Effect of rapamycin on activity of NLRC4 inflammasomes in rats with ventilator-induced lung injury / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of rapamycin on the activity of NOD-like receptor C4 (NLRC4) inflammasomes in the rats with ventilator-induced lung injury (VILI).Methods:Thirty-six healthy clean-grade male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), VILI group and rapamycin group (group RAPA). In group RAPA, rapamycin 4 mg·kg -1·d -1 was intraperitoneally injected once a day for 3 consecutive days before establishing the model, while the equal volume of normal saline was given instead in group C and group VILI.The patients were mechanically ventilated for 4 h (tidal volume 20 ml/kg, respiratory rate 80 breaths/min, inspiratory/expiratory ratio 1∶1, fraction of inspired oxygen 21%) in VILI and RAPA groups.Blood samples were collected from the femoral artery after the end of ventilation for blood gas analysis and for determination of serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) concentrations (by enzyme-linked immunosorbent assay), and PaO 2 was recorded.The bronchoalveolar lavage fluid (BALF) was collected for determination of the neutrophil count and IL-1β and IL-18 concentrations by enzyme-linked immunosorbent assay.The lung tissues were obtained for examination of the pathological changes (under the light microscope) after HE staining which were scored and for determination of wet to dry weight (W/D) ratio, and expression of mammalian target of rapamycin (mTOR), NLRC4 and caspase-1 (by Western blot) and expression of NLRC4 mRNA (by real-time polymerase chain reaction). Results:Compared with group C, the W/D ratio, lung injury score, neutrophil counts in BALF, and concentrations of IL-1β and IL-18 in serum and BALF were significantly increased, PaO 2 was decreased, and the expression of mTOR, NLRC4, caspase-1 and NLRC4 mRNA was up-regulated in group VILI and group RAPA ( P<0.01). Compared with group VILI, the W/D ratio, lung injury score, neutrophil counts in BALF, and concentrations of IL-1β and IL-18 in serum and BALF were significantly decreased, PaO 2 was increased, and the expression of mTOR, NLRC4, caspase-1 and NLRC4 mRNA was down-regulated in group RAPA ( P<0.05). Conclusion:The mechanism by which rapamycin alleviates VILI may be related to inhibiting activation of mTOR signaling pathway and inhibiting the activity of NLRC4 inflammasomes in rats.