Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
BMC Complement Altern Med. 2018 Dec 20;18(1):340. doi: 10.1186/s12906-018-2395-2.
Jian-Pi-Yi-Shen Formula (JPYSF), a Chinese herbal decoction with the efficacies of 'fortify the spleen and tonify the kidney' and 'activate blood and resolve stasis', is effective for the treatment of chronic kidney disease in clinic. However, the underlying mechanism remains unclear. The aim of this study was to investigate the therapeutic effects and possible mechanisms of JPYSF on retarding chronic kidney disease progression in 5/6 nephrectomized (5/6 Nx) rats.
Perindopril (4 mg/kg/d) and JPYSF (2.72 g/kg/d) were administrated by gavage to 5/6 Nx rats daily for 6 weeks. The therapeutic effects of JPYSF were evaluated by renal function, pathological injury, and fibrosis. The protein levels associated with mitochondrial quality control network were measured by Western blot and immunofluorescence analysis.
5/6 Nx rats showed obvious decline in renal function as evidenced by increased serum creatinine, blood urea nitrogen, and urinary protein excretion, and significant injury in kidney structure as evidenced by glomerular hypertrophy, tubular atrophy, and interstitial fibrosis. Administration of JPYSF for 6 weeks could improve renal function and ameliorate kidney structure injury in 5/6 Nx rats. Furthermore, the remnant kidneys of 5/6 Nx rats showed unbalanced mitochondrial quality control network manifested as decreased mitochondrial biogenesis, fusion, and mitophagy, and increased mitochondrial fission. Treatment of JPYSF could restore aforesaid aspects of mitochondrial quality control network.
These results indicate that JPYSF can notably ameliorate 5/6 Nx-induced chronic kidney disease, which may be related with modulation of mitochondrial quality control network.
健脾益肾方(JPYSF)是一种中药方剂,具有“健脾益肾”和“活血化瘀”的功效,在临床上对慢性肾脏病的治疗有效。然而,其潜在机制尚不清楚。本研究旨在探讨 JPYSF 对 5/6 肾切除(5/6 Nx)大鼠慢性肾脏病进展的治疗作用及可能机制。
普伐他汀(4mg/kg/d)和 JPYSF(2.72g/kg/d)灌胃给药,每天 1 次,连续 6 周。通过肾功能、病理损伤和纤维化评估 JPYSF 的治疗效果。通过 Western blot 和免疫荧光分析测量与线粒体质量控制网络相关的蛋白水平。
5/6 Nx 大鼠的肾功能明显下降,表现为血清肌酐、血尿素氮和尿蛋白排泄增加,肾脏结构损伤明显,表现为肾小球肥大、肾小管萎缩和间质纤维化。JPYSF 给药 6 周可改善 5/6 Nx 大鼠的肾功能和肾脏结构损伤。此外,5/6 Nx 大鼠的残余肾脏表现出失衡的线粒体质量控制网络,表现为线粒体生物发生、融合和自噬减少,以及线粒体分裂增加。JPYSF 治疗可恢复上述线粒体质量控制网络的各个方面。
这些结果表明,JPYSF 可显著改善 5/6 Nx 诱导的慢性肾脏病,这可能与调节线粒体质量控制网络有关。