To explore the effect of Smad4 on the extracellular matrix remodeling in ventilatorinduced lung injury (VILI).Methods.
We randomized 24 C57BL/6 mice to 4 groups for treatment (n=6/group): control, ventilation, non-targeted (scramble) lentivirus transfection plus ventilation, and Smad4 small interfering RNA (siRNA) lentivirus transfection plus ventilation. Lentivirus was delivered by intranasal instillation. Four weeks later, the 3 ventilated groups underwent high tidal volume (VT 40mL/kg) ventilation to induce lung injury. After 72 hours, lungs were collected from the anesthetized live mice. Histological changes in lungs were evaluated by hematoxylin and eosin and Masson's staining. The expression of α-smooth muscle actin (α-SMA) was determined by immunohistochemistry, and the mRNA and protein levels of Smad4, α-SMA, and collagen I and III were detected by quantitative real-time PCR and western blotting analysis.Results.
Smad4 siRNAs significantly knocked down Smad4 expression (P<.05), which was increased with ventilation, thereby alleviating inflammatory cell infiltration. It also inhibited accumulation of α-SMA-positive myofibroblasts and pulmonary fibrosis, as seen by reduced collagen I and III expression (P<.05), induced by ventilation. Scramble siRNA treatment had no effect (P>.05).Conclusion.
Smad4 gene silencing may be a therapeutic target for treating ventilator-induced lung injury and pulmonary fibrosis.