Table 1.
Characteristics of the 14 included animal studies.
| Study (years) | Species (sex; n = experimental/control group) | Weight | Model(method) | Anesthetic | Treatment group(Method to astraddle sides) | Control group | Outcome index (time) | Intergroup differences |
|---|---|---|---|---|---|---|---|---|
| Deng and Lai 2013 | SD rats (Half male and female; 10/10) | 180–220 g | Sublingual vein injection of pituitrin | — | NGR1 (10 mg/kg/day; i.g.) for 4 days before ischemia and 7 days after ischemia | Negative control group, isometric normal saline (i.g.) for 4 days before ischemia and 7 days after ischemiaPositive control group, diltiazem (i.g.) for 4 days before ischemia and 7 days after ischemia | 1. ST-segment and inversion rate of T-wave 2. AST 3. CK 4. CK-MB 5. LDH 6. LDH1 7. Myocardial infarct size 8. Bcl-2 9. Bax | 1. P < 0.01 2. P < 0.05 3. P < 0.05 4. P < 0.05 5. P < 0.05 6. P < 0.05 7. P < 0.05 8. P < 0.01 9. P < 0.01 |
| Han, 2014 | SD rats (male; 6/6) | 240–260 g | Block LAD 30 min after reperfusion | 20%Ulatan (1.25 g/kg) | NGR1 (5 mg/kg/h; i.v.) 20 min before ischemia | Intravenous infusion of the equal volume of normal saline | 1. Venular RBC velocity (%) 2. Albumin leakage (%) 3. Coronary blood flow (%) 4. Myocardial infarct size 5. Heart rat (bpm) 6. LVDP 7. LVSP 8. +dP/dtmax 9. − dP/dtmax 10. MPO 11. ICAM-1 12. CD18 13. Positive percent of TUNEL (%) 14. ATP 15. ADP 16. AMP 17. ADP/ATP 18. AMP/ATP 19. ATPα/GAPDH 20. ATP5D/GAPDH 21. ATPβ/GAPDH 22. ZO-1/GAPDH 23. VE/GAPDH 24. JAM-1/GAPDH 25. Claudin-5/GAPDH 26. Cav-1/GAPDH 27. Cav-3/GAPDH 28.p-Src/Src 29.Src/GAPDH | 1. P < 0.05 2. P < 0.05 3. P < 0.05 4. P < 0.05 5. P > 0.05 6. P > 0.05 7. P < 0.05 8. P < 0.05 9. P < 0.05 10. P < 0.05 11. P < 0.05 12. P < 0.05 13. P < 0.05 14. P < 0.05 15. P > 0.05 16. P > 0.05 17. P < 0.05 18. P < 0.05 19. P > 0.05 20. P < 0.05 21. P > 0.05 22. P < 0.05 23. P < 0.05 24. P < 0.05 25. P < 0.05 26. P < 0.05 27. P < 0.05 28. P < 0.05 29. P > 0.05 |
| Yu et al., 2014 | Wistar rats (male; 13/13) | 220–280 g | Block LAD | 1% Pentobarbital sodium(40 mg/kg) | NGR1 (2.5 mg/kg/day; i.p.)for 4 weeks after ischemia | Intraperitoneal injection of equal volume of saline after ischemia | 1. MVC 2. MVD 3. VEGF 4. bFGF | 1. P < 0.05 2. P < 0.05 3. P < 0.05 4. P < 0.05 |
| He et al., 2014 | SD rats (male; 8/8) | 240–260 g | Block LAD 30 min after reperfusion | 2% Pentobarbital sodium | NGR1 (5mg/kg/h; i.v.) for 30 min before ischemia; 30 min during ischemia; and 90 min after ischemia | Continuous injection of saline (1 ml/h) | 1. AAR/LV 2. Myocardial infarct size/AAR 3.+dP/dtmax 4.− dP/dtmax 5. LVSP 6. LVDP 7. TUNEL-positive 8. Bcl-2/Bax 9. Cleaved caspase-3/procaspase-3 10. ATP 11. AMP 12. P-AMPK/β-actin 13. ATP synthase-α/β-actin 14. ATP synthase-β/β-actin 15. ATP 5D/β-actin 16. ROCK/β-actin 17. P-MYPT1/MYPT1 | 1. P > 0.05 2. P < 0.05 3. P > 0.05 4. P < 0.05 5. P > 0.05 6. P > 0.05 7. P < 0.05 8. P < 0.05 9. P < 0.05 10. P < 0.05 11. P > 0.05 12. P < 0.05 13. P > 0.05 14. P > 0.05 15. P < 0.05 16. P < 0.05 17. P < 0.05 |
| Xia et al., 2015 | SD rats (male; 6/6) | 250–300 g | Block LAD 30 min after reperfusion | Pentobarbital sodium (30 mg/kg) | NGR1 (60 mg/kg; i.g.) for 5 days | No treatment | 1. Myocardial infarct size 2. CK 3. LDH 4. T-SOD 5. MDA 6. IL-1β 7. IL-8 8. TNF-α 9. p-NF-κBP65/NF-κBP65 10. p-IκBα/IκBα 11. VDUP1/GAPDH | 1. P < 0.01 2. P < 0.01 3. P < 0.05 4. P < 0.001 5. P < 0.01 6. P < 0.01 7. P < 0.01 8. P < 0.01 9. P < 0.01 10. P < 0.01 11. P < 0.01 |
