Celastrol alleviates sepsis-induced acute lung injury in rats by inhibiting the Toll-like receptor 4/nuclear factor-κB inflammatory pathway / 中华危重病急救医学

ABSTRACT

Objective:To investigate the protective effect and mechanism of celastrol in acute lung injury (ALI) of septic rats.Methods:According to random number table, 24 male Sprague-Dawley (SD) rats were divided into control group (Con group), Sham operation group (Sham group), sepsis-induced ALI group by cecal ligation and perforation (CLP group) and celastrol intervention group (CLP+celastrol group, 2 mg/kg intraperitoneal administration 1 hour before surgery), 6 rats in each group. The abdominal aortic blood of the rats was collected for blood gas analysis 24 hours after the surgery, and then the rats were sacrificed and the lung tissues were taken to calculate the lung wet/dry weight ratio (W/D). The pathological characteristics of lung tissues were observed under light microscope and calculated the lung injury score. The protein levels of Toll-like receptor 4 (TLR4), interleukins (IL-6, IL-10), and nuclear factor-κB (NF-κB) of cytoplasm and nucleus in lung tissues were detected by enzyme linked immunosorbent assay (ELISA).Results:The partial arterial oxygen pressure (PaO 2), lung W/D ratio, lung injury score and the protein levels of inflammatory factor in lung tissues had no differences between Con group and Sham group. Compared with the Con group, PaO 2 in the CLP group was significantly decreased [mmHg (1 mmHg = 0.133 kPa) 60.33±2.01 vs. 109.20±2.99], the lung W/D ratio and lung injury score were significantly increased (lung W/D ratio 4.44±0.05 vs. 3.27±0.04, lung injury score 10.67±0.42 vs. 0.50±0.22), and the protein levels of TLR4, IL-6, IL-10 and the nucleus NF-κB in the lung tissues were significantly increased [TLR4 (pg/L) 21.87±0.66 vs. 3.27±0.09, IL-6 (ng/L) 861.10±8.28 vs. 120.30±3.91, IL-10 (ng/L) 212.40±2.57 vs. 41.73±1.02, nuclear NF-κB (ng/L) 707.70±16.82 vs. 403.30±7.46], but the protein level of cytoplasm NF-κB was significantly decreased (ng/L 213.70±8.67 vs. 408.30±8.71), with statistically significant differences (all P < 0.05). Compared with the CLP group, PaO 2 in CLP+celastrol group was significantly increased (mmHg 76.83±3.21 vs. 60.33±2.01), the lung W/D ratio and lung injury score were significantly decreased (lung W/D ratio 3.82±0.03 vs. 4.44±0.05, lung injury score 5.00±0.37 vs. 10.67±0.42), and the protein levels of TLR4, IL-6, IL-10 and nucleus NF-κB in the lung tissue were significantly decreased [TLR4 (pg/L) 7.57±0.21 vs. 21.87±0.66, IL-6 (ng/L) 380.90±6.55 vs. 861.10±8.28, nuclear NF-κB (ng/L) 533.80±9.42 vs. 707.70±16.82], and the protein level of cytoplasm NF-κB was significantly increased (ng/L 342.70±14.96 vs. 213.70±8.67), with statistically significant differences (all P < 0.05), while the protein level of IL-10 in lung tissues had no significant difference (ng/L 210.50±3.16 vs. 212.40±2.57, P > 0.05). Conclusion:Celastrol may regulate the expression and release of inflammatory factors by inhibiting the TLR4/NF-κB pathway, thereby alleviating the ALI induced by sepsis in rats.