Panax notoginseng saponins protect kidney from diabetes by up-regulating silent information regulator 1 and activating antioxidant proteins in rats
Panax notoginseng saponins protect kidney from diabetes by up-regulating silent information regulator 1 and activating antioxidant proteins in rats
复制标题
三七皂苷通过上调沉默信息调节因子 1 并激活大鼠抗氧化蛋白来保护肾脏免受糖尿病
DOI：
10.1007/s11655-015-2446-1
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发表时间：
2016-12-01
影响因子：
2.9
通讯作者：
Chai Ke-fu
中科院分区：
文献类型：
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作者：
Du Yue-guang;Wang Li-pei;Chai Ke-fu
为探讨三七总皂苷(PNS)对糖尿病大鼠肾脏的保护作用机制，采用静脉注射四氧嘧啶复制糖尿病大鼠模型，随机分为模型组、PNS-100 mg/(kg·d)组和PNS-200 mg/(kg·d)组，每组10只。另取10只注射生理盐水的大鼠作为对照组。用高碘酸-席夫染色和免疫组织化学方法观察骨形态发生蛋白-7(BMP-7)的组织形态和组织表达。通过RNA干扰沉默大鼠肾小球系膜细胞沉默的信息调节因子1(SIRT1)。逆转录-聚合酶链式反应检测SIRT-1、单核细胞趋化蛋白-1(MCP-1)、转化生长因子-β1(TGF-β1)和纤溶酶原激活物抑制物-1(PAI-1)的mRNA表达。免疫印迹法检测SIRT1蛋白表达和核因子-kappaB(NF-kappa B)p65乙酰化水平。采用酶联免疫吸附试验检测细胞培养上清液中单核细胞趋化蛋白-1、转化生长因子-β1和丙二醛的浓度。采用经典的氮蓝四法测定超氧化物歧化酶活性。在糖尿病模型大鼠中，三七总皂甙不仅能降低血糖和血脂(P<；0.01)，而且能提高BMP-7的蛋白水平，抑制PAI-1的表达，从而抑制肾脏纤维化。在大鼠系膜细胞中，三七总皂甙可上调SIRT1的表达(P<0.01)，进而抑制转化生长因子-β1(P<；0.05)和单核细胞趋化蛋白-1(P<；0.05)的转录。三七总皂甙还可逆转高糖所致的NF-kappa B p65乙酰化水平的升高。此外，氧化还原调节因子丙二醛下调(P<；0.05)，超氧化物歧化酶上调(P<；0.01)，三七总皂甙可能通过上调SIRT1的表达，减少炎症细胞因子和转化生长因子-β1的诱生，激活抗氧化蛋白，从而抑制炎症反应，从而保护肾脏免受糖尿病的侵袭。
To explore the mechanism of the protective effects of Panax notoginseng saponins (PNS) on kidney in diabetic rats.Diabetic rat model was obtained by intravenous injection of alloxan, and the rats were divided into model, PNS-100 mg/(kg day) and PNS-200 mg/(kg day) groups, 10 each. Another 10 rats injected with saline were served as control. Periodic acid-Schiff staining and immunological histological chemistry were used to observe histomorphology and tissue expression of bone morphogenetic protein-7 (BMP-7). Silent information regulator 1 (SIRT1) was silenced in rat mesangial cells by RNA interference. The mRNA expressions of SIRT-1, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta 1 (TGF-beta 1) and plasminogen activator inhibitor-1 (PAI-1) were analyzed by reverse transcription polymerase chain reaction. The protein expressions of SIRT1 and the acetylation of nuclear factor kappa B (NF-kappa B) P65 were determined by western blotting. The concentration of MCP-1, TGF-beta 1 and malondialdehyde (MDA) in culture supernatant were detected by enzyme-linked immuno sorbent assay. The activity of superoxide dismutase (SOD) was detected by the classical method of nitrogen and blue four.In diabetic model rats, PNS could not only reduce blood glucose and lipid (P < 0.01), but also increase protein level of BMP-7 and inhibit PAI-1 expression for suppressing fibrosis of the kidney. In rat mesangial cells, PNS could up-regulate the expression of SIRT1 (P < 0.01) and in turn suppress the transcription of TGF-beta 1 (P < 0.05) and MCP-1 (P < 0.05). PNS could also reverse the increased acetylation of NF-kappa B p65 by high glucose. In addition, redox regulation factor MDA was down-regulated (P < 0.05) and SOD was up-regulated (P < 0.01), which were both induced by SIRT1 up-regulation.PNS could protect kidney from diabetes with the possible mechanism of up-regulating SIRT1, therefore inhibiting inflammation through decreasing the induction of inflammatory cytokines and TGF-beta 1, as well as activating antioxidant proteins.