin limited infiltration of all cell types. UUO animals had increased spleen sizes, but this increase was attenuated by metformin. Metformin treatment surprisingly resulted in a higher proportion of monocytes with infiltratory capacity 7?days after UUO. Other studies have suggested that metformin regulates monocyte maturation through signal transducer and activator of transcription 3 (STAT3) activation, as also indicated by our results. In conclusion, our results demonstrate that metformin limits the infiltration of immune cells into the kidney, as well as modulates immune cell composition at a systemic level.
机译：二甲双胍今天是2型糖尿病的首选治疗，但在几种肾病模型中也具有保护作用。以前，我们已经证明，响应单侧输尿管阻塞（UUO）的保护效应与有机阳离子转运蛋白（OCT），负责二甲双胍的转运蛋白吸收到肾细胞中。无完全理解后矫正作用的机制，但我们以前的结果表明，至少部分地的再试反应效应可能依赖于肾细胞外部的二甲双胍的作用。在这项研究中，我们研究了二甲双胍的无重塑作用是否可以通过全身免疫调节作用介导。我们证明二甲双胍可以影响肾脏的免疫系统以及UUO后的外周血和脾脏。 UUO肾脏显示免疫细胞的浸润，包括单核细胞，B细胞和T细胞，但Metformin限制了所有细胞类型的渗透。 UUO动物增加了脾尺寸，但通过二甲双胍衰减这种增加。二甲双胍治疗令人惊讶地导致渗透能力的单核细胞比例较高7？UUO后的天数。其他研究表明，二甲双胍通过信号传感器和转录3（STAT3）活化的活化剂调节单核细胞成熟，如我们的结果表明。总之，我们的结果表明，二甲双胍将免疫细胞的渗透限制为肾脏，以及在全身水平下调节免疫细胞组合物。

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