Effect and mechanism of carbazochrome sodium sulfonate in reducing acute lung injury in rats with sepsis

Abstract

Objective　To explore the effect and mechanism of carbazochrome sodium sulfonate on acute lung injury in septic rats. Methods　Healthy male Wistar rats were randomized into 5 groups: sham group (n=25), sepsis group (n=25), low dose group (carbazochrome sodium sulfonate: 8 mg/kg)(n=25), middle dose group (carbazochrome sodium sulfonate: 40 mg/kg)(n=25), and high dose group (carbazochrome sodium sulfonate: 80 mg/kg)(n=25). Two additional groups, the autophagy inhibition group (3-MA)(n=10) and the sepsis middle dose group (carbazochrome sodium sulfonate: 40 mg/kg)(n=10), are also included in this study. After the preparation of septic rats by cecal ligation and puncture, the different doses of carbazochrome sodium sulfonate or 3-MA were given by intraperitoneal injection. The survival curve is drawn. After CLP 24 hours, the lung Micro-CT of those survival rats were examined. The arterial blood gas, pulmonary index and vascular permeability of lung tissue were measured. Pathological changes of lung tissues were observed by HE staining. The level of autophagic marker (LC3-Ⅱ/LC3-Ⅰ) of lung tissue was measured by Western blotting. Results　Compared with sepsis group, the survival rate of the rats of carbazochrome sodium sulfonate groups increased, the arterial blood oxygen partial pressure and oxygenation index increased, the pulmonary index and vascular permeability decreased, and the differences were statistically significant (P<0.05). Both lung Micro-CT and HE staining showed that the lung lesions were more serious in sepsis group, while carbazochrome sodium sulfonate alleviated these lesions. Western blotting results showed that, the ratio of LC3-Ⅱ/LC3-Ⅰ in lung tissue of septic rats was higher than sham group (5.1±2.7 vs. 2.7±0.7, P<0.05), while the ratio of LC3-Ⅱ/LC3-Ⅰ in lung tissue in the low dose and middle dose carbazochrome sodium sulfonate groups was further increased than sepsis group (6.8±2.6, 8.9±1.4 vs. 5.1±2.7, both P<0.05). The value of LC3-Ⅱ/LC3-Ⅰ in the lung tissue of rats in 3-MA group was significantly lower than that in the middle dose carbazochrome sodium group (3.1±1.7 vs. 8.7±1.6), and the difference was statistically significant (P<0.05). Conclusion　The mechanism by which carbazochrome sodium sulfonatealleviating lung injury is related to the up-regulation of autophagy level in septic rats.