Role of syndecan-4 in inflammatory responses of rats with ventilator-induced lung injury

Abstract

Objective To evaluate the role of syndecan-4(SDC-4)in inflammatory responses of rats with ventilator-induced lung injury(VILI). Methods Twenty-four healthy male wild type Sprague-Dawley rats and 24 male SDC-4 gene knockout Sprague-Dawley rats, aged 2-3 months, weighing 200-220 g, were assigned into 2 groups(n=12 each)using a random number table: control group(group C)and VILI group.The animals were anesthetized with pentobarbital sodium and tracheostomized.The rats kept spontaneous breathing in group C. The rats were mechanically ventilated for 4 h in group VILI.Blood samples were taken from the femoral artery at the end of mechanical ventilation for detection of arterial oxygen partial pressure(PaO2). The animals were sacrificed after blood sampling.The left lung was lavaged, and the broncho-alveolar lavage fluid(BALF)was collected for determination of the tumor necrosis factor-α(TNF-α), interleukin-1beta(IL-1β)and IL-18 concentrations(by enzyme-linked immunosorbent assay)and total protein concentrations(by BCA assay). The right lungs were removed for determination of the wet to dry weight ratio(W/D ratio)and expression of TNF-α, IL-1β and IL-18 mRNA in lung tissues(by real-time polymerase chain reaction)and for examination of the pathological changes(with a light microscope). The lung injury scores were recorded. Results Compared with group C of wild type rats, PaO2 was significantly decreased, W/D ratio and lung injury scores were increased, the concentrations of total protein, TNF-α, IL-1β and IL-18 in BALF were increased, and the expression of TNF-α, IL-1β and IL-18 mRNA in lung tissues was up-regulated in group VILI of wild type rats(P 0.05). Compared with group C of gene knockout rats, PaO2 was significantly decreased, W/D ratio and lung injury scores were increased, the concentrations of total protein, TNF-α, IL-1β and IL-18 in BALF were increased, and the expression of TNF-α, IL-1β and IL-18 mRNA in lung tissues was up-regulated in group VILI of gene knockout rats(P<0.05). Compared with group VILI of wild type rats, PaO2 was significantly decreased, W/D ratio and lung injury scores were increased, the concentrations of total protein, TNF-α, IL-1β and IL-18 in BALF were increased, and the expression of TNF-α, IL-1β and IL-18 mRNA in lung tissues was up-regulated in group VILI of gene knockout rats(P<0.05). Conclusion SDC-4 can inhibit inflammatory responses of rats with VILI and is involved in the endogenous protective mechanism. Key words: Syndecan-4; Respiration, artificial; Respiratory distress syndrome, adult; Inflammation