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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2018, Vol. 23 ›› Issue (3): 283-289.doi: 10.12092/j.issn.1009-2501.2018.03.007

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Effects of platelet activation on renal tubular epithelial cells in sepsis

FANG Jingjing, TAO Jing, HUANG Qin, SHI Chaolu, YAN Biqing, GAI Lei, LI Xuguang   

  1. Intensive Care Unit,the Affiliated Hospital of Medical College of Ningbo University, Ningbo 315020, Zhejiang, China
  • Received:2017-11-10 Revised:2018-02-28 Online:2018-03-26 Published:2018-03-28

Abstract:

AIM: To investigate the effect of platelet activation on renal tubular epithelial cells in sepsis. METHODS: ELISA was used to detect the inflammatory cytokines IL-1β and IL-6 secreted by platelets. Renal tubular epithelial cells and platelets were co-cultured in the co-culture system. Western blot was used to test p65 and p-p65 protein in renal tubular epithelial cells in the lower chamber. IL-1β and IL-6 mRNA expression level was measured by qRT-PCR. Cecal ligation and puncture(CLP) were used to construct the sepsis model, and TLR4 inhibitor TAK-242 was injected in caudal vein. In order to observe injury degree of renal tissue, EdU experiment and serum creatinine detection were carried out. RESULTS: IL-1β and IL-6 cytokines secreted by active platelets were increased in the presence of different concentrations of LPS. In the platelet and renal tubular epithelial cells co-culture system, p-p65 protein was increased in the tubular epithelial cells. TAK-242 could inhibit platelet activation, and reduce the renal tubular epithelial cell inflammatory cytokines secretion.The proliferation and pathological status were improved, and serum creatinine was decreased. CONCLUSION: The platelets in septic patients are aggregated and activated. inflammatory cytokines are increased. These cytokines activate NF-κB signaling pathway of renal tubular epithelial cells, leading to renal injury. TLR4 inhibitors have potential clinical value to improve the renal injury in sepsis. 

Key words: sepsis, kidney injury, platelet activation, NF-κB signaling pathway

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