Int J Clin Exp Patho
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Int J Clin Exp Patho · Jan 2015
Blocking HMGB1 signal pathway protects early radiation-induced lung injury.
It has been reported that HMGB1 participated in various types of lung injury. In this study, we explored whether blocking HMGB1 has a preventive effect on the early radiation-induced lung injury and investigate the mechanism. Mice model of radiation-induced lung injury were accomplished by a single dose irradiation (15 Gy) to the whole thorax. ⋯ In addition, HMGB1 antagonist can restrain the expression of type Th2 or Th17 derived inflammatory cytokines TNF-α, IL-6 and IL-17A, promote the expression of Th1 type cytokines INF-γ, and inhibit p65 NF-κB but promote p50 NF-κB activation, which promoted the resolution of the radiation-induced inflammatory response. In conclusion, blocking HMGB1 can reduce the degree of early radiation-induced lung injury, and its mechanism may be related to the promotion of p50NF-κB activation and its downstream molecules expression. Inhibiting HMGB1 may be a new target to deal with early radiation-induced lung injury.
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Int J Clin Exp Patho · Jan 2015
Ethyl pyruvate reduces hepatic mitochondrial swelling and dysfunction in a rat model of sepsis.
Sepsis causes mitochondrial oxidative injury and swelling. Ethyl pyruvate (EP) is a cytoprotective agent, while aquaporin-8 (AQP8) is a mitochondrial water channel that can induce mitochondrial swelling. We assessed whether EP protects mitochondria during sepsis, and whether AQP8 contributes to the underlying mechanisms. ⋯ Mitochondrial Cyt C release was higher in the CLP group than in the sham (1.211±0.24 vs. 0.48±0.03) or CLP+EP (0.35±0.39) groups. AQP8 expression was similar between groups, with a trend for lower expression in the CLP+EP group compared with the CLP group. EP improves sepsis outcome by targeting the mitochondrion, possibly through modulation of AQP8 expression.
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Int J Clin Exp Patho · Jan 2015
Ruscogenin exerts beneficial effects on monocrotaline-induced pulmonary hypertension by inhibiting NF-κB expression.
This study aims to examine the effect of ruscogenin on pulmonary arterial hypertension (PAH) and to determine the mechanism underlying this effect. We isolated pulmonary vascular smooth muscle cells (PVSMCs) from the pulmonary artery of the rats; the PVSMCs were cultured in vitro and then were treated with platelet-derived growth factor (PDGF), PDGF + ruscogenin, or PDGF + ruscogenin + parthenolide. We randomized Sprague-Dawley rats into five groups as follows: control group, PAH group, low-dose group, medium-dose group, and high-dose group; the rats in the low-, medium-, and high-dose groups received the vehicle and ruscogenin 0.1, 0.4, and 0.7 mg/kg, respectively, from day 1 to day 21 after injection of monocrotaline (MCT). ⋯ We examined the levels of the nuclear factor kappa B (NF-κB) protein by using immunohistochemistry and western blot analysis, and the mRNA levels of NF-κB in PVSMCs were evaluated using real-time polymerase chain reaction (PCR). The mPAP, RVSP, and PAWT and the protein and mRNA levels of NF-κB were significantly higher in the PAH model group than in the control group (P < 0.05). Ruscogenin induced a significant dose-dependent decrease in the mPAP, RVSP, and PAWT and in the NF-κB expression in the PAH group (P < 0.05), which suggests that ruscogenin will also exert dose-dependent effects on MCT-induced PAH through the inhibition of NF-κB.
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Int J Clin Exp Patho · Jan 2015
Resveratrol attenuates spinal cord injury-induced inflammatory damage in rat lungs.
Spinal cord injury (SCI)-induced systemic inflammatory response affects multiple organs outside the spinal cord. Treatment options for such complications are lacking. We studied the potential protective effects of resveratrol on SCI-induced inflammatory damage in rat lungs. ⋯ Resveratrol significantly reduced neutrophil infiltration and production of inflammatory mediators. Resveratrol treatment was accompanied by up-regulation of expression of SIRT1 and suppression of NF-κB activity in pulmonary tissues. These data suggest that resveratrol may protect the lungs from SCI-induced inflammatory damage, and could be used as a therapeutic option against pulmonary problems after SCI.
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Int J Clin Exp Patho · Jan 2014
Expression analysis of BMP2, BMP5, BMP10 in human colon tissues from Hirschsprung disease patients.
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor β (TGF β) superfamily. BMP2, BMP5 and BMP10 exert their biological functions by interacting with membrane bound receptors belonging to the serine/threonine kinase family. Hirschsprung disease (HSCR) is characterized by the absence of intramural ganglion cells in the nerve plexuses of the distal gut. However, putative Notch function in enteric nervous system (ENS) development and the etiology of HSCR is unknown. ⋯ BMP2, BMP5 and BMP10 are elevated in the stenotic colon segment of HSCR, and BMPs signaling plays a pivotal role in the development of HSCR.