title: [Role of nitric oxide in pathogenesis of cold nerve injury].
abstract: OBJECTIVE
  To study the role of nitric oxide (NO) in the pathogenesis of cold nerve injury and to explore its mechanism.
  
  
  METHODS
  Cold nerve injury model was established in rat's sciatic nerve. Consistent and intermittent cooling of 4 degrees C for 2 hours were respectively applied to the sciatic nerves. Nerve samples were taken at different time points: immediately post-cooling and 4 h, 1 d & 3 d post-cooling. The group of aminoguanidine (AG) intervention was also established. Then NO levels in the nerves and blood serum were detected. Induced nitric oxide synthase (iNOS) in ganglion was determined by immunohistochemistry. Morphology of cooled sciatic nerves in the AG groups (consistent & intermittent cooling AG groups) and control groups (1 d time point of consistent & intermittent cooling groups) was observed by light microscope and electron microscope.
  
  
  RESULTS
  At the time points of immediacy, 4 h, 3 d in the consistent cooling groups and the time points of immediacy, 4 h, 1 d in the intermittent cooling groups, different incremental degrees of NO levels in the cooled nerves (0.146 +/- 0.047), (0.216 +/- 0.048), (0.137 +/- 0.035), (0.154 +/- 0.027), (0.260 +/- 0.027), (0.218 +/- 0.042) micromol/g as compared with those of controls (0.098 +/- 0.022), (0.158 +/- 0.030), (0.085 +/- 0.020), (0.127 +/- 0.016), (0.72 +/- 0.027), (0.174 +/- 0.026) micromol/g, P < 0.01, P < 0.05). And NO levels in the cooled nerves at the time points of 4 h, 1 d, 3 d in the intermittent cooling groups were higher than those in the consistent cooling groups (P < 0.01, P < 0.05). NO levels in blood serum at the time points of immediacy and 1 d in the intermittent cooling groups (4.98 +/- 1.33) micromol/L, (4.02 +/- 0.68) micromol/L were higher than those in the consistent cooling groups (2.47 +/- 0.36) micromol/L, (3.00 +/- 0.67) micromol/L, P < 0.01). Both in consistent cooling and intermittent cooling groups, different incremental degrees of areas and integrated optical density (IOD) of iNOS positive staining in ganglions were found in cooled side as compared with the control side at different time points (P < 0.01, P < 0.05, P > 0.05), while those at the time point of immediacy in the intermittent cooling groups (131 686 +/- 24 549) , (4.1 +/- 0.13) x 10(9) were higher than those in the consistent cooling groups (78 558 +/- 34 849), (2.1 +/- 0.93) x 10(9), P < 0.05. NO level of cooled nerves in the intermittent cooling AG group (0.178 +/- 0.030) micromol/g was lower than those at the time point of 1 d in intermittent cooling groups (0.218 +/- 0.042) micromol/g, P < 0.05). Also a reduction of NO levels of blood serum, areas and IOD of iNOS positive staining was found in the AG groups as compared with the control groups (P < 0.05) while the reduction was more significantly found in the intermittent cooling AG group (P < 0.01, P < 0.05). Through light microscope and electron microscope, more severe pathological injury of cooled nerve was seen in the intermittent cooling group as compared with 1d time point of the consistent cooling groups, and a marked reduction of pathological injury was found when AG was administered. It was also more significant in the intermittent cooling AG group.
  
  
  CONCLUSIONS
  NO plays a causative role in the pathogenesis of cold nerve injury, especially in intermittent cold nerve injury. The expression of iNOS is the main source of NO. Production of free radicals and the resulting toxic injury may be its main mechanism.
authors.affiliation: Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: You
authors.initials: Y
authors.lastname: Wu
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Jia
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Geng
authors.forename: Fang-Yan
authors.initials: FY
authors.lastname: Liu
authors.forename: Jue-Xian
authors.initials: JX
authors.lastname: Song
authors.forename: Hao
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D003080:Cold Temperature; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000473:pathology*
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase