Role of glucocorticoid receptor and nuclear factor kappa B in rat hepatic injury after traumatic hemorrhagic shock

Abstract


Donglin Luo, Xiankai Huang*, Baohua Liu, Xiaobao Ren, Renping Xiong, Tao Li and Guangyan Li

The present study investigated expressions and functions of glucocorticoid receptor (GR) and nuclear factor kappa B (NF-B) in rat livers after traumatic hemorrhagic shock. The rat model of bilateral femur fracture accompanied with traumatic hemorrhagic shock was established. 96 male Wistar rats were randomly divided into normal control group (n = 6), traumatic shock group (n = 30), GR blocking group (n = 30) and NF-B inhibiting group (n = 30). 10 g/L of Ru486 (Mifepristone) was given via intramuscular injection 1.5 h before injury to block GR expression in GR blocking group, and 200 mg/kg of pyrrolidine dithiocarbamate (PDTC) was given via intraperitoneal injection 1 h before injury to inhibit the activity of NF-B. The expression of GR, TNF- and IL-6, the activity of NF-B, the hepatic pathology and the hepatic function were dynamically observed 0.5, 2, 4, 6, 8 h after trauma. Electrophoretic mobility shift assay (EMSA) was used to detect the bind activity of NF-B. The content of GR protein in liver tissue started to decrease 2 h after traumatic hemorrhagic shock, and was significantly lower than the normal control group after 4 h (P < 0.01). The activity of NF-B was significantly increased after injury, and peaked after 6 h (P < 0.01). After blocking GR expression, NF-B expression was significantly increased at each time point after reinjury. Two hours after injury, inflammatory cell infiltration was observed in the Sinus hepaticus. The expressions of TNF - , IL-6, ALT and TB were significantly increased 2 h after injury (P < 0.01). After inhibiting NF -B, GR expression was increased in liver tissue after reinjury. TNF-and IL-6 were rapidly decreased at each time point after injury. The liver cell degeneration was significantly recovered 4 - 8 h after injury under light microscope and the congestion in the S. hepaticus was relieved. ALT and TB expressions in serum were significantly decreased 4 h after injury. GR and NF-B have a close relationship and play an important role in the hepatic injury after traumatic hemorrhagic shock.

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