Study on neurogenic bladder-induced renal fibrosis based on AngⅡ/TGF-β1/Smads signaling pathway
10.3760/cma.j.cn441217-20201022-00151
- VernacularTitle:基于AngⅡ/TGF-β1/Smads信号通路关于神经源性膀胱诱导肾脏纤维化的研究
- Author:
Yan ZHENG
1
;
Yuan MA
;
Xuejing REN
;
Peiyuan NIU
;
Lei YAN
;
Huixia CAO
;
Fengmin SHAO
Author Information
1. 河南省人民医院（郑州大学人民医院）肾内科，河南省肾脏病免疫重点实验室，郑州 450003
- Keywords:
Kidney;
Fibrosis;
AngiotensinⅡ;
Transforming growth factor beta1;
Smads;
Signaling pathway
- From:
Chinese Journal of Nephrology
2021;37(12):1001-1007
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To establish a rat model of neurogenic bladder and analyze the changes in kidney morphology and function and the expression of proteins in AngiotensinⅡ(AngⅡ)/transforming growth factor β1 (TGF-β1)/Smads pathway.Methods:Sprague-Dawley rats were randomly divided into experimental group (spinal nerve amputation, n=36) and control group (sham operation, n=12). At 6, 12, and 24 weeks, the bladder compliance was measured by cystometry, the kidney morphology was detected by B-ultrasound, blood urea nitrogen (BUN) and serum creatinine (Scr) in blood samples were examined, the kidney pathological changes were detected by Masson and HE staining, the distribution of AngⅡ/TGF-β1/Smads pathway proteins was analyzed by immunohistochemisty, and the protein expressions in kidney were detected by Western blotting. Results:Urodynamics showed that the basic bladder pressure in experimental group was higher than that in control group. B-ultrasound showed that compared with the control group, the diameter of the renal pelvis of the rats with nerve dissection gradually increased ( P<0.05), and the hydronephrosis was gradually obvious. Compared with the control group, the BUN and Scr in experimental group gradually increased (both P<0.01). Masson and HE staining showed that compared with the control group, the collagen expression and renal tubulointerstitial scores in experimental group were gradually increased (both P<0.01). Immunohistochemisty showed that compared with the control group, in experimental group the expression of angiotensinⅡ receptor type 1 (AT1), TGF-β receptor 1(TGF-βR1), phosphorylated Smad2 gradually increased (all P<0.01), the pathway inhibitor Smad6 gradually decreased ( P<0.01), and the distribution of each protein in kidney was consistent. Western blotting showed a corresponding expression trend with immunohistochemisty. Conclusions:In neurogenic bladder caused by bilateral spinal nerve amputation, due to bladder dysfunction, increased bladder pressure induces hydronephrosis, destruction of the nephron structure, activation of AngⅡ/TGF-β1/Smads pathway, and renal fibrosis. This method is effective and has clinical similarities, laying a foundation for exploring neurogenic bladder treatment.
