Tongmai Refreshing Diwan Of Anti-cerebral Ischemic Efficacy And Mechanism Study

Objective: Tongmai Xingnao Dripping Pill is a compound preparation of TCM used to treat ischemia cerebral vascular disease (ICVD). It has efficacies of promoting blood circulation to dissipate blood stasis, restoring consciousness and inducing resuscitation. By researching the effects and the mechanisms of the drug, the test is meant to offer pharmacological evidences to the drug for its clinical use.Methods: We chose the model of middle cerebral artery occlusion(MCAO) by suture embolism in rats, the model of 2-Vasa-occlusion plus hypotension in rats, the model of double CCA and vagus nerve ligated in mice and the model of decollation in mice in order to observe the effects of the drug in opposing ischemia and hypoxia in brain. We determined the clotting time (CT) and observed the internal thrombosis and the microcirculation of piamater to verify the effects of anti-thrombus and microcirculation amelioration of the drug. We chose the two models of hypoxia under ordinary pressure or caused by Sodium Nitrite intoxication to verify the effect of anti-hypoxia of the drug. Through the mensuration of SOD, MDA, GSH-Px and NO in rats' brain we researched the effect of resisting the damages caused by free-radical-peroxidation of the drug. At last, We mensurated the expressions of PI3K, Akt and PTEN in brain by RT-PCR and the expressions of HIF-1αand VEGF in brain by immunohistochemistry to testify if the tested drug can activate the pathway of PI3K/Akt while mensurating the expressions of bcl-2, Bax, CytC and Caspase-3 in brain by immunohistochemistry to testify if the tested drug can activate the pathway of Caspase-3.Results: Tongmai Xingnao Dripping Pill has obvious effects in preventing and curing ICVD. It can decrease the ratio of cerebral infarction and cerebral edema, meliorate pathologic status, polish up symptoms of nervous system. It can prolong the survival time after ischemia and hypoxia damages. It can also prolong the CT, decrease internal thrombosis and meliorate the microcirculation of piamater in mice. It can enhance the activities of SOD and GSH-Px and decrease the content of MDA and NO in rats. It can up-regulate the expressions of PI3K, Akt, HIF-1αand VEGF and down-regulate the expression of PTEN to activate the pathway of PI3K/Akt while down-regulating the expressions of apoptosis encouraging genes such as Bax, CytC and Caspase-3 in order to lighten the damages of ischemia and hypoxia.Conclusion: All the results showed above can elementarily attest to that Tongmai Xingnao Dripping Pill can lighten the damages of ICVD and it is probably related to the up-regulation of PI3K/Akt pathway and the down-regulation of Caspase-3 pathway.