Nebulized Non-Immunogenic Staphylokinase in the Mice Acute Lung Injury Model
Abstract
:1. Introduction
2. Results
2.1. Effect of Inhaled nSta on Coagulation Parameters
2.2. Mice ALI Model and Morphological Examination
2.3. Histological Examination
2.4. Assessment of Fibrin/Fibrinogen Deposition in the Lungs
2.5. Evaluation of the Cytokine Profile by Flow Cytometry
3. Discussion
4. Material and Methods
4.1. Animals
4.2. Evaluation of Coagulation Parameters in Healthy Rats
- Control intact (n = 10): saline nebulization;
- nSta 0.2 mg/kg (n = 10): nSta nebulization at a dose of 0.2 mg/kg;
- nSta 1.0 mg/kg (n = 10): nSta nebulization at a dose of 1.0 mg/kg;
- nSta 2.0 mg/kg (n = 10): nSta nebulization at a dose of 2.0 mg/kg.
4.3. Acute Lung Injury (ALI) Modeling
4.4. ALI Experimental Groups
- Animals were randomly assigned into 6 experimental groups:
- Control nSta (n = 10): nSta nebulization at a dose of 0.2 mg/kg;
- Control intact (n = 10): saline nebulization;
- ALI (n = 10): saline nebulization;
- nSta (n = 10): nSta nebulization at a dose of 0.2 mg/kg;
- nSta (n = 10): nSta nebulization at a dose of 0.4 mg/kg;
- nSta (n = 10): nSta nebulization at a dose of 0.6 mg/kg.
4.5. Necropsy
4.6. Histological Examination
4.7. Assessment of Fibrin/Fibrinogen Deposits in the Lungs
4.8. Evaluation of the Cytokine Profile by Flow Cytometry
4.9. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Groups | Fibrinogen, g/L (M ± SD) | APTT, s (M ± SD) | Prothrombin Time, s (M ± SD) | |||
---|---|---|---|---|---|---|
Day 7 | Day 21 | Day 7 | Day 21 | Day 7 | Day 21 | |
Control intact (n = 10) | 1.96 ± 0.10 | 1.91 ± 0.13 | 15.26 ± 062 | 15.36 ± 0.63 | 22.44 ± 0.85 | 22.18 ± 0.58 |
nSta 0.2 mg/kg (n = 10) | 1.91 ± 0.09 | 1.93 ± 0.09 | 15.14 ± 0.65 | 15.40 ± 0.46 | 22.34 ± 0.74 | 22.12 ± 0.45 |
nSta 1.0 mg/kg (n = 10) | 1.93 ± 0.08 | 1.96 ± 0.09 | 15.24 ± 0.34 | 15.18 ± 0.55 | 22.20 ± 0.83 | 22.16 ± 0.71 |
nSta 2.0 mg/kg (n = 10) | 1.92 ± 0.10 | 1.94 ± 0.13 | 15.32 ± 0.66 | 15.12 ± 0.56 | 22.20 ± 0.80 | 22.24 ± 0.83 |
Groups | Weight before ALI Induction, g (M ± SD) | Weight on Day 8, g (M ± SD) |
---|---|---|
Control nSta (n = 10) | 19.56 ± 0.14 | 26.31 ± 0.95 |
Control intact (n = 10) | 18.44 ± 0.75 | 27.12 ± 0.63 |
ALI (n = 6) | 19.87 ± 0.25 | 21.20 ± 0.75 * |
ALI + nSta 0.2 mg/kg (n = 10) | 19.26 ± 0.32 | 23.54 ± 0.24 |
ALI + nSta 0.4 mg/kg (n = 10) | 18.63 ± 0.27 | 25.37 ± 0.59 |
ALI + nSta 0.6 mg/kg (n = 10) | 18.92 ± 0.31 | 26.63 ± 0.10 |
Groups | Lungs’ Weight, g (M ± SD) | Exudate Score in Lungs (M ± SD) | Interstitial Edema and Hyaline Membrane Formation Score in Lungs (M ± SD) |
---|---|---|---|
Control nSta (n = 10) | 0.165 ± 0.011 | 0 | 1 |
Control intact (n = 10) | 0.161 ± 0.028 | 0 | 1 |
ALI (n = 6) | 0.233 ± 0.013 * | 2.33 ±0.51 ** | 3.66 ± 0.51 ** |
ALI + nSta 0.2 mg/kg (n = 10) | 0.191 ± 0.014 ^ | 1.1 ± 0.73 | 2.2 ± 0.78 |
ALI + nSta 0.4 mg/kg (n = 10) | 0.187 ± 0.024 ^ | 0.6 ± 0.51 ^^ | 1.4 ± 0.51 ^ |
ALI + nSta 0.6 mg/kg (n = 10) | 0.161 ± 0.008 ^^ | 0.5 ± 0.52 ^^ | 1 ^^ |
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Markin, S.S.; Lapshin, R.D.; Baskina, O.S.; Korotchenko, S.A.; Mukhina, I.V.; Ivanov, S.V.; Semenov, M.P.; Beregovykh, V.V.; Semenov, A.M. Nebulized Non-Immunogenic Staphylokinase in the Mice Acute Lung Injury Model. Int. J. Mol. Sci. 2022, 23, 9307. https://doi.org/10.3390/ijms23169307
Markin SS, Lapshin RD, Baskina OS, Korotchenko SA, Mukhina IV, Ivanov SV, Semenov MP, Beregovykh VV, Semenov AM. Nebulized Non-Immunogenic Staphylokinase in the Mice Acute Lung Injury Model. International Journal of Molecular Sciences. 2022; 23(16):9307. https://doi.org/10.3390/ijms23169307
Chicago/Turabian StyleMarkin, Sergey S., Roman D. Lapshin, Olga S. Baskina, Svetlana A. Korotchenko, Irina V. Mukhina, Sergei V. Ivanov, Mikhail P. Semenov, Valerii V. Beregovykh, and Andrey M. Semenov. 2022. "Nebulized Non-Immunogenic Staphylokinase in the Mice Acute Lung Injury Model" International Journal of Molecular Sciences 23, no. 16: 9307. https://doi.org/10.3390/ijms23169307