Effects of nuclear factor kappa B(NF-κB)inhibition on heat shock protein 70(HSP 70)expression in a rodent model of hemorrhagic shock / 中华急诊医学杂志

ABSTRACT

Objective To study the effects of the inhibition of nuclear factor kappa-B ( NF-κB) , on the hepatic heat shock protein 70 (HSP70) expression as well as on the changes of hepatic function and ultrastructure in a rodent model of hemonhageic shock. Method Hemorrhagic shock was produced by inducing bilateral femoral fractures in male Wistar rats. Intraperitoneal injection of pyrrolidine dithiocarbamate(PDTC)was used to inhibit NF-κB activation 1 hour before induction of shock. A total of 66 adult male Wistar rats were randomly divided into 3 groups control group (Control, n = 6), trauma shock (TS, n = 30), and NF-κB inhibition followed by trauma shock (NF-κB inhibition, n =30). Measurements of hepatic NF-KB and HSP70, hepatic function bio-markers, TNF-α and IL-6 were obtained 0.5, 2, 4, 6, 8 hours after trauma. Histopathological changes in liver tissues were also noted. Hepatic expression of NF-κB was determined by using electrophoretic mobility shift assay, while HSP70 was assayed by western blot and analyzed with computer imaging. Results In rats with trauma shock, both hepatic NF-κB activity and HSP70 expression increased significantly compared to the control group, reaching peaks at 6 hour post injury. Serum alanine transferase (ALT) and total bilirubin (TB) also rose significantly,reaching peaks at 8 hours post trauma. Light microscopy revealed hepatic congestion with infiltration of inflammatory cells into hepatic sinusoid in the TS group at 8 hours. Inhibiting the activity of NF-κB one hour before trauma significantly decreased expression of HSP70 at 6 hours post trauma [16.9±4.4 (NF-κB inhibition) vs. 23.0±1.7 (TS), P ＜ 0.05]. In addition,levels TNF-α and IL-6 in the liver tissue also decreased, and hepatic congestion as well as hepatic cell degeneration were ameliorated, showing minimal inflammatory infiltrates in the hepatic sinusoids. NF-κB inhibition also significantly lowered the levels of ALT and TB at 4 hours post trauma [ALT, 540.8 ±66.2 nmol/L (NF-KB inhibition) vs. 640.6±80.2 nmol/L (TS), P ＜ 0.05; TB,2.3±0.3 mol/L (NF-κB inhibition) vs. 4.7 ±1.1 mol/L (TS), P ＜ 0.05]. Conclusions NF-κB and HSP70 are involved in the pathogenesis of hepatic injury during hemorrhagic shock, and the degree of NF-κB activity and HSP70 expression may be consistent with the extent of hepatocellular damage. Inhibition of NF-κB helps ameliorate liver injury due to trauma shock.