Angiotensin(1-7) attenuates the progression of streptozotocin-induced diabetic renal injury better than angiotensin receptor blockade.
Angiotensin(1-7) attenuates the progression of streptozotocin-induced diabetic renal injury better than angiotensin receptor blockade.
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血管紧张素 (1-7) 比血管紧张素受体阻断更好地减轻链脲佐菌素诱导的糖尿病肾损伤的进展。
DOI：
10.1038/ki.2014.274
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发表时间：
2015-02
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
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作者：
为探讨Mas受体的内源性配体血管紧张素（1-7）（Ang（1-7））对链脲佐菌素（STZ）诱导的糖尿病肾病的治疗作用，将雄性Wistar大鼠随机分为对照组和糖尿病模型组。12周后，将糖尿病大鼠分为治疗4周的亚组，包括未治疗组、小、中、大剂量Ang（1-7）组、缬沙坦组、大剂量Ang（1-7）+缬沙坦组和A779（Mas受体拮抗剂）组，每组15只。Ang（1-7）可改善肾功能，减轻肾小球硬化、氧化应激和细胞增殖，降低IV型胶原、TGF-β1、VEGF、NOX 4、p47 phox、PKCα和PKCβ1的表达以及Smad 3的磷酸化。在大鼠系膜细胞系HBZY-1中，Ang（1-7）可降低高糖诱导的氧化应激，抑制细胞增殖，抑制NOX 4、p47 phox和TGF-β1的表达，抑制Smad 3、IV型胶原和VEGF的磷酸化，抑制PKCα和PKCβ1的膜转位。A779在体内和体外均能阻断Ang（1-7）的作用。大剂量Ang（1-7）单用及与缬沙坦联合应用的作用均上级缬沙坦单用，但与单独应用Ang（1-7）相比无明显协同作用。因此，Ang（1-7）改善链脲佐菌素诱导的糖尿病肾损伤。大剂量治疗在减轻氧化应激和抑制TGFβ1/Smad 3和VEGF介导的通路方面优于缬沙坦上级。
To explore the potential therapeutic effects of angiotensin(1–7) (Ang(1–7)), an endogenous ligand of the Mas receptor, on streptozotocin-induced diabetic nephropathy, male Wistar rats were randomly divided into two groups: a control group and a diabetic model group. After 12 weeks, the diabetic rats were divided into subgroups for 4-week treatments consisting of no-treatment group, small-, moderate-, and large-dose Ang(1–7) groups, a valsartan group, a large-dose Ang(1–7) plus valsartan group, and an A779 (antagonist of the Mas receptor) group, each with 15 rats. Ang(1–7) improved renal function, attenuated glomeruli sclerosis, oxidative stress, and cell proliferation, decreased the expression of collagen IV, TGF-β1, VEGF, NOX4, p47phox, PKCα, and PKCβ1, and the phosphorylation of Smad3. In the rat mesangial HBZY-1 cell line, Ang(1–7) decreased high-glucose-induced oxidative stress, the proliferation and expression of NOX4, p47phox, and TGF-β1, the phosphorylation of Smad3, collagen IV, and VEGF, and the membrane translocation of PKCα and PKCβ1. A779 blocked the effects of Ang(1–7) both in vivo and in vitro. The effects of large-dose Ang(1–7) alone and in combination with valsartan were superior to valsartan alone, but the combination had no significant synergistic effect compared with Ang(1–7) alone. Thus, Ang(1–7) ameliorated streptozotocin-induced diabetic renal injury. Large-dose treatment was superior to valsartan in reducing oxidative stress and inhibiting TGFβ1/Smad3- and VEGF-mediated pathways.
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影响因子：
5.7
作者：
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通讯作者：
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作者：
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DOI：
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发表时间：
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作者：
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作者：
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