Effect of Heat Shock Protein 70 on Inducible Nitric Oxide Synthase during Sepsis in Rats

ABSTRACT

PURPOSE: The aim of this study was to evaluate the effect of overexpression of heat shock protein 70 (HSP70) on the expression of inducible nitric oxide synthase and on the concentration of nitric oxide and to determine the mechanism for the relationship between HSP70 and inducible nitric oxide synthase (iNOS) in sepsis. METHODS: Experiments were performed on male Sprague-Dawley rats, and sepsis was induced by using cecal ligation and puncture (CLP). Glutamine (GLN) or saline was administered 1 h after initiation of sepsis. We acquired serum and lung tissues from the rats 12 h or 24 h after initiation of sepsis. We analyzed the concentration of nitric oxide, the expression of HSP70 in the lung, and the gene expression of iNOS in the lung. RESULTS: In CLP+GLN, glutamine given after initiation of sepsis enhanced the expression of HSP70 in the lung at 12 h (CLP+GLN vs. CLP 47.19 +/- 10.04 vs. 33.22 +/- 8.28, p = 0.025) and 24 h (CLP+GLN vs. CLP 47.06 +/- 10.60 vs. 31.90 +/- 4.83, p = 0.004). In CLP+GLN, glutamine attenuated the expression of iNOS mRNA in the lung at 12 h (CLP+GLN vs. CLP 4167.17 +/- 951.59 vs. 5513.73 +/- 1051.60, p = 0.025) and 24 h (CLP+GLN vs. CLP 9,437.65 +/- 2,521.07 vs. 18,740.27 +/- 8,241.20, p = 0.016) and reduced the concentration of nitric oxide in serum at 12 h (CLP+GLN vs. CLP 0.86 +/- 0.48 vs. 3.82 +/- 2.53 micromol/L, p = 0.016) and 24 h (CLP+GLN vs. CLP 0.39 +/- 0.25 vs. 1.85 +/- 1.70 micromol/L, p = 0.025). CONCLUSION: The overexpression of HSP70 induced by the administration of glutamine in sepsis attenuated the gene expression of iNOS and reduced the concentration of nitric oxide.