Puerarin Alleviates UUO-Induced Inflammation and Fibrosis by Regulating the NF-κB P65/STAT3 and TGFβ1/Smads Signaling Pathways.
Puerarin Alleviates UUO-Induced Inflammation and Fibrosis by Regulating the NF-κB P65/STAT3 and TGFβ1/Smads Signaling Pathways.
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葛根素通过调节 NF-κB P65/STAT3 和 TGFβ1/Smads 信号通路减轻 UUO 引起的炎症和纤维化
DOI：
10.2147/dddt.s321879
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Sun L
中科院分区：
文献类型：
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作者：
Wang J;Ge S;Wang Y;Liu Y;Qiu L;Li J;Huang X;Sun L
葛根素（PR）是一种富含天然成分的中药，据报道具有抗纤维化、抗氧化、抗炎和免疫调节特性。然而，PR 对单侧输尿管梗阻（UUO）介导的肾损伤的保护机制尚未完全阐明。因此，本研究的目的是探讨PR对UUO小鼠的影响及其可能的机制。 C57BL/6小鼠32只，随机分为4组（n=8）：i）假手术组（Sham）； ii) UUO 集团（UUO）； iii) UUO + PR 50 毫克/公斤/天 (UUO + PRL)； iv) UUO + PR 100 mg/kg/天（UUO + PRH）。术后1周开始连续灌胃给药14天，Sham组和UUO组小鼠以相同方式给予等量载体。然后处死所有小鼠并收集血清、24小时尿液和组织标本用于肾功能、组织病理学、Western印迹、免疫组化。肾功能和组织病理学显示，PR 改善了 UUO 介导的肾功能障碍，并部分逆转了肾小管损伤和肾小管间质纤维化。此外，根据Western blot和免疫组化结果，PR抑制IL-1β、IL-6、MCP-1等炎症因子以及α-SMA、COL I和VIM等ECM相关蛋白的表达。更重要的是，PR治疗下纤维化通路TGF-β1、Smad3、p-Smad3和炎症通路NF-κB p65、NF-κB p-p65、STAT3、p-STAT3的表达均受到不同程度的抑制，而Smad7表达上调。这些发现表明，PR可能通过调节NF-κB p65/STAT3和TGFβ1/Smads通路来抑制炎症因子的募集和细胞外基质（ECM）沉积，从而减轻UUO诱导的炎症和纤维化反应，从而逆转肾损伤。
Puerarin (PR), a Chinese medicine rich in natural components, has been reported to display anti-fibrotic, antioxidant, anti-inflammatory and immunomodulatory properties. However, the protective mechanism of PR against unilateral ureteral obstruction (UUO)-mediated renal injury is not fully clarified. Therefore, the aim of this study was to investigate the effects of PR on UUO mice and its possible mechanisms. A total of 32 C57BL/6 mice were divided randomly into four groups (n=8): i) sham-operated group (Sham); ii) UUO group (UUO); iii) UUO + PR 50 mg/kg/day (UUO + PRL); and iv) UUO + PR 100 mg/kg/day (UUO + PRH). Continuous gavage administration for 14 days starting one week postoperatively, while the mice in Sham and UUO groups were given equal amounts of vehicle by the same means. All mice were then sacrificed and serum, 24-hour urine and tissue specimens were collected for renal function, histopathology, Western blot, immunohistochemistry. Renal function and histopathology revealed that PR improved UUO-mediated renal dysfunction and partially reversed tubular injury and tubulointerstitial fibrosis. Additionally, according to the results of Western blot and immunohistochemistry, PR inhibited the expression of inflammatory factors including IL-1β, IL-6, MCP-1 and ECM-related proteins including α-SMA, COL I and VIM. More importantly, the expression of fibrotic pathways TGF-β1, Smad3, p-Smad3 and inflammatory pathways NF-κB p65, NF-κB p-p65, STAT3, p-STAT3 were inhibited to various extents under the PR treatment, while Smad7 was upregulated. These findings indicate that PR may inhibit the recruitment of inflammatory factors and extracellular matrix (ECM) deposition through the regulation of the NF-κB p65/STAT3 and TGFβ1/Smads pathways, which alleviates the UUO-induced inflammatory and fibrotic response, thereby reversing renal injury.