Mechanism of Modified Shenqiwan in Relieving Renal Interstitial Fibrosis in Diabetic Mice Based on GSK-3β/CREB Pathway
10.13422/j.cnki.syfjx.20230702
- VernacularTitle:基于GSK-3β/CREB信号通路探讨加味肾气丸减轻糖尿病小鼠肾间质纤维化的作用机制
- Author:
Jiahua ZHANG
1
;
Hongyue NING
1
;
Liping AN
2
;
Pinchuan JI
2
;
Bai CHANG
3
;
Haowen QI
2
;
Jianen GUO
1
Author Information
1. Chengde Medical University，Chengde 067000，China
2. Chengde Hospital of Traditional Chinese Medicine，Chengde 067000，China
3. Zhu Xianyi Memorial Hospital of Tianjin Medical University，Tianjin 300134，China
- Publication Type:Journal Article
- Keywords:
Shenqiwan;
diabetic nephropathy;
glycogen synthase kinase-3β （GSK-3β）;
cAMP response element-binding protein （CREB）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(16):162-169
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effects of modified Shenqiwan on renal function and fibrosis in diabetic nephropathy mice and explore the underlying mechanism based on the glycogen synthase kinase-3β （GSK-3β）/cyclic adenosine monophosphate （cAMP） response element-binding protein （CREB） signaling pathway. MethodFifty male db/db mice and 10 db/m mice were used in this study. The fifty db/db mice were randomly divided into model group， irbesartan group， and low-， medium-， and high-dose modified Shenqiwan groups. The 10 db/m mice were assigned to the normal group. The mice in the low-， medium-， and high-dose modified Shenqiwan groups were administered with modified Shenqiwan in the dosage form of suspension of Chinese medicinal granules by gavage， those in the irbesartan group were given irbesartan suspension by gavage， and those in the normal and model groups were given distilled water of equal volume by gavage. The intervention lasted for 12 weeks. The blood glucose levels， urine albumin-to-creatinine ratio （UACR）， and the protein expression levels of GSK-3β， CREB， transforming growth factor-β1 （TGF-β1）， E-cadherin， Vimentin， fibronectin （FN）， plasminogen activator inhibitor-1 （PAI-1）， and Collagen type Ⅳ （Coll Ⅳ） in the mouse kidneys were recorded before and after treatment. The extent of renal pathological damage was also observed. ResultCompared with the normal group， the model group showed significant increases in blood glucose levels， UACR levels， and the protein expression levels of GSK-3β， TGF-β1， E-cadherin， Vimentin， FN， PAI-1， and Coll Ⅳ in the kidneys （P<0.05）， decreased protein expression level of CREB （P<0.05）， and severe renal pathological damage. Compared with the model group， the low-， medium-， and high-dose modified Shenqiwan groups and the irbesartan group showed varying degrees of decreases in blood glucose levels， UACR levels， and the protein expression levels of GSK-3β， TGF-β1， E-cadherin， Vimentin， FN， PAI-1， and Coll Ⅳ in the kidneys （P<0.05）， increased expression level of CREB protein （P<0.05）， and improved renal pathological damage. ConclusionModified Shenqiwan can effectively reduce blood glucose levels， improve renal function， and alleviate fibrosis， and the mechanism of action is related to the inhibition of the GSK-3β/CREB signaling pathway.
