BACKGROUND: The complicated pathogenesis of systemic inflammatory response syndrome (SIRS) is a hot topic in critical care medicine. In this study we explored the expression of toll-like receptor (TLR) 2, 4 of livers in SIRS mice and evaluated the role of TLR2, 4 in the pathogenesis of SIRS. METHODS: Forty BABL/C mice were randomly divided into 2 groups: control (n=20) and SIRS (n=20). SIRS model was induced by severe acute pancreatitis. Blood routine, blood amylase, glutamic pyruvic transaminase and temperature were measured. Histological changes of pancreases and livers were observed microscopically. The mRNA expressions of TLR2, 4 were detected by real-time polymerase chain reaction (PCR). The protein expressions of TLR2, 4 were examined by Western blot. RESULTS: Marked edema, inflammatory cell infiltration, hemorrhage, and necrosis were observed in the pancreases and livers of SIRS mice. The concentrations of amylase and glutamic pyruvic transaminase were increased significantly. Body temperature and white blood cell count were decreased. The mRNA and protein expressions of TLR2, 4 increased markedly in SIRS mice. Significant difference was observed between SIRS and control mice (P<0.01). CONCLUSION: The expressions of TLR2, 4 of livers were increased markedly in SIRS mice, indicating that TLR might play an important role in the pathogenesis of SIRS.
BACKGROUND: Toll-like receptor (TLR) 2/4 might play important roles in mediating proinflammatory cytokine synthesis and release. And nitric oxide (NO) has been used to treat acute respiratory distress syndrome (ARDS). This study aimed to investigate the changes in TLR2/4 gene expression in the lungs of rats with acute lung injury (ALI) complicated by acute hemorrhage necrotizing pancreatitis (AHNP) and the effect of NO on the TLR2/4 gene expression. METHODS: One hundred and ten SD male rats were randomly divided into sham-operated group ( n = 10) , AHNP group (n = 30) , chloroquine-treated group ( n = 30) , and L-Arg-treated group (n =40). The lungs were dissected for lung histological scoring, and bronchoalveolar lavages were harvested for lung injury indexing. TLR2/4 mRNA expression in the lungs was measured by RT-PCR. RESULTS: TLR2/4mRNA was detected in the lungs with low values in the sham-operated group (0.016±0. 210E-2, 0.112 ±0.750E-2) , but it was markedly increased at 3 hours in the AHNP group (0.787±0.751E-2, 1.512 ±1.794E-2) , peaking at 12 hours (1.113 ±6.141E-2, 2.957±2.620E-2; P <0.05 or P <0.01). When lung injuries were aggravated, TNF-α concentrations in the lungs were increased, but NO concentrations were decreased ( P < 0.05 or P < 0.01 ) . When TLR2/4mRNA was inhibited by CQ (3h: 0.313 ± 5.491E-2, 0.005 ±1.419E-3 ; 6h: 0.488 ±7.442E-2, 0.010 ± 1.518E-3; 12h: 0.883 ± 8.911E-2, 0.024 ± 2.760E-3; P< 0.05 or P <0.01) , lung injuries were relieved. NO concentrations in the lungs were increased but TNF-α concentrations were decreased (P <0. 05 or P <0.01). When the rats with AHNP were treated with L-Arg, TLR2/4mRNA expression in the lungs could be effectively inhibited (50mg-T: 0.656 ±3. 977E-2, 1. 501 ±6.111E-2; 100mg-T: 0.260± 0.891E-2, 0.732 ±5.135E-2; 200mg-T: 0.126 ±0.914E-2, 0.414 ± 1.678E-2; 400mg-T: 0.091 ±0.399E-2, 0.287 ± 0.176E-2; P <0.05 or P <0. 01) and lung injuries were relieved. At the same time, NO concentrations in the lungs were markedly increased, but TNF-α
He-Shui Wu, Lei Zhang, Yan Chen, Xing-Jun Guo, Lin Wang, Jian-Bo Xu, Chun-You Wang and Jing-Hui Zhang Center of Pancreatic Surgery Laboratory of General Surgery Affiliated Union Hospital of Tongji Medical College, Hua-zhong University of Science and Technology, Wuhan 430022, China
