Zuoguiwan Mitigates Oxidative Stress in Rat Model of Hyperthyroidism Due to Kidney-Yin Deficiency via DRD4/NOX4 Pathway
10.13422/j.cnki.syfjx.20251207
- VernacularTitle:基于DRD4/NOX4通路探讨左归丸改善肾阴虚型甲亢大鼠氧化应激的作用机制
- Author:
Ling LIN
1
;
Qianming LIANG
1
;
Changsheng DENG
1
;
Li RU
2
;
Zhiyong XU
2
;
Chao LI
2
;
Mingshun SHEN
2
;
Yueming YUAN
2
;
Muzi LI
3
;
Lei YANG
4
Author Information
1. Artemisinin Research Center， Guangzhou University of Chinese Medicine， Guangzhou 501405，China
2. Institute of Science and Technology，Guangzhou University of Chinese Medicine，Guangzhou 510445，China
3. Tong Ren Tang Technologies Co. Ltd.，Beijing 100079，China
4. School of Pharmaceutical Sciences，Guangzhou University of Chinese Medicine，Guangzhou 510006，China
- Publication Type:Journal Article
- Keywords:
hyperthyroidism due to kidney-Yin deficiency;
Zuoguiwan;
oxidative stress;
dopamine receptor D4 （DRD4）;
NADPH oxidase 4 （NOX4）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(2):43-51
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T3）， thyroxine （T4）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T3， T4， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T3， T4， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.
