Anti-inflammatory Mechanism of Wuwei Xiaoduyin on IgA Nephropathy Rats Based on NF-κB Inflammatory Signaling Pathway
10.13422/j.cnki.syfjx.20210804
- VernacularTitle:基于NF-κB炎症通路探讨五味消毒饮对IgA肾病大鼠的抗炎机制
- Author:
Yu ZHANG
1
;
Guang-wei WANG
1
;
Zhe LYU
2
;
Deng-zhou GUO
1
Author Information
1. Hebei University of Chinese Medicine，Shijiazhuang 050091，China
2. Hebei Hospital of Traditional Chinese Medicine，Shijiazhuang 050011，China
- Publication Type:Research Article
- Keywords:
immunoglobulin （Ig）A nephropathy;
Wuwei Xiaoduyin;
nuclear factor-κB （NF-κB）;
inflammatory response;
proteinuria
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(10):15-22
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effect of Wuwei Xiaoduyin on the nuclear factor-κB （NF-κB） signaling pathway in immunoglobulinA nephropathy（IgAN） rats， and to explore its mechanism of action in the treatment of IgA nephropathy. Method:The 40 SD rats were randomly divided into control group， model group， benazepril group （10 mg·kg·d-1） and Wuwei Xiaoduyin group （2.75 g·kg·d-1）， with 10 rats in each group. The IgA nephropathy rat model was established by intragastric administration of bovine serum albumin （BSA）， subcutaneous injection of carbon tetrachloride （CCl4） and tail vein injection of lipopolysaccharide （LPS） for 9 weeks. The rats in each group were given corresponding doses of drugs by gavage， while the rats in the control group and model group were given the same amount of normal saline for successive 28 days. The levels of 24-hour urinary protein （UTP）， serum creatinine （SCr）， blood urea nitrogen （BUN） and serum albumin （ALB） were detected. The contents of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and interleukin-6 （IL-6） in serum were detected by enzyme-linked immunosorbent assay （ELISA）， the hematoxylineosin staining （HE）， immunofluorescence and transmission electron microscopy were used to observe the renal pathological changes， the expressions of IL-6， IκB kinase β （IKKβ）， phosphorylated IκB kinase β （p-IKKβ）， NF-κB inhibitor protein α （IκBα）， phosphorylated NF-κB inhibitor protein α （p-IκBα）， NF-κB p65 and p-NF-κB p65 were detected by immunohistochemistry （IHC）， real-time PCR （RT-PCR） and Western blot， respectively. Result:Compared with the control group， the level of UTP in the model group significantly increased （P<0.01）， cultured glomerular mesangial cells proliferated， mesangial matrix and electronic dense deposit increased， mesentery thickened. A large amount of IgA was deposited in the glomerular mesangial area and showed irregular particles and mass distribution， the levels of TNF-α， IL-1β， IL-6 in serum significantly increased （P<0.01）， the expression levels of IL-6， IKKβ， p-IKKβ， NF-κB p65 and p-NF-κB p65 in renal tissue significantly increased （P<0.01）.Compared with the model group， the levels of UTP in each administration group significantly decreased （P<0.01）， and the renal tissue injury alleviated， the levels of TNF-α， IL-1β， IL-6 in serum significantly decreased （P<0.01）， the expressions of IL-6， IKKβ， p-IKKβ， IκBα， p-IκBα， NF-κB p65 and p-NF-κB p65 in the renal tissue significantly decreased （P<0.01）. There were no significant differences in serum creatinine， blood urea nitrogen and serum albumin among the groups. Conclusion:Wuwei Xiaoduyin can reduce proteinuria in IgA nephropathy rats， and its mechanism may be related to the inhibition of NF-κB signaling pathway and the over expression of related inflammatory factors.