| Yu et al., 2016 | SD rats (male; 10/10) | 200–220 g | The isolated Langendorff-perfused rat hearts received ischemia/reperfusion(40 min/60 min) | Urethane | NGR1 (20 μM) for 15 min before the ischemia | No treatment | 1. LVSP 2. Heart rate 3. +dp/dtmax 4. -dp/dt min 5. MDA 6. SOD 7. CAT 8. CK 9. GSH-Px activities 10. P-JNK/JNK 11. CHOP/β-actin 12. Bcl-2/BAX 13. GRP78/β-actin 14. P-PERK/PERK 15. P-eIf2α/eIf2α 16. IRE1/β-actin 17. ATF6/β-actin 18. Caspase-12/β-actin 19. BAX/β-actin | 1. P < 0.01 2. P < 0.05 3. P < 0.01 4. P < 0.01 5. P < 0.01 6. P < 0.01 7. P < 0.01 8. P < 0.001 9. P < 0.001 10. P < 0.001 11. P < 0.001 12. P < 0.001 13. P < 0.01 14. P < 0.001 15. P < 0.001 16. P < 0.001 17. P < 0.01 18. P < 0.001 19. P < 0.001 |
| Meng et al., 2014 | SD rats (male; 40/40) | 250–300 g | MCAO | Ketamine (80 mg/kg; i.p.) | NGR1 (20 mg/kg; i.p) before ischemia | Given the same amount of saline | 1. Infarction volumes 2. Neurologic deficit score 3. TUNEL-positive cells rate 4. Caspase-3 activity 5. NADPH oxidase activity 6. Superoxide levels 7. Mitochondrial superoxide levels 8. MDA 9. Protein carbonyl levels 10. 8-OHdG levels 11. HO-1 activity | 1. P < 0.01 2. P < 0.01 3. P < 0.01 4. P < 0.01 5. P < 0.01 6. P < 0.01 7. P < 0.01 8. P < 0.01 9. P < 0.01 10. P < 0.01 11 . P< 0.01 |
| Dong et al., 2015 | SD rats (male; 8/8) | 180–200 g | MCAO | 10% Chloral hydrate (300 mg/kg; i.p.) | NGR1 (7.0 mg/kg; i.p.) for 14 days after ischemia | Given the same amount of saline | 1. Infarction volumes 2. Neurologic deficit score 3. Population spike 4. Escape latency 5. Target quadrant dwell time | 1. P < 0.01 2. P < 0.01 3. P < 0.01 4. P < 0.01 5. P < 0.01 |
| Wang et al., 2016 | 7-day-old SD rats (male; 5/5) | – | The common carotid artery (CCL) | Isoflurane (2.5%) | NGR1 (15 mg/kg· 12 h; i.p.) after CCL; before exposure to the hypoxic environment | No treatment | 1. Infarction volumes 2. Ratio of GRP78/β-actin 3. Ratio of P-PERK/PERK 4. Ratio of P-IRE1α/IRE1α 5. Ratio of CHOP/β-actin | 1. P < 0.05 2. P < 0.05 3. P < 0.05 4. P < 0.05 5. P < 0.05 |
| Zhao et al., 2017 | SD rats (male; 10/10) | – | MCAO | 3% Pelltobarbitalum Natricum (0.2 ml/100 g) | NGR1 (5 mg/ml; i.v.) for 3 days | Given the same amount of saline | 1. The number of TUNEL-positive cells 2. TNF-α mRNA | 1. P < 0.05 2. P < 0.05 |
| Zou et al., 2017 | SD rats(male; 15/15) | 250–300 g | BCCAO (ischemia; 20 min; reperfusion; 3 h) | Chloral hydrate (350 mg/kg; i.p.) | NGR1 (100 mg/kg; i.g.) after ischemia | Intragastric administrationof 0.5 ml saline | 1. Cerebral infarction size 2. Relative expression of BDNF mRNA 3. Relative expression of Bcl-2 to β-actin 4. Relative expression of Bax to β-actin | 1. P < 0.01 2. P < 0.01 3. P < 0.01 4. P < 0.01 |
| Tu et al., 2018 | 7-day-old SD rats (male; 9/9) | – | CCL | Isoflurane (2.5%) | NGR1 (15 mg/kg; i.p.; q12 h) for 2 days after ischemia | Not mentioned | 1. The water content of brain tissue 2. Volume of brain infarction 3. TUNEL positive nuclei 4. Brain weight ratio 5. The score of balance beam 6. Percent in the target quadrant 7. PI3K/β-actin 8. P-Akt/T-Akt 9. P-mTOR/T-mTOR 10. P-P70S6K/P70S6K 11. P-4EBP-1/4EBP-1 12. P-JNK/T-JNK 13. P-c-JUN/c-JUN | 1. P < 0.05 2. P < 0.01 3. P < 0.01 4. P < 0.01 5. P < 0.05 6. P < 0.01 7. P < 0.01 8. P < 0.05 9. P < 0.05 10. P < 0.05 11. P < 0.05 12. P < 0.01 13. P < 0.05 |
