Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase Expression.
Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase Expression.
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中药消肾方通过抑制精氨酸酶激活和乙酰肝素酶表达改善糖尿病肾病肾小球过度滤过
DOI：
10.3389/fphys.2018.01195
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发表时间：
2018
影响因子：
4
通讯作者：
Yao L
中科院分区：
文献类型：
--
作者：
An X;Zhang M;Zhou S;Lu T;Chen Y;Yao L
高血糖会引起肾小球过度滤过，从而导致糖尿病肾病（DN）的发展，而这种疾病的治疗仍然是一个挑战。本研究探讨消肾方（XSF）治疗链脲佐菌素（STZ）诱导的1型DN小鼠模型肾损伤的作用及其在培养的人肾小球内皮细胞（hGECs）中的潜在机制。使用对照、糖尿病 DN、用 XSF 组（1 g/kg/d、LXSF 或 3 g/kg/d、HXSF）治疗 6 周的 DN 进行研究，并用高葡萄糖培养基中含有 HXSF (MS-HXSF) 和精氨酸酶抑制剂（ABH，100 μM）的小鼠血清对 hGEC 进行后处理。 HXSF 治疗恢复了 STZ 诱导的肾脏高滤过、肾小球硬化、肾微血管重塑以及全身活性氧化物质和炎症细胞因子水平的升高，同时防止肾小球硫酸肝素表达的降低以及皮质乙酰肝素酶和精氨酸酶2蛋白和精氨酸酶活性水平的升高。在 hGECs 研究中，MS-HXSF 改善了精氨酸酶活性、乙酰肝素酶蛋白/mRNA 表达、血管细胞粘附分子-1、细胞间粘附分子-1、单核细胞趋化蛋白-1 的 mRNA 水平和 hGECs 单层通透性的增强以及一氧化氮产生的抑制。除了所有这些保护作用外，XSF 还在体内和体外研究中减弱了 TNF-α 的 mRNA 表达，ABH 或 HXSF 加 ABH 的后处理没有改变这一点。本研究表明，XSF在DN模型中的保护作用可能与通过干预肾小球内皮精氨酸酶-乙酰肝素酶信号通路等多靶点的血管预防、抗炎和抗氧化有关。
Hyperglycemia induces glomerular hyper-filtration, which contributes to the development of diabetic nephropathy (DN), a condition that remains a challenge for treatment. The present study investigated the effect of Xiao-Shen-Formula (XSF) used for treatment of renal injury in type 1 DN mice model induced by streptozotocin (STZ) and its underlying mechanism in cultured human glomerular endothelial cell (hGECs). Studies were performed using control, diabetic DN, DN treated with XSF groups (1 g/kg/d, LXSF or 3 g/kg/d, HXSF) for 6 weeks and hGECs were post-treated with mice serum containing HXSF (MS-HXSF) and arginase inhibitor (ABH, 100 μM) in high glucose medium. HXSF treatment restored STZ-induced renal hyper-filtration, glomerulosclerosis, renal microvascular remodeling and the increased levels of systemic reactive oxidative species and inflammatory cytokines, accompanied by preventing the decreased expression of glomerular heparin sulfate and the increased levels of cortical heparanase and argianse2 protein and arginase activity. In hGECs study, MS-HXSF ameliorated the enhancement in arginase activity, the protein/mRNA expression of heparanase, mRNA levels of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and permeability of hGECs monolayers as well as the depression of nitric oxide production. Besides all these protective effects, XSF blunted the mRNA expression of TNF-α in vivo and vitro studies as well, which was not changed by the post-treatment of ABH or HXSF plus ABH. This study demonstrated that the protective effect of XSF might be related with vascular prevention, anti-inflammation and anti-oxidation through intervening multi-targets including glomerular endothelial arginase-heparanase signaling pathway in DN model.
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影响因子：
7.3
作者：
Romero MJ;Yao L;Sridhar S;Bhatta A;Dou H;Ramesh G;Brands MW;Pollock DM;Caldwell RB;Cederbaum SD;Head CA;Bagi Z;Lucas R;Caldwell RW
通讯作者：
Caldwell RW
影响因子：
--
作者：
Coca SG;Ismail-Beigi F;Haq N;Krumholz HM;Parikh CR
通讯作者：
Parikh CR
影响因子：
7.7
作者：
Okada, S;Shikata, K;Makino, H
通讯作者：
Makino, H
影响因子：
7.7
作者：
Maxhimer, JB;Somenek, M;Xu, XL
通讯作者：
Xu, XL
影响因子：
3.7
作者：
Garsen M;Rops AL;Li J;van Beneden K;van den Branden C;Berden JH;Rabelink TJ;van der Vlag J
通讯作者：
van der Vlag J