To investigate the effect of lidocaine on lung injury and expression of inflammatory factors in septic rats.

Sixty male adult Sprague Dawley rats were randomly divided into the sham operation group, cecal ligation and puncture (CLP) group, ulinastatin group and lidocaine group, with 15 rats in each group. The abdominal cavity of rats was opened and sutured in the sham operation group, and sepsis models in the other groups were established by the CLP method. Rats in the lidocaine group were continuously pumped with lidocaine through the tail vein at a dose of 10 mg·kg^-1·h^-1 for 3 h after injecting a loading dose of 10 mg/kg. Rats in the ulinastatin group were given CLP and continuously pumped with ulinastatin through the tail vein at a dose of 100 000 U·kg^-1·h^-1 for 3 h. Rats in the sham operation and CLP groups were injected with equal amount of isoosmotic NaCl solution. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1) in serum were determined by enzyme-linked immunosorbent assay (ELISA), as all rats were sacrificed at 24 h after CLP. The expression of HMGB1 mRNA in lung tissue was detected by real-time fluorescence quantitative PCR, and the pathological changes of lung tissue in each group were observed by hematoxylin-eosin (HE) staining. Another 40 rats (10 in each group) were used to observe the death condition at 72 h in 4 groups.

The levels of TNF-α, IL-6, HMGB1, and HMGB1 mRNA in serum of the four groups were significantly different (F=189.886, 237.952, 175.999, 179.491; all P < 0.001). Further pairwise comparison showed that the levels of serum TNF-α, IL-6, HMGB1, and HMGB1 mRNA in the CLP, lidocaine and ulinastatin groups were significantly higher than those in the sham operation group (all P < 0.05). Compared with the CLP group, the levels of TNF-α, IL-6, HMGB1, and HMGB1 mRNA were significantly lower in the lidocaine and ulinastatin groups (all P < 0.05). Compared with the lidocaine group, the IL-6 level was significantly higher in the ulinastatin group (P < 0.05). The HE staining showed uniform alveoli with intact structure and normal alveolar epithelial cells of rats in the sham operation group. Alveolar septum thickening, interstitial congestion and edema, inflammatory cell infiltration and alveolar collapse were found in the CLP group. However, the pathological changes in the lidocaine and ulinastatin groups were significantly less than those in the CLP group; the lung tissue was mildly edematous, and a small amount of inflammation appeared in alveoli and pulmonary stroma. The proportional mortality indicator (0/10, 9/1, 4/6, 3/7) was significantly different among the four groups (χ²=17.500, P < 0.001). It was significantly higher in the CLP, lidocaine and ulinastatin groups than in the sham operation group (all P < 0.008). It was significantly lower in the lidocaine and ulinastatin groups than in the CLP group (both P < 0.008), and there was no significant difference in the proportional mortality indicator between the lidocaine and ulinastatin groups (P > 0.008).

By reducing the expressions of TNF-α, IL-6 and HMGB1 and inhibiting the HMGB1 mRNA expression in lung tissue, continuous intravenous injection of lidocaine can alleviate pulmonary injury induced by sepsis and effectively improve the survival rate. The effect of lidocaine on inflammatory reaction and lung protection after sepsis is similar to that of ulinastatin.