Boldine Improves Kidney Damage in the Goldblatt 2K1C Model Avoiding the Increase in TGF-β.
Boldine Improves Kidney Damage in the Goldblatt 2K1C Model Avoiding the Increase in TGF-β.
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DOI：
10.3390/ijms19071864
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发表时间：
2018-06-25
影响因子：
5.6
通讯作者：
Velarde V
中科院分区：
文献类型：
--
作者：
Gómez GI;Velarde V
博尔丁是智利博尔多树中发现的一种主要的阿朴吗啡生物碱，是一种有效的抗氧化剂。氧化应激在肾血管性高血压(RVH)肾损害的发病机制中起着不利的作用。肾素-血管紧张素系统(RAS)的激活在高血压肾损害的发生发展中起着至关重要的作用，转化生长因子-β与RAS的激活密切相关。在本研究中，我们使用2K1C高血压模型评估了冰片碱对肾脏疾病进展的影响，并确定了RAS中的介质，如转化生长因子-β，可以被这种生物碱调节。根据这一假设，大鼠(n=5/组)在2K1C手术后(压力≥180毫米汞柱)给予冰片(50 mg/kg/d，灌胃)6周。肾功能评价采用尿蛋白/尿肌酸比值(U prot/U Crea)，氧化应激(OS)测定硫代巴比妥酸反应物质(TBARS)。每周追踪一次血压变化情况。α-平滑肌肌动蛋白(α-SMA)和Col III作为肾脏损害的标志物，ED-1和骨桥蛋白(OPN)作为炎症标志物。我们还探讨了血管紧张素转换酶-1和转化生长因子-β在RAS介质中的作用。博来丁治疗可降低2K1C高血压大鼠的UProt/UCrea比值、血浆总胆红素受体，并轻微降低SBP，而对对照组动物无影响。与2K1C大鼠相比，用冰片治疗的2K1C大鼠α-SMA、Col III、ED-1和OPN水平降低。博尔丁可阻止2K1C大鼠血管紧张素转换酶-1和转化生长因子-β的升高，提示博尔丁可减轻肾脏损伤。这些结果表明，冰片有可能被用作保健品。
Boldine, a major aporphine alkaloid found in the Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of kidney damage in renovascular hypertension (RVH). The activation of the renin-angiotensin system (RAS) is crucial to the development and progression of hypertensive renal damage and TGF-β is closely associated with the activation of RAS. In the present study, we assessed the effect of boldine on the progression of kidney disease using the 2K1C hypertension model and identifying mediators in the RAS, such as TGF-β, that could be modulated by this alkaloid. Toward this hypothesis, rats (n = 5/group) were treated with boldine (50 mg/kg/day, gavage) for six weeks after 2K1C surgery (pressure ≥ 180 mmHg). Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive substances (TBARS). The evolution of systolic blood pressure (SBP) was followed weekly. Alpha-smooth muscle actin (α-SMA) and Col III were used as markers of kidney damage; ED-1 and osteopontin (OPN) were used as markers of inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF-β. Boldine treatment reduced the UProt/UCrea ratio, plasma TBARS, and slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED-1, and OPN were lower when compared to 2K1C rats. Boldine prevented the increase in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney damage. These results suggest that boldine could potentially be used as a nutraceutic.
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影响因子：
7.2
作者：
Fernandez, J.;Lagos, P.;Zamorano-Ponce, E.
通讯作者：
Zamorano-Ponce, E.
影响因子：
8.3
作者：
Border, WA;Noble, NA
通讯作者：
Noble, NA
影响因子：
8.3
作者：
GUAN, S;FOX, J;NAVAR, LG
通讯作者：
NAVAR, LG
影响因子：
3.2
作者：
LOPEZDELEON, A;ROJKIND, M
通讯作者：
ROJKIND, M
影响因子：
--
作者：
Forni, Cinzia;Braglia, Roberto;Beninati, Simone
通讯作者：
Beninati, Simone