ISSN 2326-7267
International Journal of Pharmacy and Pharmacology ISSN: 2326-7267 Vol. 7 (1), pp. 001-008, January, 2018. © International Scholars Journals
Full Length Research Paper
Role of glucocorticoid receptor and nuclear factor kappa B in rat hepatic injury after traumatic hemorrhagic shock
Donglin Luo1, Xiankai Huang2*, Baohua Liu1, Xiaobao Ren3, Renping Xiong1, Tao Li1 and Guangyan Li1
1Department of General Surgery, Institute of Battle Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
2Trauma Center, Institute of Battle Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
3Department of Emergency, Southwestern Hospital, Third Military Medical University, Chongqing 400038, China.
Accepted 24 November, 2017
Abstract
The present study investigated expressions and functions of glucocorticoid receptor (GR) and nuclear factor kappa B (NF-kB) 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-kB 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-kB. The expression of GR, TNF- and IL-6, the activity of NF-kB, 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-kB. 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-kB was significantly increased after injury, and peaked after 6 h (P < 0.01). After blocking GR expression, NF-kB 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 -kB, 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-kB have a close relationship and play an important role in the hepatic injury after traumatic hemorrhagic shock.
Key words: Trauma, hemorrhagic shock, glucocorticoid receptor, nuclear factor kappa B, liver injury.