Jian-Pi-Yi-Shen formula enhances perindopril inhibition of chronic kidney disease progression by activation of SIRT3, modulation of mitochondrial dynamics, and antioxidant effects.
Jian-Pi-Yi-Shen formula enhances perindopril inhibition of chronic kidney disease progression by activation of SIRT3, modulation of mitochondrial dynamics, and antioxidant effects.
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健脾益肾方通过激活SIRT3、调节线粒体动力学及发挥抗氧化作用，增强培哚普利对慢性肾脏病进展的抑制作用。
DOI：
10.1042/bsr20211598
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发表时间：
2021-10-29
影响因子：
4
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Liu X;Deng R;Wei X;Wang Y;Weng J;Lao Y;Lu J;Xiong G;Li S
慢性肾脏病（CKD）是一个全球性的公共卫生问题。肾素-血管紧张素系统（RAS）阻断是CKD治疗的主要方法，但有局限性。健脾益肾方是一种传统的中药汤剂，几十年来一直用于治疗CKD。本研究旨在探讨培哚普利特丁胺（PE）联合健脾益肾方对慢性肾脏病（CKD）进展的干预作用及其机制。通过喂食含有0.75%w/w腺嘌呤的饮食3周来诱导CKD大鼠模型。CKD大鼠从诱导CKD开始，分别给予PE、JPYSF或PE+JPYSF治疗，持续4周。以血肌酐（Scr）、血尿素氮（BUN）为指标评价肾功能。病理学检查采用PAS染色和Masson三色染色。Western blot和免疫组化检测蛋白表达。透射电镜观察线粒体形态。结果表明，健脾益肾方联合PE能更好地改善CKD大鼠的肾功能和病理改变，减轻肾纤维化。PE和JPYSF的管理增强sirtuin 3（SIRT 3）的表达，抑制线粒体分裂，促进线粒体融合，并抑制CKD大鼠肾脏中的氧化应激。总之，联合使用PE和JPYSF比单独使用更有效地预防CKD。其潜在机制可能与SIRT 3的激活、线粒体动力学的调节和抗氧化作用有关。
Chronic kidney disease (CKD) is a global public health problem. Renin–angiotensin system (RAS) blockade is the mainstay of CKD therapy with limitations. Jian-Pi-Yi-Shen formula (JPYSF) is a traditional herbal decoction and has been used for treating CKD for decades. The purpose of the present study was to investigate the intervention effects of combined used of perindopril erbumine (PE) and JPYSF on CKD progression and explore their underlying mechanisms. CKD rat model was induced by feeding a diet containing 0.75% w/w adenine for 3 weeks. CKD rats were treated with PE or JPYSF or PE+JPYSF from the induction of CKD and lasted 4 weeks. Renal function was evaluated by serum creatinine (Scr) and blood urea nitrogen (BUN). Pathological lesions were observed by Periodic acid–Schiff (PAS) and Masson’s trichrome staining. The protein expression was tested by Western blot and immunohistochemistry analysis. The morphology of mitochondria was observed by transmission electron microscope. The results showed that combined used of PE and JPYSF could better improve renal function and pathological lesions and ameliorate renal fibrosis in CKD rats. Administration of PE and JPYSF enhanced sirtuin 3 (SIRT3) expression, inhibited mitochondrial fission, promoted mitochondrial fusion, and suppressed oxidative stress in the kidney of CKD rats. In conclusion, combined use of PE and JPYSF protected against CKD more effectively than either alone. The underlying mechanism may be associated with activation of SIRT3, modulation of mitochondrial dynamics, and antioxidant effects.