ACTA NEUROPHARMACOLOGICA››2021,Vol. 11››Issue (1): 1-64.DOI:10.3969/j.issn.2095-1396.2021.01.001

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Betulinic Acid Ameliorates Rhabdomyolysis-Induced Acute Kidney Injury by Inhibiting the Phosphorylation of P38 Mitogen-Activated Protein Kinases in Rats#br# #br#

ZHANG Chao

  1. Department of Nephrology,No. 980 Hospital of Chinese People’s Liberation Army Joint Logistic Support Force(Bethune International Peace Hospital of Chinese PLA),Shijiazhuang,050051,China
  • Online:2021-02-26Published:2021-02-26
  • Contact:Zhang Chao,Email:zhangchao0724@126.com

Abstract:

Objective:To investigate the change and effect of P38 MAPK in rhabdomyolysis-induced acute kidney injury (AKI) and the interfered effect of betulinic acid (BA). Methods:40 Wistar rats were randomly divided into 5 groups:control group( C),group AKI( A),group AKI+BA( AB),group AKI+SB203580( AS),group AKI+BA+SB203580( ABS). The experimental model of rhabdomyolysis-induced AKI was established by injecting 50% glycerin intramuscular into the hind limbs. Group AB,AS and ABS were administered intraperitoneally with BA and SB203580 separately or together. 24 hours after glycerin injection,the venous blood and kidney samples were taken. The serum creatinine( CR),blood urea nitrogen( BUN) and creatine kinase( CK) were detected with automatic biochemistry analyzer. The expression of pP38 MAPK,P38 MAPK and cleaved caspase-3 in kidney were assayed by Western Blot. The pathological changes were examined by H&E staining. The levels of TNFα and IL6
in kidney were measured by ELISA. Results:Glycerin injection induced acute injury and pP38/P38 ratio was higher in the kidney,which were ameliorated by administration of BA and SB203580. In the dosage of this experiment,BA had better curative effect on renal function,kidney injury score,apoptosis rate and IL-6 level than SB203580. But the inhibition of P38 phosphorylation of SB203580 was stronger than BA. The influence on TNF-α of both drugs were similar. Generally,combined treatment of the two drugs had no significant difference with BA alone. Conclusion:In rhabdomyolysis-induced AKI,P38 MAPK was activated. Inhibition of P38 phosphorylation by SB203580 could reduce the level of Cr and BUN,suppress renal inflammation,alleviate the pathological damage and apoptosis. BA played a renoprotective role at least partially through inhibit ing the phosphorylation of P38 MAPK.

Key words:rhabdomyolysis,acute kidney injury,betulinic acid,P38 mitogen activated protein kinase,inflammatory reaction

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