Effect Of Tanshinone â…¡A On Expression Of Caspase-3, Drp-1and Apoptosis In Rats With Focal Cerebral Ischemia And Reperfusion

BackgroundAcute ischemic cerebrovascular disease is one of the most common clinical disease with high morbidity, high mortality, high disabilities. Ultra‐early thrombolytic therapy in cerebral infarction is the best solution to restore the ischemic brain tissue blood flow. But ischemia‐reperfusion can cause serious delayed neuronal damage, which is called cerebral ischemia and reperfusion injury. In recent years, cerebral ischemia and reperfusion injury has been extensive and in‐depth were studied, and found that neuronal apoptosis after reperfusion was regulated through multi‐link. In the current study, the change of gene expression, the release of excitatory amino acid, calcium overload, the inhibition of protein synthesis, Heat shock protein expression blocked, formation of free radicals, protease activation processes are involved in neuronal apoptosis after cerebral ischemia and reperfusion, but the detailed mechanism is still not entirely clear. Chinese Herbs are the characteristics of China. Salvia is one of the most commonly used traditional Chinese medicine in promoting blood circulation by removing blood stasis. It result in ischemia and reperfusion injury on the brain and other organs and tissues through scavenging oxygen free radicals, protect mitochondria, reduce the calcium overload and has significantly improved on neuronal apoptosis. Drp‐1is the major role of mitochondrial fission. Many studies found that the expression of Drp‐1in nerve cells was increased, subsequent translocation to the mitochondria and activate Caspase system. Ultimately lead to mitochondrial fragmentation and cell apoptosis. Caspase3is considered the most critical caspase in apoptosis, which plays a pivotal role in the apoptotic program initiated by a variety of factors. This experiment trying to study the influence of Tanshinone ⅡA on the expression of Drp‐1and caspase3after cerebral ischemia reperfusion to speculate the possible mechanism of action of pharmacological effects of tanshinone ⅡA. So as to provide a theoretical basis for clinical level study and have a better benefit of ischemic cerebrovascular patients.Objective To study the effect of Tanshinone ⅡA on apoptosis and expression of Caspase‐3and Drp‐1in rats suffered focal cerebral ischemia and reperfusion, and explore the possible mechanism of Tanshinone ⅡA protect on cerebral ischemia‐reperfusion injury.Methods76male SD rats were randomly divided into four groups: sham operation group (S group), ischemia/reperfusion group (I/R group), low dose of Tanshinone (10mg/kg, I/R+Tan1group) and high dose of Tanshinone (30mg/kg, I/R+Tan2group). Each group has19rats. Preparation for focal cerebral ischemia model with Middle cerebral artery suture method after administration by stomach tube for1week.In middle cerebral artery occlusion2h reperfusion for24h, postoperative24h monitoring middle cerebral artery cerebral blood flow.2,3,5‐triphenyhetrazolium chloride was used to detect infarct volume. TUNEL was used to measure apoptosis. Immunohistochemistry and Western blot were used to evaluate the protein expression of Caspase‐3and Drp‐1。Results Compared with I/R group, Tanshinone ⅡA high and low dose group can significantly reduce the number of apoptotic and cerebral infarction, markedly decrease the expression of Caspase‐3and Drp‐1induced in cerebral ischemia/reperfusion24h after MCAO (P <0.05)。But no significantly difference was shown between the infarct volume and TUNEL positive cells (P>0.05). The right middle cerebral artery blood flow of the ischemic area in ischemia‐reperfusion group decreased to31.80%±2.49%after occlusion for2h. Blood flow in Tanshinone ⅡA low dose group and high‐dose group was54.8%±3.27%,58.8%±3.03%, respectively. Conclusion Tanshinone ⅡA can inhibit neuronal apoptosis and mitochondrial lysis in rats following focal cerebral ischemia and reperfusion, the mechanism may be related to improve ischemia district cerebral blood flow,decrease expression of Caspase‐3and Drp‐1.