Effects of rikkunshito on renal fibrosis and inflammation in angiotensin II-infused mice
Effects of rikkunshito on renal fibrosis and inflammation in angiotensin II-infused mice
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DOI：
10.1038/s41598-019-42657-1
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发表时间：
2019-04-17
影响因子：
4.6
通讯作者：
Tamura, Kouichi
中科院分区：
文献类型：
--
作者：
Azushima, Kengo;Uneda, Kazushi;Tamura, Kouichi
慢性肾脏疾病的潜在发病机制涉及激活的肾素-血管紧张素系统和全身炎症，最终发展为肾损伤。Rikkunshito（RKT）通过增强ghrelin信号通路发挥抗纤维化和抗炎作用。本研究通过血管紧张素Ⅱ（Ang Ⅱ）诱导的肾损伤模型，观察RKT对肾纤维化和炎症的影响。Ang II灌注小鼠表现出高血压、心肌肥大、血尿素氮和血清肌酐升高、中度蛋白尿和肾脏病理改变，如轻度尿管型、间质巨噬细胞浸润和中度间质纤维化。RKT对Ang Ⅱ诱导的肾功能不全和肾纤维化无明显影响，但能减少肾间质巨噬细胞浸润。此外，RKT显着恢复血管紧张素II诱导的肾纤维化和炎症相关基因的表达，如3型胶原蛋白，转化生长因子β，单核细胞趋化蛋白-1和白细胞介素-6的变化。此外，虽然RKT不影响肾生长激素释放肽受体的表达，血管紧张素II诱导的肾sirtuin 1的表达减少，生长激素释放肽受体的关键下游途径，恢复RKT。这些结果表明，RKT在肾损伤的发展中可能具有肾脏抗炎作用，并且这种作用可能通过ghrelin信号通路介导。
The underlying pathogenesis of chronic kidney disease involves an activated renin-angiotensin system and systemic inflammation which ultimately develop renal injury. Rikkunshito (RKT) has been reported to exert anti-fibrotic and anti-inflammatory effects through enhancement of ghrelin signaling pathway. In this study, we investigated the effects of RKT on renal fibrosis and inflammation in angiotensin II (Ang II)-induced renal injury model. Ang II-infused mice exhibited hypertension, cardiac hypertrophy, increases in blood urea nitrogen and serum creatinine, moderate albuminuria and renal pathological changes such as mild urinary cast, interstitial macrophage infiltration and modest interstitial fibrosis. RKT had no evident effects on the Ang II-induced renal functional insufficiency and fibrosis, but attenuated renal interstitial macrophage infiltration. In addition, RKT significantly restored the Ang II-induced alteration in the expression of renal fibrosis- and inflammation-related genes such as type 3 collagen, transforming growth factor-beta, monocyte chemoattractant protein-1 and interleukin-6. Furthermore, although RKT did not affect the expression of renal ghrelin receptor, an Ang II-induced decrease in renal sirtuin 1 expression, a critical down-stream pathway of the ghrelin receptor, was restored by RKT. These findings suggest that RKT potentially has a renal anti-inflammatory effect in the development of renal injury, and this effect could be mediated by the ghrelin signaling pathway.