Propofol Ameliorates Hyperglycemia-Induced Cardiac Hypertrophy and Dysfunction via Heme Oxygenase-1/Signal Transducer and Activator of Transcription 3 Signaling Pathway in Rats*
Bibliographic record
Abstract
OBJECTIVES: Heme oxygenase-1 is inducible in cardiomyocytes in response to stimuli such as oxidative stress and plays critical roles in combating cardiac hypertrophy and injury. Signal transducer and activator of transcription 3 plays a pivotal role in heme oxygenase-1-mediated protection against liver and lung injuries under oxidative stress. We hypothesized that propofol, an anesthetic with antioxidant capacity, may attenuate hyperglycemia-induced oxidative stress in cardiomyocytes via enhancing heme oxygenase-1 activation and ameliorate hyperglycemia-induced cardiac hypertrophy and apoptosis via heme oxygenase-1/signal transducer and activator of transcription 3 signaling and improve cardiac function in diabetes. DESIGN: Treatment study. SETTING: Research laboratory. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: In vivo and in vitro treatments. MEASUREMENTS AND MAIN RESULTS: At 8 weeks of streptozotocin-induced type 1 diabetes in rats, myocardial 15-F2t-isoprostane was significantly increased, accompanied by cardiomyocyte hypertrophy and apoptosis and impaired left ventricular function that was coincident with reduced heme oxygenase-1 activity and signal transducer and activator of transcription 3 activation despite an increase in heme oxygenase-1 protein expression as compared to control. Propofol infusion (900 μg/kg/min) for 45 minutes significantly improved cardiac function with concomitantly enhanced heme oxygenase-1 activity and signal transducer and activator of transcription activation. Similar to the changes seen in diabetic rat hearts, high glucose (25 mmol/L) exposure for 48 hours led to cardiomyocyte hypertrophy and apoptosis, both in primary cultured neonatal rat cardiomyocytes and in H9c2 cells compared to normal glucose (5.5 mmol/L). Hypertrophy was accompanied by increased reactive oxygen species and malondialdehyde production and caspase-3 activity. Propofol, similar to the heme oxygenase-1 inducer cobalt protoporphyrin, significantly increased cardiomyocyte heme oxygenase-1 and p-signal transducer and activator of transcription protein expression and heme oxygenase-1 activity and attenuated high-glucose-mediated cardiomyocyte hypertrophy and apoptosis and reduced reactive oxygen species and malondialdehyde production (p < 0.05). These protective effects of propofol were abolished by heme oxygenase-1 inhibition with zinc protoporphyrin and by heme oxygenase-1 or signal transducer and activator of transcription 3 gene knockdown. CONCLUSIONS: Heme oxygenase-1/signal transducer and activator of transcription 3 signaling plays a critical role in propofol-mediated amelioration of hyperglycemia-induced cardiomyocyte hypertrophy and apoptosis, whereby propofol improves cardiac function in diabetic rats.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".