Triptolide improves systolic function and myocardial energy metabolism of diabetic cardiomyopathy in streptozotocin-induced diabetic rats.

Abstract

BACKGROUND:

Triptolide treatment leads to an improvement in Diabetic Cardiomyopathy (DCM) in streptozotocin-induced diabetic rat model. DCM is characterized by abnormal cardiac energy metabolism. We hypothesized that triptolide ameliorated cardiac metabolic abnormalities in DCM. We proposed (31)P nuclear magnetic resonance ((31)P NMR) spectrometry method for assessing cardiac energy metabolism in vivo and evaluating the effect of triptolide treatment in DCM rats.

METHODS:

Six weeks triptolide treatment was conducted on streptozotocin-induced diabetic rats with dose of 100, 200 or 400 μg/kg/day respectively. Sex- and age-matched non-diabetic rats were used as control group. Cardiac chamber dimension and function were determined with echocardiography. Whole heart preparations were perfused with Krebs-Henseleit buffer and (31)P NMR spectroscopy was performed. Cardiac p38 Mitogen Activating Protein Kinase (MAPK) was measured using real time PCR and western blot analysis.

RESULTS:

In diabetic rats, cardiac mass index was significantly higher, where as cardiac EF was lower than control group. (31)P NMR spectroscopy showed that ATP and pCr concentrations in diabetic groups were also remarkably lower than control group. Compared to non-treated diabetic rats, triptolide-treated diabetic groups showed remarkable lower cardiac mass index and higher EF, ATP, pCr concentrations, and P38 MAPK expressions. Best improvement was seen in group treated with Triptolide with dose 200 μg/kg/day.

CONCLUSIONS:

(31)P NMR spectroscopy enables assessment of cardiac energy metabolism in whole heart preparations. It detects energy metabolic abnormalities in DCM hearts. Triptolide therapy improves cardiac function and increases cardiac energy metabolism at least partly through upregulation of MAPK signaling transduction.

• Authors: Zhongshu Liang, Sunnar Leo, Helin Wen, Mao Ouyang, Weihong Jiang, Kan Yang
• Journal: BMC cardiovascular disorders (BMC Cardiovasc Disord) Vol. 15 Pg. 42 (May 13 2015) ISSN: 1471-2261 [Electronic] England
• PMID: 25967112 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Diterpenes
• Epoxy Compounds
• Phenanthrenes
• triptolide
• Streptozocin
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Diabetes Mellitus, Experimental (physiopathology)
• Diabetic Cardiomyopathies (diagnostic imaging, drug therapy, physiopathology)
• Diterpenes (therapeutic use)
• Energy Metabolism
• Epoxy Compounds (therapeutic use)
• Magnetic Resonance Spectroscopy
• Myocardium (metabolism)
• Phenanthrenes (therapeutic use)
• Rats, Sprague-Dawley
• Streptozocin
• Systole (drug effects)
• Ultrasonography
• p38 Mitogen-Activated Protein Kinases (metabolism)