QiDiTangShen granules modulated the gut microbiome composition and improved bile acid profiles in a mouse model of diabetic nephropathy.

QiDiTangShen granules modulated the gut microbiome composition and improved bile acid profiles in a mouse model of diabetic nephropathy.
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芪地糖肾颗粒可调节糖尿病肾病小鼠模型的肠道微生物组组成并改善胆汁酸谱。

DOI:
10.1016/j.biopha.2020.111061
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发表时间:
2021-01
期刊:
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
影响因子:
--
通讯作者:
Yang Shi
Yang Shi
中科院分区:
其他
文献类型:
--
作者:
Xianhui Zhang;Weijing Liu;Huidi Xie;Lin Wang;Qing Du;Huili Wei;Hongfang Liu;Zhichao An;Xi Wu;Yan Guo;Sicheng Li;Yang Shi

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芪脂糖肾颗粒(QDTS)是一种传统的中草药,用于临床治疗糖尿病肾病已有多年的历史。在我们之前的研究中,我们已经证明了QDTS对糖尿病肾病(DN)小鼠的蛋白尿有很好的减少作用。然而,QDTS发挥其肾保护作用的确切机制在很大程度上仍然未知。为了确定QDTS是否能靶向肠道微生物-胆汁酸轴,我们采用db/db小鼠作为DN小鼠模型。经过12周的治疗,我们发现QDTS显著降低了db/db小鼠的尿白蛋白排泄量(UAE),减轻了肾脏的病理损伤,而这些小鼠的体重和血糖水平没有受到影响。此外,我们发现QDTS显著改变了肠道菌群组成,降低了血清总胆汁酸(TBA)水平和BA谱,如β-胆酸(β-MCA)、牛磺胆酸(TCA)、牛磺酸β-胆酸(t - β-MCA)和脱氧胆酸(DCA)。这些BAs与farnesoid X受体(FXR)的激活有关,FXR在肾脏中高度表达。然而,在qdts治疗和未治疗的db/db小鼠中,FXR的肾脏表达没有显著差异,表明可能涉及其他机制。总之,我们的研究表明,QDTS显著减轻了DN小鼠的肾脏损伤。肠道微生物-胆汁酸轴可能是QDTS在DN中肾保护的重要靶点,但具体机制有待进一步研究。
QiDiTangShen granules (QDTS), a traditional Chinese herbal medicine, have been used in clinical practice for treating diabetic kidney disease for several years. In our previous study, we have demonstrated that QDTS displayed good efficacy on reducing proteinuria in mice with diabetic nephropathy (DN). However, the exact mechanism by which QDTS exerts its reno-protection remains largely unknown. To ascertain whether QDTS could target the gut microbiota-bile acid axis, the db/db mice were adopted as a mouse model of DN. After a 12-week of treatment, we found that QDTS significantly reduced urinary albumin excretion (UAE), and attenuated the pathological injuries of kidney in the db/db mice, while the body weight and blood glucose levels of those mice were not affected. In addition, we found that QDTS significantly altered the gut microbiota composition, and decreased serum levels of total bile acid (TBA) and BA profiles such as β-muricholic acid (β-MCA), taurocholic acid (TCA), tauro β-muricholic acid (Tβ-MCA) and deoxycholic acid (DCA). These BAs are associated with the activation of farnesoid X receptor (FXR), which is highly expressed in kidney. However, there was no significant difference between QDTS-treated and -untreated db/db mice regarding the renal expression of FXR, indicating that other mechanisms may be involved. Conclusively, our study revealed that QDTS significantly alleviated renal injuries in mice with DN. The gut microbiota-bile acid axis may be an important target for the reno-protection of QDTS in DN, but the specific mechanism merits further study.
DOI: 10.1155/2018/6093282
发表时间: 2018
期刊: Evidence-based complementary and alternative medicine : eCAM
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