摘要Objective: To investigate the protective effect of cobra venom factor(CVF) on lung tissue injury in rats with sepsis induced by cecal puncture, with a view to providing theoretical basis for the development of new anti-sepsis drugs. Methods: A total of 144 rats were randomly divided into sham operation group, sepsis group and CVF group, with 48 rats in each group. Cecal ligation and puncture(CLP) was used to establish a rat model of sepsis. And 8 rats were taken from each group at 2, 4, 8, 12, 16 and 24 h to observe the differences in lung wet/dry weight ratio, lung histopathological changes, and serum inflammatory factor levels. Results: CVF treatment significantly alleviated the degree of pulmonary edema and swelling in septic rats, slowed down the trend of elevated lung wet/dry weight ratio, and reduced the pathological damage of lungs. The degree of vascular congestion, edema and inflammatory cell infiltration in lung tissue of the sepsis group increased with time, and the degree of lesions in the CVF group was milder than that in the sepsis group. The TNF-α level in lung tissue of septic rats was significantly down-regulated by CVF treatment, and the TNF-α levels in the CVF group during the 8-24 h period ranged from [8 h:(1.47±0.14) ng/ml] to [24 h:(1.14±0.03) ng/ml], which was closer to that in sham operation group. Meanwhile, the IL-10 level decreased from (91.3±5.5) ng/L to (39.8±13.4) ng/L during 8-24 h, which was higher than other groups. Conclusion: CVF can play a protective role against injury by down-regulating TNF-α and up-regulating IL-10 pathways, which can serve to alleviate focal lung injury and pulmonary edema from sepsis.
Abstract：Objective: To investigate the protective effect of cobra venom factor(CVF) on lung tissue injury in rats with sepsis induced by cecal puncture, with a view to providing theoretical basis for the development of new anti-sepsis drugs. Methods: A total of 144 rats were randomly divided into sham operation group, sepsis group and CVF group, with 48 rats in each group. Cecal ligation and puncture(CLP) was used to establish a rat model of sepsis. And 8 rats were taken from each group at 2, 4, 8, 12, 16 and 24 h to observe the differences in lung wet/dry weight ratio, lung histopathological changes, and serum inflammatory factor levels. Results: CVF treatment significantly alleviated the degree of pulmonary edema and swelling in septic rats, slowed down the trend of elevated lung wet/dry weight ratio, and reduced the pathological damage of lungs. The degree of vascular congestion, edema and inflammatory cell infiltration in lung tissue of the sepsis group increased with time, and the degree of lesions in the CVF group was milder than that in the sepsis group. The TNF-α level in lung tissue of septic rats was significantly down-regulated by CVF treatment, and the TNF-α levels in the CVF group during the 8-24 h period ranged from [8 h:(1.47±0.14) ng/ml] to [24 h:(1.14±0.03) ng/ml], which was closer to that in sham operation group. Meanwhile, the IL-10 level decreased from (91.3±5.5) ng/L to (39.8±13.4) ng/L during 8-24 h, which was higher than other groups. Conclusion: CVF can play a protective role against injury by down-regulating TNF-α and up-regulating IL-10 pathways, which can serve to alleviate focal lung injury and pulmonary edema from sepsis.
WEI Qiao, SHENG Ya-qian, LI Guo-ping. Protective Effect of Cobra Venom Factor on Lung Injury Induced by Cecal Puncture in Septic Rats[J]. 中国生物医学工程学报(英文版）, 2023, 32(4): 170-176.
WEI Qiao, SHENG Ya-qian, LI Guo-ping. Protective Effect of Cobra Venom Factor on Lung Injury Induced by Cecal Puncture in Septic Rats. Chinese Journal of Biomedical Engineering, 2023, 32(4): 170-176.
[1] Tian J, Li Y, Mao X, et al.Effects of the PI3K/Akt/HO-1 pathway on autophagy in a sepsis-induced acute lung injury mouse model[J]. Int Immunopharmacol, 2023,124(Pt B):111063. [2] Wang Y, Zhu CL, Li P, et al.The role of G protein-coupled receptor in neutrophil dysfunction during sepsis-induced acute respiratory distress syndrome[J]. Front Immunol, 2023,14:1112196. [3] Chakraborty S, Winkelmann VE, Braumüller S, et al.Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock[J]. Sci Rep, 2021,11(1):2158. [4] Guo RF, Huber-Lang M, Wang X, et al.Protective effects of anti-C5a in sepsis-induced thymocyte apoptosis[J]. J Clin Invest, 2000,106(10):1271-1280. [5] Mannes M, Schmidt CQ, Nilsson B, et al.Complement as driver of systemic inflammation and organ failure in trauma, burn, and sepsis[J]. Semin Immunopathol, 2021,43(6):773-788. [6] Mollnes TE, Huber-Lang M.Complement in sepsis-when science meets clinics[J]. FEBS Lett, 2020,594(16):2621-2632. [7] Rodrigues P, Picco N, Morgan BP, et al.Sepsis target validation for repurposing and combining complement and immune checkpoint inhibition therapeutics[J]. Expert Opin Drug Discov, 2021,16(5):537-551. [8] Bjerkhaug AU, Granslo HN, Cavanagh JP, et al.Dual inhibition of complement C5 and CD14 attenuates inflammation in a cord blood model[J]. Pediatr Res, 2023,94(2):512-519. [9] Wei Qiao, Sheng Yaqian, Ru Songwei, et al.Effect of cobra venom factor in inhibiting complement activation on serum cytokines in septic rats[J]. Medical Innovation of China,2018,15(23):31-35. (魏乔, 盛雅倩, 茹松伟,等. 眼镜蛇毒因子抑制补体激活对脓毒症大鼠血清细胞因子的影响[J]. 中国医学创新,2018,15(23):31-35.) [10] Wei L, Zhang J, Zhang B, et al.Complement C3 participates in the function and mechanism of traumatic brain injury at simulated high altitude[J]. Brain Res, 2020,1726:146423. [11] Huang X, Zhao W, Zhang L, et al.The role of complement activation in rhabdomyolysis-induced acute kidney injury[J]. PLoS One, 2018,13(2):0192361.
