Anti-apoptotic and neuroprotective effects of Tetramethylpyrazine following spinal cord ischemia in rabbits

BMC Neurosci. 2006 Jun 14:7:48. doi: 10.1186/1471-2202-7-48.

Abstract

Background: Tetramethylpyrazine (TMP) is one of the most important active ingredients of a Chinese herb Ligusticum wallichii Franchat, which is widely used in many ischemia disorders treatments. However, the exact mechanism by which TMP protects the spinal cord ischemia/reperfusion (I/R) injury is still unknown. For this purpose, rabbits were randomly divided into sham group, control group and TMP group. After the evaluation of neurologic function, the spinal cords were immediately removed for biochemical and histopathological analysis. Apoptosis was measured quantitatively by the terminal transferase UTP nick end-labeling (TUNEL) method and confirmed by electron microscopic examination, the expression of Bax and Bcl-2 was immunohistochemically evaluated and quantified by Western blot analysis.

Results: Neurologic outcomes in the TMP-group were significantly better than those in the control group (P < 0.05). TMP decreased spinal cord malondialdehyde (MDA) levels and ameliorated the down regulation of spinal cord superoxide dismutase (SOD) activity. TMP significantly reduced the loss of motoneurons and TUNEL-positive rate. Greater Bcl-2 and attenuated Bax expression was found in the TMP treating rabbits.

Conclusion: These findings suggest that TMP has protective effects against spinal cord I/R injury by reducing apoptosis through regulating Bcl-2 and Bax expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Male
  • Malondialdehyde / metabolism
  • Microscopy, Electron, Transmission
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / etiology
  • Nerve Degeneration / prevention & control
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pyrazines / pharmacology*
  • Pyrazines / therapeutic use
  • Rabbits
  • Spinal Cord / blood supply
  • Spinal Cord / drug effects*
  • Spinal Cord / physiopathology
  • Spinal Cord Ischemia / drug therapy*
  • Spinal Cord Ischemia / physiopathology
  • Spinal Cord Ischemia / prevention & control
  • Superoxide Dismutase / drug effects
  • Superoxide Dismutase / metabolism
  • Treatment Outcome
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • bcl-2-Associated X Protein / antagonists & inhibitors
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antioxidants
  • Enzyme Inhibitors
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrazines
  • bcl-2-Associated X Protein
  • Malondialdehyde
  • Superoxide Dismutase
  • tetramethylpyrazine