Effects Of Thrombolytic Therapy With Broadened Therapeutic Window On The Free Radical Activity And The Expression Of Caspase-3 In A Rat Model Of Acute Cerebral Infarction

BackgroudAcute ischemic stroke is the main reason of morbidity and mortality, accounting for about 80% of the stroke. Recombinant tissue-type plasminogen activator (r-tPA) for the first time in 1995 was proved to be effective in patients with acute cerebral infarction. Studies have shown that, r-tPA in patients with acute cerebral infarction is still fundamental recanalization therapy, but due to limitations of thrombolytic time window 3 h, the vast majority of patients still lost the chance of treatment. In recent years, EPITHET and DEFUSE studies suggest that thrombolytic therapy in patients with acute cerebral infarction can be extended to 6h, but there is no clear conclusion about the effects of thrombolytic therapy with broadened therapeutic window on the free radical activity and the expression of Caspase-3 in acute cerebral infarction.Objective To explore the effects of thrombolytic therapy with broadened therapeutic window on the nitric oxide (NO), nitric-oxide synthase (NOS), malondialdehude (MDA), superoxide dismutase (SOD) and Caspase-3 in rats with acute cerebral infarction.Methods1. Animal models:Rat models of middle cerebral artery occlusion (MCAO) were established with autologous thrombus. A total of 144 SD rats were randomly divided into control group, stroke group, and 6 h thrombolytic group (n=48 in each group).6 h thrombolytic group was given r-tPA; Control group and stroke group were injected saline.2. Activity of free radicals:The contents of NO, NOS, MDA and SOD of cerebral tissue were assayed by Colorimetric and hydroxylamine method.3. HE staining:The rats after MCAO were sacrificed after 24 h, changes of neurons were observed by HE.4. Immunohistochemistry:Expressions of neuronal NOS (nNOS) and Caspase-3 were determined by immunohistochemical techniques.Results1. Compared with stroke group, the contents of NO, inducible NOS (iNOS), MDA of 6 h thrombolytic group obviously decreased at the same time point (P<0.05).2. Compared with stroke group, the activity of SOD obviously increased of 6 h thrombolytic group obviously increased at the same time point (P<0.05).3. Compared with stroke group, the expression of nNOS obviously decreased (P<0.05).4. Compared with stroke group, the expression of Caspase-3 obviously decreased (P<0.05).ConclusionThrombolytic therapy with broadened therapeutic window can decrease the reaction of oxidative stress and the expression of the apoptosis.