| Liu et al., 2010 | SD rats (male; 6/6) | 230–250 g | Clamping left renal arteryand vein (ischemia; 45 min; reperfusion; 72 h) | Pentobarbital sodium (50 mg/kg) | NGR1 (40 mg/kg; i.p.) before ischemia and for 3 days after reperfusion | Receiving the same amount of saline | 1. Serum levels of creatinine 2. MPO 3. Relative TNF-α band intensity 4. TUNEL-positive cells 5. Relative p38MAPK band intensity 6. NF-κB band intensity | 1. P < 0.05 2. P <0.05 3. P < 0.05 4. P < 0.05 5. P < 0.05 6. P < 0.05 |
| Li et al., 2014 | SD rats (male; 6/6) | 200–220 g | Clamping superior mesenteric artery (90 min/1 or 72 h) | Pentobarbital sodium (50 mg/kg) | NGR1 (10 mg/kg/h; IVgtt) for 170 min after reperfusion | Receiving the same amount of saline | 1. IκB-α change (%) 2. NF-κB change (%) 3. ATP5D change (%) 4. Zonulaoccludens -1 change (%) 5. Occludin change (%) 6. Claudin-5 change (%) | 1. P < 0.05 2. P < 0.05 3. P < 0.05 4. P < 0.05 5. P < 0.05 6. P < 0.05 |
SD rats, Sprague-Dawley rats; LAD, the left anterior descending coronary artery; SOD, superoxide dismutase; MDA, malondialdehyde; CK, creatine kinase; LDH, lactate dehydrogenase; CK-MB, creatine kinase-MB; TNF-α, tumor necrosis factor-α; GSH-Px, glutathione peroxidase; CAT, catalase; AST, aspartate aminotransferase; AAR/LV, area at risk/left ventricle;+dp/dtmax, maximum ascending rate of left ventricular pressure; −dP/dtmax, maximum descending rate of left ventricular pressure; LVSP, left ventricular systolic pressure; LVDP, left ventricular diastolic pressure; MVC, miniature blood vessel; MVD, microvascular density; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; ATP, adenosine triphosphate; AMP, adenosine monophosphate; IL-1, interleukin-1; IL-8, interleukin-8; NF-κBp65, nuclear factor-kappa Bp65; AMPK, AMP-activated protein kinase; ROCK, Rho-associated coil kinase; MYPT1, myosin phosphatase target subunit-1; NF-κBP65, nuclear factor-κBp65; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor; alpha; VDUP1, vitamin D3 upregulated protein 1; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; c-JNK, c-Jun N-terminal kinase; Bcl-2, B-cell lymphoma-2; MCAO; middle cerebral artery occlusion; BCCAO, bilateral common carotid artery occlusion; BDNF, brain-derived neurotrophic factor; NGR1, notoginsenoside R1; AMI, acute myocardial ischemia; bax, Bcl-2-associated X protein; RBC, red blood cell; MPO, myeloperoxidase; ICAM-1, intercellular cell adhesion molecule-1; TUNEL, TdT-mediated dUTP nick-end labeling; ADP, adenosine diphosphate; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ZO-1, Zonula occludens-1; JAM-1, recombinant junctional adhesion molecule 1; Cav-1, caveolin 1; Cav-3, caveolin 3; AAR, area at risk; T-SOD, total superoxide dismutase; IL-1β, interleukin 1 beta; CHOP, C/EBP homologous protein; GRP78, glucose regulated protein 78; PERK, protein kinase R-like ER kinase; p-PERK, phospho-protein kinase R-like ER kinase; eIf2α, eukaryotic initiation factor 2α; IRE1, inositol-requiring enzyme-1α; ATF6, activating transcription factor 6; 8-OHdG, 8-hydroxydeoxyguanosine; HO-1, heme oxygenase-1; PI3K, p-mTOR, phospho-mammalian target of rapamycin; T-mTOR, P70S6K, protein S6 kinase; P-P70S6K, phospho-protein S6 kinase; P-4EBP-1, phospho-4EBP1.