Study on the mechanism of regulating bile acid metabolism to improve diabetic encephalopathy by Zishenwan Prescription
10.3760/cma.j.cn115398-20230808-00083
- VernacularTitle:滋肾丸方调控胆汁酸代谢改善糖尿病脑病作用机制研究
- Author:
Ping LIU
1
;
Genhui YANG
;
Fanyu MENG
;
Ying LI
;
Mengxi XU
;
Hong GUO
;
Yanjun ZHANG
;
Qingsheng YIN
;
Pengwei ZHUANG
Author Information
1. 天津中医药大学中药学院，天津 301617
- Keywords:
Bile acid;
Metabolism;
Diabetic encephalopathy;
Zishenwan Prescription;
FXR-FGF15/FGFR4 signaling pathway;
Mice
- From:
International Journal of Traditional Chinese Medicine
2024;46(7):860-866
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To examine the effects of Zishenwan Prescription on bile acid metabolism in mice with diabetic encephalopathy; To explore its mechanism of improvement of diabetic encephalopathy.Methods:Male C57BL/6J mice were used to replicate the mouse model of type 2 diabetes mellitus by using high-fat chow and a single intraperitoneal injection of streptozotocin (120 mg/kg). The mice were screened for diabetic encephalopathy by using the Morris water maze test after 8 weeks of continuous stimulation with hyperglycemia, and were divided into model group and Zishenwan Prescription group according to random number table method, with 12 mice in each group. The mice in the Zishenwan Prescription group were treated with the crude extract of Zishenwan Prescription (9.36 g/kg) by gavage, and the normal group and the model group were treated with the same volume of distilled water once a day for 8 weeks. At the end of the treatment, Morris water maze test was used to investigate the cognitive function of diabetic encephalopathy mice; cresyl violet staining was used to detect the number of granule neurons in the hippocampus; serum and feces were collected to detect the content of bile acids by liquid-liquid coupling; hepatic bile acid synthase CYP7a1 and CYP27a1, farnesol X receptor (FXR), fibroblast growth factor 15 (FGF15), fibroblast growth factor receptor 4 (FGFR4), and ileocecal apical sodium-dependent bile acid transporter protein (ABST) mRNA levels were detected by using fluorescence quantitative PCR assay.Results:Compared with the model group, mice in the Zishenwan Prescription group had shorter evasion latency time ( P<0.05 or P<0.01), decreased time to first reach the platform ( P<0.01), increased number of times to traverse the platform ( P<0.01), and reduced neuronal cell damage in hippocampal area; mice in the Zishenwan Prescription group showed decreased serum and fecal total bile acid content ( P<0.05 or P<0.01); the liver CYP7a1 and CYP27a1 mRNA expressions increased ( P<0.01), and FXR and FGF15 mRNA expressions decreased ( P<0.01); ileal ABST mRNA expression decreased ( P<0.01). Conclusion:Zishenwan Prescription may regulate bile acid metabolism, inhibit FRX-FGF15/FGFR4 signaling and ABST expression to promote new bile acid synthesis and conjugated bile acid reabsorption, and thus improve cognitive function in diabetic encephalopathy mice.
