To investigate the effect of intratracheal injection of c-Jun N-terminal kinase (JNK) siRNA plasmid on ischemia-reperfusion (I/R) injury in a rat model of lung transplantation.

ExperimentⅠ Thirty-two male Wistar rats, weighing 250-280 g, were divided into 2 groups (n=16 each) using a random number table method: control group (group C) and JNK siRNA group.JNK siRNA plasmid 2 mg/kg (diluted to 0.2 ml in sterile phosphate buffer solution) was intratracheally injected in JNK siRNA group.Scrambled siRNA plasmid 2 mg/kg (diluted to 0.2 ml in sterile phosphate buffer solution) was intratracheally injected in group C. Six rats in each group were sacrificed at 48 h of administration, and left lung tissues were removed for determination of the expression of JNK and JNK mRNA (by Western blot and real-time polymerase chain reaction, respectively). The other 10 rats left in each group were used for left lung transplantation.Experiment Ⅱ Thirty male Wistar rats, weighing 250-280 g, were divided into 3 groups (n=10 each) using a random number table method: sham operation group (group S), transplanted lung I/R group (group I/R) and transplanted lung I/R+ JNK siRNA group (group I/R+ JNK siRNA). In group I/R and group I/R+ JNK siRNA, the left lung transplantation was performed, and the donor lungs were obtained from the living donors in group C and group JNK siRNA, respectively.At 15 min of mechanical ventilation and 30, 60, 90 and 120 min of reperfusion, arterial blood samples were obtained for blood gas analysis, PaO₂ was recorded, and the oxygenation index (PaO₂÷FiO₂) was calculated.Arterial blood samples were obtained at 120 min of reperfusion in transplanted lungs for determination of concentrations of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and interferon-γ (IFN-γ) in serum (using enzyme-linked immunosorbent assay), and the rats were sacrificed and left lung tissues were removed for microscopic examination of the pathological changes which were scored and for determination of wet/dry lung weight ratio (W/D ratio), and nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) activities (using enzyme-linked immunosorbent assay).

ExperimentⅠ Compared with group C, the expression of JNK and JNK mRNA was significantly down-regulated in group JNK siRNA (P<0.05). ExperimentⅡ Compared with group S, the oxygenation index was significantly decreased, and the concentrations of serum IL-8, TNF-α and IFN-γ, W/D ratio, lung injury score and activities of NF-κB and AP-1 were increased in I/R and I/R+ JNK siRNA groups (P<0.05). Compared with group I/R, the oxygenation index of receptors were significantly increased, and the concentrations of serum IL-8, TNF-α and IFN-γ, W/D ratio, lung injury score and activities of NF-κB and AP-1 were decreased in group I/R+ JNK siRNA (P<0.05).

Intratracheal injection of JNK siRNA can reduce transplanted lung I/R injury, and the mechanism may be related to inhibiting inflammatory responses of rats.

JNK mitogen-activated protein kinases; Lung transplantation; Reperfusion injury; Injection, intratracheal