Regulatory effect of Traditional Chinese Medicinal Formula Zuo-Gui-Wan on the Th17/Treg paradigm in mice with bone loss induced by estrogen deficiency

被引:34
作者
Lai, Nannan [1 ,2 ,3 ,4 ]
Zhang, Zhirong [5 ]
Wang, Bin [6 ]
Miao, Xiuming [6 ]
Guo, Yuqi [1 ,2 ,3 ,4 ]
Yao, Chengfang [1 ,2 ,3 ,4 ]
Wang, Zhaoxia [1 ,2 ,3 ,4 ]
Wang, Li [1 ,2 ,3 ,4 ]
Ma, Ruiping [7 ]
Li, Xia [1 ,2 ,3 ]
Jiang, Guosheng [1 ,2 ,3 ]
机构
[1] Shandong Acad Med Sci, Inst Basic Med, Key Lab Tumor Immunol & Tradit Chinese Med Immuno, Jinan 250062, Peoples R China
[2] Shandong Acad Med Sci, Inst Basic Med, Key Lab Rare & Uncommon Dis, Jinan 250062, Peoples R China
[3] Shandong Acad Med Sci, Inst Basic Med, Minist Publ Hlth, Key Lab Biotechnol Drugs, Jinan 250062, Peoples R China
[4] Shandong Acad Med Sci, Inst Basic Med, Lab Immunopharmacol State Adm Tradit Chinese Med, Jinan 250062, Peoples R China
[5] Shandong Univ, Yantai Yuhuangding Hosp, Dept Reprod Ctr, Jinan 250012, Peoples R China
[6] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Jinan 250011, Peoples R China
[7] Qianfo Hosp Shandong Prov, Jinan 250014, Peoples R China
关键词
Zuo-Gui-Wan; Bone loss; Estrogen deficiency; Th17/Treg paradigm; Transcription factor; Cytokine; T-CELLS; IMMUNE-SYSTEM; TH17; CELLS; OSTEOIMMUNOLOGY; WOMEN; HEALTH; TREG;
D O I
10.1016/j.jep.2015.03.011
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Ethnopharmacological relevance: Bone loss is a common pathological condition induced by estrogen deficiency. The Th17/Treg paradigm, which can be skewed by estrogen, plays an important role in regulating bone metabolism Aim of the study: The purpose of this study was to determine the role of the Th17/Treg shift in estrogen deficiency-induced bone loss in mouse models and to elucidate the immunopharmacologic mechanism of Zuo-Gui-Wan (ZGW) in preventing bone loss in this process by regulating Th17/Treg paradigm. Materials and methods: Splenocytes of ovariectomized (Ovx) mice and naturally aged mice were isolated and Flow cytometry was used to detect the Th17/Treg subsets. In addition, serum estrodiol (E-2) and serum C-terminal telopeptides of type I collagen (CTx) were detected by ELISA assay. Bone mineral density (BMD) of the left tibiae was measured by dual-energy X-ray absorptiometry. Moreover, Ovx mice were administrated with different doses of ZGW for 12 weeks, and BMD and Th17/Treg subsets were determined. Bone histomorphometry was observed by Hematoxylin and eosin (H&E) staining and serum protein levels of IL-6 were analyzed by ELISA assay. In addition, the mRNA and protein expression of ROR gamma t and Foxp3 were detected by RT-PCR and Western blot respectively. Result: The Th17/Treg paradigm shifted to Th17 in estrogen-deficient mice both in the Ovx mice and the naturally aged mice. BMD and E-2 levels negatively correlated with the Th17/Treg ratio. After ZGW administration, the BMD was enhanced markedly in the Ovx mice as well as in the naturally aged mice. Both the mRNA and protein expressions of IL-6 and ROR gamma t were decreased, whereas those of Foxp3 were increased significantly after ZGW administration. Conclusion: Th17/Treg shift involved in the bone loss induced by estrogen deficiency. ZGW prevented bone loss efficiently and skewed Th17/Treg paradigm towards Treg without enhancing E-2. (c) 2015 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:228 / 239
页数:12
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