Effects of PCSK-9 Inhibition by Alirocumab Treatments on Biliary Cirrhotic Rats
Abstract
:1. Introduction
2. Results
2.1. Mortality Rates of Alirocumab- and Vehicle-Treated Rats
2.2. Body Weight and Hemodynamic Parameters
2.3. The Biochemistry Parameters and Ox-LDL
2.4. Motor Activity of BDL Rats with or without Alirocumab Treatment
2.5. Histopathological Change, Intrahepatic Angiogenesis and Free Cholesterol Accumulation of Liver
2.6. Portal-Systemic Shunting Degree and Mesenteric Vascular Density in BDL Rats with or without Alirocumab Treatment
2.7. Effects of Alirocumab Treatment on Systemic Oxidative Stress
2.8. Hepatic Protein Expressions in the Liver of BDL Rats
3. Discussion
4. Materials and Methods
4.1. Animal Model for Biliary Cirrhosis
4.2. Study Protocol
4.3. Measurement of Systemic and Portal Hemodynamics
4.4. Measurement of Motor Activities
4.5. Hepatic Histopathological Examination, Free Cholesterol Accumulation and Fibrosis Determination
4.6. Intrahepatic Angiogenesis Evaluation with CD31 Immunohistochemical Staining
4.7. Determination of Portal-Systemic Collateral Shunting Degree
4.8. Determination of the Mesenteric Vascular Density
4.9. Determination of Systemic Lipid Peroxidation and Antioxidant Capacity
4.10. Western Blot Analysis
4.11. Drugs
4.12. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
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Sham + Alirocumab (n = 12) | Sham + Vehicle (n = 8) | BDL + Alirocumab (n = 12) | BDL + Vehicle (n = 11) | |
---|---|---|---|---|
BW (g) | 429 ± 26 | 420 ± 38 | 374 ± 23 * | 384 ± 36 * |
MAP (mmHg) | 155 ± 9 | 145 ± 10 | 134 ± 14 * | 132 ± 14 * |
PP (mmHg) | 8.6 ± 1.0 | 8.7 ± 0.8 | 16.4 ± 1.9 * | 16.9 ± 2.6 * |
HR (beats/min) | 404 ± 37 | 394 ± 48 | 390 ± 34 | 401 ± 30 |
PVf (mL/min/100 g) | 8.9 ± 1.3 | 10.1 ± 0.9 | 12.9 ± 2.1 * | 11.7 ± 1.7 * |
SMAf (mL/min/100 g) | 6.2 ± 1.0 | 5.8 ± 0.6 | 8.4 ± 1.1 * | 8.2 ± 1.6 * |
SMAR (mmHg/mL/min/100 g) | 24.2 ± 3.7 | 23.8 ± 2.8 | 14.3 ± 2.9 * | 14.7 ± 4.1 * |
SVR (mmHg/mL/min/100 g) | 4.8 ± 0.7 | 5.1 ± 0.7 | 3.2 ± 0.5 * | 3.1 ± 0.7 * |
CI (mL/min/100 g) | 33.4 ± 5.0 | 28.7 ± 2.9 | 43.0 ± 6.4 * | 44.1 ± 7.4 * |
Sham + Alirocumab (n = 12) | Sham + Vehicle (n = 8) | BDL + Alirocumab (n = 12) | BDL + Vehicle (n = 11) | |
---|---|---|---|---|
TC (mg/dL) | 35 ± 11 a | 52 ± 12 | 62 ± 14 b | 81 ± 9 c |
LDL (mg/dL) | 7 ± 4 a | 11 ± 2 | 31 ± 9 b | 45 ± 9 c |
Ox-LDL (ng/mL) | 39 ± 5 | 44 ± 10 | 757 ± 183 | 714 ± 237 c |
Ammonia (μmol/L) | 97 ± 11 | 106 ± 26 | 249 ± 86 | 235 ± 66 c |
ALT (IU/L) | 45 ± 10 | 55 ± 12 | 115 ± 28 | 118 ± 37 c |
AST (IU/L) | 110 ± 47 | 101 ± 51 | 620 ± 174 | 567 ± 132 c |
TB (mg/dL) | 0.03 ± 0.01 | 0.04 ± 0.03 | 8.3 ± 1.1 | 8.4 ± 1.3 c |
Cr (mg/dL) | 0.36 ± 0.09 | 0.41 ± 0.08 | 0.44 ± 0.08 | 0.44 ± 0.11 |
BDL + Vehicle (n = 11) | BDL + Alirocumab (n = 12) | |
---|---|---|
Distance traveled (cm) | 14,608 ± 4497 | 16,991 ± 5963 |
Resting time (s) | 897 ± 230 | 802 ± 324 |
Ambulatory time (s) | 758 ± 185 | 853 ± 299 |
Stereotypic time (s) | 127 ± 47 | 123 ± 40 |
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Huang, H.-C.; Hsu, S.-J.; Chang, C.-C.; Chuang, C.-L.; Hou, M.-C.; Lee, F.-Y. Effects of PCSK-9 Inhibition by Alirocumab Treatments on Biliary Cirrhotic Rats. Int. J. Mol. Sci. 2022, 23, 7378. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137378
Huang H-C, Hsu S-J, Chang C-C, Chuang C-L, Hou M-C, Lee F-Y. Effects of PCSK-9 Inhibition by Alirocumab Treatments on Biliary Cirrhotic Rats. International Journal of Molecular Sciences. 2022; 23(13):7378. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137378
Chicago/Turabian StyleHuang, Hui-Chun, Shao-Jung Hsu, Ching-Chih Chang, Chiao-Lin Chuang, Ming-Chih Hou, and Fa-Yauh Lee. 2022. "Effects of PCSK-9 Inhibition by Alirocumab Treatments on Biliary Cirrhotic Rats" International Journal of Molecular Sciences 23, no. 13: 7378. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137378