Improved peripheral nerve regeneration in streptozotocin-induced diabetic rats by oral lumbrokinase

Am J Chin Med. 2015;43(2):215-30. doi: 10.1142/S0192415X15500147. Epub 2015 Mar 19.

Abstract

We assessed the therapeutic effects of lumbrokinase, a group of enzymes extracted from the earthworm, on peripheral-nerve regeneration using well-defined sciatic nerve lesion paradigms in diabetic rats induced by the injection of streptozotocin (STZ). We found that lumbrokinase therapy could improve the rats' circulatory blood flow and promote the regeneration of axons in a silicone rubber conduit after nerve transection. Lumbrokinase treatment could also improve the neuromuscular functions with better nerve conductive performances. Immunohistochemical staining showed that lumbrokinase could dramatically promote calcitonin gene-related peptide (CGRP) expression in the lamina I-II regions in the dorsal horn ipsilateral to the injury and cause a marked increase in the number of macrophages recruited within the distal nerve stumps. In addition, the lumbrokinase could stimulate the secretion of interleukin-1 (IL-1), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) in dissected diabetic sciatic nerve segments. In conclusion, the administration of lumbrokinase after nerve repair surgery in diabetic rats was found to have remarkable effects on promoting peripheral nerve regeneration and functional recovery.

Keywords: Earthworm; Lumbrokinase; Peripheral Nerve Regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Circulation / drug effects
  • Calcitonin Gene-Related Peptide / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology*
  • Endopeptidases / administration & dosage*
  • Endopeptidases / isolation & purification
  • Endopeptidases / pharmacology*
  • Interleukin-1 / metabolism
  • Macrophages
  • Male
  • Nerve Growth Factor / metabolism
  • Nerve Regeneration / drug effects*
  • Neural Conduction / drug effects
  • Oligochaeta / enzymology
  • Platelet-Derived Growth Factor / metabolism
  • Rats, Sprague-Dawley
  • Sciatic Nerve / blood supply
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / physiology*
  • Streptozocin
  • Transforming Growth Factor beta / metabolism

Substances

  • Interleukin-1
  • Platelet-Derived Growth Factor
  • Transforming Growth Factor beta
  • Streptozocin
  • Nerve Growth Factor
  • Endopeptidases
  • lumbrokinase
  • Calcitonin Gene-Related Peptide