The Expressions Of ROCKⅡ,NF-kappaB And COX-2 In The Brain Stem Of Migraine Model Rats

BackgroundsMigraine is a kind of paroxysmal neurovascular dysfuntion with character of recurrence of unilateral or bilateral headache. Its pathogenesis has not been clarified, but it is considered that activation of trigeminal vascular system plays an important role in it.Rho kinase is the main effector molecules of Rho protein downstream. Two isoforms of ROCK(ROCK I and ROCK II)have been identified, and Rock II is mainly expressed in central nerve system. Rho / ROCK pathway in the development and maintenance of chronic pain plays an important role. Rho-NF-kB axis participates in many diseases' mechniam such as tumors, high blood pressure-related diseases. Rho kinase inhibitors can inhibit the activation of NF-kBNuclear factor-kappaB (NF-kB) is a prevalent rapid response transcription factor of a cell-mediated intracellular signal transduction, which can regulate gene expression. It is found that NF-kB is highly up-regulated in nucleus trigeminalis caudalis and dura mater where trigeminal nerve distributes in migraine model induced by nitroglycerin. NF-kB plays an important role in the neurogenic inflammation of migraine, which need to be further studied.Cyclooxygenase-2 (COX-2) is an induing-cyclooxygenase, which is also called "inflammation gene". COX-2 is expressed very low in normal physiological status, but rapidly high-expressed after stimulation, which is involved in the inflammation-associated pathophysiological process. COX-2 is the transcriptional material regulated by the NF-kB. COX-2 inhibitor can terminates migraine through inhibiting center sensitization.ObjectivesTo research the effect of ROCK II, nuclear factor-kappaB and COX-2 proteins on occurrence of migraine, we will detect their expression changes in brainstem of migraine model rats during the stages attack and intermission of migraine in experimental migraine model induced by Nitroglycerin.Methods1. Grouping and building model: 18 Sprague-Dawley (SD) rattus were divided into two randomized groups. Model group:according to Tassorelli that NTG was injected subcutaneouly by 10mg(2ml)/mg, 1 time every week for 5 weeks; NS control group: NS was injected subcutaneouly by 10mg/kg, 1 time every week for 5 weeks.2. At 2 hour or the 4^th day after NTG was injected subcutaneously for the 5^th , the brain stem was taken out from the rats and stored in liquid nitrogen.3. The expressions of ROCK II,NF-kappaB and COX-2 protein in the brain stem was investigated by Western-blotting.Results1. In the period of onset, the expression of ROCK II protein, nuclear factor-kappaBp65 protein, COX-2 protein in the brain stem were all upregulated (p<0.05) in the model group compared with the respective control group and its intermission group; there were no statistical difference (p>0.05) between and intermission group and control group2. There is mild negative correlation between ROCK II protein and NF-kBp65 protein in onset group and intermission group (r=-0.0040 , p<0.05), but there is obvious positive correlation b etween NF-kBp65 protein and COX-2 protein in onset group and intermission group(r=0.5098, p<0.05).Conclusions1. ROCK II protein, nuclear factor-kappaB potein, COX-2 protein may be involved in the process of migraine.2. Nuclear factor-kappaB protein may induce COX-2 protein and upregulate it in the occurrence of migraine.