Rosuvastatin preconditioning provides neuroprotection against spinal cord ischemia in rats through modulating nitric oxide synthase expressions.
The study was aimed to investigate the protective effects of rosuvastatin on spinal cord ischemia in rats and to determine the effects of this agent on the expressions of nitric oxide synthase (NOS). Spinal cord ischemia was induced in male Sprague-Dawley rats by occluding the descending thoracic aorta. Experimental groups (n=30 per group) were as follows: sham operation, control (receiving only normal saline), rosuvastatin (5 mg/kg/day for 10 days before occlusion), and rosuvastatin-mevalonate (5 mg/kg/day rosuvastatin and 5 mg/kg/day mevalonate for 10 days before occlusion). Neurological function was assessed at 6, 12, 24, 48, and 72 h after reperfusion. After 72 h reperfusion, spinal cords were harvested for 2,3,5,-triphenyltetrazolium chloride (TTC) staining, TUNEL staining, and nitric oxide (NO) assay. Immunohistochemistry, reverse transcription polymerase chain reaction and western blot were performed to determine the expressions of inducible, endothelial, and neuronal NOS (iNOS, eNOS, and nNOS) in rats with spinal cord ischemia. Spinal cord ischemia thus induced was marked by neurological dysfunction, spinal infarction, and neural cell apoptosis in animals. The results show that rosuvastatin significantly reduced the motor disturbance and the volume of infarctions and attenuated apoptotic neural cells death in the treated rats. Treatment with rosuvastatin remarkably decreased the NO level in spinal cord tissue. In addition, rosuvastatin inhibited iNOS mRNA and protein expression and increased eNOS mRNA and protein expression. However, rosuvastatin had no influence on nNOS mRNA and protein expression. Administrations of mevalonate completely reversed the changes caused by rosuvastatin. These results indicate that rosuvastatin can protect rat spinal cord against ischemia injury by modulation of NOS expressions.
Die
Jun
J
Department of Orthopaedics, The second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
Wang
Kunzheng
K
Fan
Lihong
L
Jiang
Yong
Y
Shi
Zhibing
Z
D000818:Animals; D015415:Biomarkers; D015153:Blotting, Western; D005464:Fluorobenzenes / Q000494:pharmacology*; D006614:Hindlimb / Q000502:physiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007238:Infarction / Q000473:pathology / Q000517:prevention & control; D019194:Ischemic Preconditioning; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D018696:Neuroprotective Agents; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068718:Rosuvastatin Calcium; D020760:Spinal Cord Ischemia / Q000517:prevention & control*; D013449:Sulfonamides / Q000494:pharmacology*; D016896:Treatment Outcome
D015415:Biomarkers; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D011743:Pyrimidines; D012333:RNA, Messenger; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D019001:Nitric Oxide Synthase; D008798:Mevalonic Acid