Shen Shuai IIRecipe attenuates renal injury and fibrosis in chronic kidney disease by regulating NLRP3 inflammasome and Sirt1/Smad3 deacetylation pathway

BMC Complementary and Alternative Medicine

Liuyi Yang¹  Meng Wang¹  Jing Yang¹  Chen Wang² 

[1] 0000 0004 0604 8558, grid.412585.f, Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China;0000 0001 2372 7462, grid.412540.6, Key Laboratory of Liver and Kidney Diseases,Ministry of Education, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China;0000 0004 0604 8558, grid.412585.f, Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China;0000 0001 2372 7462, grid.412540.6, Key Laboratory of Liver and Kidney Diseases,Ministry of Education, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China;0000 0001 2372 7462, grid.412540.6, TCM institute of kidney disease, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China;0000 0001 2372 7462, grid.412540.6, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China;

关键词: Shen Shuai IIRecipe,Chronic kidney disease;    NLRP3 inflammasome;    Renal fibrosis;    Deacetylation;   

DOI  :  10.1186/s12906-019-2524-6

来源: publisher

【 摘 要 】

BackgroundExcessive activation of NLRP3 inflammasome and down-regulation of Sirt1/Smad3 deacetylation pathway play a significant role in the evolution of renal fibrosis. In China, it has been well known that Chinese herbal medicine is markedly effective in treating chronic kidney disease (CKD). Shen Shuai IIRecipe (SSR) has been used clinically for more than 20 years and has been confirmed to be effective in improvements of renal function and fibrosis. However, the specific mechanisms under the efficacy require further research. The purpose of this study was to evaluate whether SSR could alleviate renal injury and fibrosis by regulating NLRP3 inflammasome and Sirt1/Smad3 deacetylation pathway.MethodsFour weeks after 5/6 ablation/infarction (A/I) surgery, Sprague-Dawley rats were randomly divided into the following groups: sham operation group, 5/6 (A/I) group, 5/6 (A/I) + SSR group, and 5/6 (A/I) + Losartan group (5/6 (A/I) + Los). After 8 weeks intervention,we mainly assessed the severity of renal injury and fibrosis along with the activation of NLRP3 inflammasome and Sirt1/Smad3 deacetylation pathway.ResultsSSR significantly attenuated renal injury and fibrosis in the remnant kidneys. In addition, we found that SSR effectively inhibited activation of NLRP3/ASC/Caspase-1/IL-1βcascade, decreased inflammatory infiltration and up-regulated Sirt1/Smad3 deacetylation pathway.ConclusionsSSR could contribute to renal protection by inhibiting the activation of NLRP3 inflammasome and, furthermore, strengthen the antifibrotic effects by up-regulating Sirt1/Smad3 deacetylation pathway in 5/6 renal (A/I) model.

【 授权许可】

CC BY