FAN Yanmin,SONG Chundong,SHI Huiyuan,et al.Protective effect of Shenbining granule on renal tissue of IgA nephropathy rats based on mitochondrial quality control system[J].ZHONGGUO YAOFANG,2024,35(24):2984-2989.
FAN Yanmin,SONG Chundong,SHI Huiyuan,et al.Protective effect of Shenbining granule on renal tissue of IgA nephropathy rats based on mitochondrial quality control system[J].ZHONGGUO YAOFANG,2024,35(24):2984-2989. DOI: 10.6039/j.issn.1001-0408.2024.24.04.
Protective effect of Shenbining granule on renal tissue of IgA nephropathy rats based on mitochondrial quality control system
To explore the renal protective mechanism of Shenbining granules on IgA nephropathy (IgAN) rats based on mitochondrial quality control system.
METHODS
2
IgAN rat model was established by the method of “bovine serum albumin+carbon tetrachloride+lipopolysaccharide”. The model rats were randomly divided into model group, prednisone acetate group (6.25 mg/kg), Shenbining equal-dose group (4.1 g/kg) and Shenbining high-dose group (20.5 g/kg). The normal rats were taken as the normal control group, with 12 rats in each group. Rats were given corresponding drugs or distilled water intragastrically in each group, once a day, for 4 consecutive weeks. After the last medication, the 24 h total urinary protein (24 h-UTP) and erythrocyte count in urine were determined, and the levels of serum creatinine (Scr), blood urea nitrogen (BUN), albumin (ALB) and alanine transaminase (ALT) were also detected. The histopathological changes in the kidneys and changes in IgA deposition in the mesangial area of the kidney were observed. mRNA and protein expression levels of PTEN-induced putative kinase 1 (PINK1), E
3
ubiquitin ligase (Parkin), microtubule-associated protein 1 light chain-3 (LC3), dynamin-related protein 1 (Drp1) and mitofusin 2 (Mfn2) were detected in the kidney tissues of rats.
RESULTS
2
Compared with model group, 24 h-UTP, urinary erythrocyte count, ALT, BUN and Scr levels, LC3-Ⅱ/LC3-Ⅰ mRNA ratio, mRNA and protein expressions of Drp1 were reduced significantly in prednisone acetate group, Shenbining equal-dose group and Shenbining high-dose group (
P
<0.05); ALB level, LC3-Ⅱ/LC3-Ⅰ protein ratio, mRNA and protein expressions of PINK1, Parkin and Mfn2 were increas
ed significantly (
P
<0.05); the pathological morphology of kidney tissue in rats was significantly improved, and IgA deposition was significantly reduced.
CONCLUSIONS
2
Shenbining granule may reduce renal pathological injury in IgAN rats and protect renal function by activating the PINK1/Parkin pathway, enhancing mitochondrial autophagy, and correcting mitochondrial kinetic disorders.
关键词
Keywords
references
TIAN Z Y , LI Z , CHU L , et al . Iron metabolism and chronic inflammation in IgA nephropathy [J ] . Ren Fail , 2023 , 45 ( 1 ): 2195012 .
SALVADÈ V , TETA D , GUZZO G . IgA nephropathy:the beginning of a new therapeutic era [J ] . Rev Med Suisse , 2024 , 20 ( 863 ): 445 - 450 .
TAN Z X , ZHU W Z . Regulatory mechanisms of mitochondrial dynamics and its emerging role in renal pathophysiology [J ] . Acta Physiol Sin , 2024 , 76 ( 1 ): 148 - 160 .
ZHANG M T , LI Y Y , ZHANG L . Regulation of mitochondrial quality control in treatment of diabetic kidney disease by traditional Chinese medicine:a review [J ] . Chin J Exp Tradit Med Formulae , 2023 , 29 ( 4 ): 236 - 245 .
ZHOU H , REN J , TOAN S , et al . Role of mitochondrial quality surveillance in myocardial infarction:from bench to bedside [J ] . Ageing Res Rev , 2021 , 66 : 101250 .
DONG Y M , ZHANG X . Targeting cellular mitophagy as a strategy for human cancers [J ] . Front Cell Dev Biol , 2024 , 12 : 1431968 .
CUI Y L , SONG M , XIAO B N , et al . ROS-mediated mitophagy and apoptosis are involved in aluminum-induced femoral impairment in mice [J ] . Chem Biol Interact , 2021 , 349 : 109663 .
JIANG H R , SONG C D , DUAN F Y , et al . Protective effect of Shenbining granule on renal tissue of IgA nephropathy rats based upon SphK1/S1PR2 pathway [J ] . Chin J Hosp Pharm , 2024 , 44 ( 11 ): 1246 - 1252 .
TANG Y , LOU T Q , CHENG C L , et al . Improvement of experimental IgA nephropathy model [J ] . J Sun Yat Sen Univ Med Sci , 2006 , 27 ( 2 ): 184 - 187 .
HUANG J H , HUANG X H , CHEN Z Y , et al . Dose conversion among different animals and healthy volunteers in pharmacological study [J ] . Chin J Clin Pharmacol Ther , 2004 , 9 ( 9 ): 1069 - 1072 .
ZHANG X M , ZHOU J B , YANG F , et al . Research pro-gress of mitochondrial dysfunction regulating mechanism of chronic kidney disease and traditional Chinese medicine treatment [J ] . Chin Arch Tradit Chin Med , 2024 , 42 ( 3 ): 198 - 202 .
LIU Y , GUO Y F , LIU Z Y , et al . Augmented temperature fluctuation aggravates muscular atrophy through the gut microbiota [J ] . Nat Commun , 2023 , 14 ( 1 ): 3494 .
GU X T , LI X N . Research progress on the role and mechanism of mitochondrial dynamics and mitophagy in ischemic stroke [J ] . J Neurosci Ment Health , 2023 , 23 ( 5 ): 328 - 333 .
ZHANG X , LIU N M , MA J Y , et al . Effect of mitochondrial fission/fussion protein expression imbalance in pathological changes of kidney tissue in IgA nephropathy mice [J ] . J Jilin Univ(Med Ed) , 2021 , 47 ( 2 ): 284 - 291 .
SULKSHANE P , RAM J , THAKUR A , et al . Ubiquitination and receptor-mediated mitophagy converge to eliminate oxidation-damaged mitochondria during hypoxia [J ] . Redox Biol , 2021 , 45 : 102047 .
QI Z H , HUANG Z , XIE F , et al . Dynamin-related protein 1:a critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases [J ] . J Cell Physiol , 2019 , 234 ( 7 ): 10032 - 10046 .
CHEN X , SU Q , GONG R Z , et al . LC3-associated phagocytosis and human diseases:insights from mechanisms to therapeutic potential [J ] . FASEB J , 2024 , 38 ( 20 ): e70130 .