Wei Xian, Wang Yuzhi, Weng Jiali, Lao Yunlan, Deng Ruyu, Lu Jiandong, Yang Shudong, Liu Xinhui
Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen 518000, China.
The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen 518000, Guangdong, China.
Evid Based Complement Alternat Med. 2022 May 21;2022:5812105. doi: 10.1155/2022/5812105. eCollection 2022.
Chronic kidney disease (CKD) is a major public health problem worldwide. Treatment with renin-angiotensin system inhibitors can achieve only partial efficacy on renal function decline and renal fibrosis in CKD patients. Huangqi-Danshen decoction (HDD) is a basic Chinese herbal pair which is commonly used to treat CKD with good efficacy.
The current study aimed to investigate the effect of perindopril erbumine (PE), an angiotensin-converting enzyme inhibitor, combined with HDD on adenine-induced CKD rat model and explore the possible mechanism from Sirtuin3/mitochondrial dynamics pathway.
CKD rat model was established by feeding of 0.75% w/w adenine containing diet for 3 weeks. At the same time, the treatment groups were given PE (0.42 mg/kg/d) or HDD (4.7 g/kg/d) or PE combined with HDD by gavage for 4 weeks. Renal function was evaluated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The renal pathological injury was observed by periodic acid-Schiff (PAS) and Masson's trichrome staining. Proteins expression was determined by Western blot analysis. Mitochondrial morphology was observed by transmission electron microscopy.
PE in combination with HDD significantly improved renal function, reduced tubular injury and interstitial fibrosis in adenine-induced CKD rats. Moreover, PE + HDD treatment mainly activated the Sirtuin3 expression level. In addition, PE + HDD exhibited bidirectional regulation on mitochondrial dynamics by suppressing mitochondrial fission protein dynaminrelated protein 1 expression and elevating mitochondrial fusion protein optic atrophy 1 expression, resulted in restraint of mitochondrial fragmentation.
The combination of PE and HDD attenuated adenine-induced CKD in rats, which was possibly associated with Sirtuin3/mitochondrial dynamics pathway.
慢性肾脏病（CKD）是全球主要的公共卫生问题。肾素 - 血管紧张素系统抑制剂治疗CKD患者时，在肾功能下降和肾纤维化方面仅能取得部分疗效。黄芪 - 丹参汤（HDD）是常用的治疗CKD的基础中药药对，疗效良好。
本研究旨在探讨血管紧张素转换酶抑制剂培哚普利叔丁胺盐（PE）联合HDD对腺嘌呤诱导的CKD大鼠模型的影响，并从沉默信息调节因子3/线粒体动力学途径探索其可能机制。
通过喂养含0.75%（w/w）腺嘌呤的饮食3周建立CKD大鼠模型。同时，治疗组通过灌胃给予PE（0.42mg/kg/d）或HDD（4.7g/kg/d）或PE联合HDD，持续4周。通过血清肌酐（Scr）和血尿素氮（BUN）水平评估肾功能。通过高碘酸 - 希夫（PAS）染色和Masson三色染色观察肾脏病理损伤。通过蛋白质印迹分析确定蛋白质表达。通过透射电子显微镜观察线粒体形态。
PE联合HDD可显著改善腺嘌呤诱导的CKD大鼠的肾功能，减轻肾小管损伤和间质纤维化。此外，PE + HDD治疗主要激活了沉默信息调节因子3的表达水平。此外，PE + HDD通过抑制线粒体分裂蛋白动力相关蛋白1的表达和提高线粒体融合蛋白视神经萎缩蛋白1的表达，对线粒体动力学表现出双向调节作用，从而抑制线粒体碎片化。
PE与HDD联合使用可减轻腺嘌呤诱导的大鼠CKD，这可能与沉默信息调节因子3/线粒体动力学途径有关。
