Chaihuang Yishen Granules Improves Renal Fibrosis in Mice with Chronic Kidney Disease by Inhibiting Macrophagic Mincle
10.19378/j.issn.1003-9783.2023.12.002
- VernacularTitle:柴黄益肾颗粒抑制巨噬细胞Mincle改善小鼠慢性肾病模型肾纤维化
- Author:
Ruizhi TAN
1
;
Yuanxia ZOU
;
Peng LIU
;
Hongwei SU
;
Ping LI
;
Li WANG
Author Information
1. 西南医科大学附属中医医院中西医结合研究中心,四川 泸州 646000
- Keywords:
Chaihuang Yishen Granules;
macrophages;
Mincle;
unilateral ureteral obstruction(UUO);
chronic kidney disease;
renal fibrosis;
mice
- From:
Traditional Chinese Drug Research & Clinical Pharmacology
2023;34(12):1658-1667
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect and potential mechanism of Chaihuang Yishen Granules on renal fibrosis in mice with chronic kidney disease.Methods Thirty-six C57BL/6 male mice were randomly divided into sham group,model group,low-,and high-dose Chaihuang Yishen Granules groups(3.835 g·kg-1 and 7.67 g·kg-1),positive control group and Mincle ligand trehalose-6,6-dibehenate(TDB 10 mg·kg-1)group.Unilateral ureteral obstruction(UUO)was used to establish the model of renal fibrosis in mice.One hour after operation,mice in each drug-treated group were given corresponding drugs by gavage,and sham operation group and model group were given saline by gavage,once a day for 7 consecutive days.The pathological changes and fibrosis in the kidneys of mice in all groups were observed by hematoxylin eosin staining and Sirius red staining.The expressions and secretions of inflammatory factor IL-1β,IL-6 and TNF-α in kidneys of all groups were detected by Real-time PCR and ELISA.Immunohistochemistry and Western Blot were used to detect fibrosis indicators,including α-SMA and Fn protein levels.Immunofluorescence and Western Blot were further used to determine protein levels of Mincle and its downstream signal Syk/NF-κB.The proportion of Mincle positive macrophages was analyzed by flow cytometry.Results Compared with the model group,low-and high-dose Chaihuang Yishen Granules can effectively improve UUO-induced renal injury and fibrosis,and inhibit α-SMA and Fn protein levels in the kidney(P＜0.01).Moreover,high-dose Chaihuang Yishen Granules can effectively reduce the expressions and secretions of inflammatory factor IL-1β,IL-6 and TNF-α of kidney in UUO model(P＜0.01),as well as inhibit phosphorylation of NF-κB(P＜0.01).The mechanism study showed that Chaihuang Yishen Granules could significantly reduce the protein level of Mincle and the activity of its downstream signal Syk in the kidney of UUO mice(P＜0.01).After TDB was used to activate Mincle,the effect of Chaihuang Yishen Granules on improving renal injury,inflammatory factor secretion and fibrosis was significantly reduced(P＜0.05,P＜0.01).Conclusion Chaihuang Yishen Granules can improve UUO-induced renal injury,inflammation and fibrosis,and its mechanism may be related to the down-regulation of Mincle/Syk/NF-κB signaling pathway.
