[Study on therapeutic effect and its related mechanism of anemoside B4 on ischemia reperfusion injury induced by renal artery and vein ligation in rats]

Zhongguo Zhong Yao Za Zhi. 2020 Feb;45(3):617-622. doi: 10.19540/j.cnki.cjcmm.20191209.401.
[Article in Chinese]

Abstract

The aim of this paper was to investigate the effect and mechanism of anemoside B4 on renal ischemia reperfusion injury in rats. A total of 50 rats were randomly divided into the model group(NS) and anemoside B4 low-dose(1.25 mg·kg~(-1)), medium-dose(2.5 mg·kg~(-1)) and high-dose(5 mg·kg~(-1)) groups after the right kidney was removed and the left kidney was ligated to make the ischemia reperfusion model. Another 10 rats were selected as sham operation group only for normal control group(NS, received normal saline). Automatic biochemical analyzer was used to measure serum blood urea nitrogen(BUN), creatinine(Cre), cerebrospinal fluid(CSF) and urinemicroalbumin(mALB) levels after 5 days of tail vein injection treament. Total urine protein and total urinary albu-min were calculated and kidney samples were collected. Histopathological changes of renal tissues were observed by PAS staining. Western blot analysis was performed to detect the protein expressions of TLR4 and NF-κB in renal inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway. The results showed that the levels of BUN, Cre, urinary total protein and urinary total albumin in the model group were significantly increased(P<0.01), with severe renal tubule injury was serious, manifested by obvious expansion of renal tubules, more serious tubular proteins, and some tubular epithelial cells were exfoliated. At the same time, the expression of inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway increased significantly(P<0.01 or P<0.05). The levels of BUN, Cre were reduced in different doses of anemoside B4(P<0.05). The levels of total urinary protein and total urinary albumin were decreased in the low and high dose groups of anemoside B4.The level of total urinary albumin in the high-dose group of anemoside B4 was significantly reduced(P<0.05).Renal tubular injury was alleviated, tubular epithelial cell exfoliation was reduced, and the expression of related inflammatory factors was reduced in different degrees(P<0.01 or P<0.05). This study showed that anemoside B4 could alleviate renal ischemia-reperfusion injury in rats. And its mechanism may be related to the inhibition of inflammatory factors related to response mediated by NLRP3 pathway and TLR4/NF-κB pathway by anemoside B4.

Keywords: NLRP3 inflammasome; TLR4/NF-κB; anemoside B4; renal ischemia reperfusion.

MeSH terms

  • Animals
  • Kidney
  • Ligation
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Rats
  • Renal Artery / pathology*
  • Reperfusion Injury / drug therapy*
  • Saponins / therapeutic use*
  • Signal Transduction*
  • Toll-Like Receptor 4 / metabolism

Substances

  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Saponins
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • anemoside B4