Scutellarin attenuates hypertension-induced expression of brain Toll-like receptor 4/nuclear factor kappa B.

Scutellarin attenuates hypertension-induced expression of brain Toll-like receptor 4/nuclear factor kappa B.
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DOI:
10.1155/2013/432623
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发表时间:
2013
影响因子:
4.6
通讯作者:
Huang R
Huang R
中科院分区:
医学3区
文献类型:
--
作者:
Chen X;Shi X;Zhang X;Lei H;Long S;Su H;Pei Z;Huang R

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高血压与低度炎症有关,toll样受体4 (TLR4)已被证明与高血压的发生和维持有关。本研究旨在探讨黄芩苷(每日灌胃2周)对肾血管性高血压大鼠TLR4/核因子κB- (NF-κB-)介导的脑炎症和血压的影响(采用2肾2夹法)。免疫荧光和western免疫印迹分析显示,高血压导致TLR4和NF-κB的激活,同时促炎介质如肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)和白细胞介素-18 (IL-18)的表达显著增加。此外,抗凋亡蛋白髓样细胞白血病-1 (Mcl1)的表达减少,促凋亡蛋白Bax和cleedcaspase - 3p17在大脑皮质/纹状体可溶性溶物中表达增加。黄芩苷能显著降低高血压大鼠血压,减少脑内活化的小胶质细胞和巨噬细胞数量。此外,黄芩素显著降低TLR4、NF-κB p65、TNF-α、IL-1β、IL-18、Bax和cleaved-caspase- 3p17的表达,增加Mcl1的表达。综上所述,黄芩苷具有抗炎、抗细胞凋亡和降低高血压大鼠血压的作用。因此,黄芩苷可能是一种潜在的治疗高血压相关疾病的药物。
Hypertension is associated with low-grade inflammation, and Toll-like receptor 4 (TLR4) has been shown to be linked to the development and maintenance of hypertension. This study aimed to investigate the effects of scutellarin (administered by oral gavage daily for 2 weeks) on brain TLR4/nuclear factor kappa B-(NF-κB-) mediated inflammation and blood pressure in renovascular hypertensive (using the 2-kidney, 2-clip method) rats. Immunofluorescence and western immunoblot analyses revealed that hypertension contributed to the activation of TLR4 and NF-κB, accompanied by significantly enhanced expression of proinflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18). Furthermore, expression of the antiapoptotic protein, myeloid cell leukemia-1 (Mcl1), was decreased, and the pro-apoptotic proteins, Bax and cleavedcaspase-3 p17 were increased in combined cerebral cortical/striatal soluble lysates. Scutellarin significantly lowered blood pressure and attenuated the number of activated microglia and macrophages in brains of hypertensive rats. Furthermore, scutellarin significantly reduced the expression of TLR4, NF-κB p65, TNF-α, IL-1β, IL-18, Bax and cleaved-caspase-3 p17, and increased the expression of Mcl1. Overall, these results revealed that scutellarin exhibits anti-inflammatory and anti-apoptotic properties and decreases blood pressure in hypertensive rats. Therefore, scutellarin may be a potential therapeutic agent in hypertension-associated diseases.
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