| Background and Objective: Ischemic cerebrovascular disease is a serious neurological disease, which is very common in middle and eld-aged people. It can lead to disturbance of consciousness and to death and physical disability in severe cases.And it is one of the leading causes of human death and disability.It has been a focus of neurological subjects to find effective treatment to promote functional recovery of the central nervous system. Research data showed that the density of CB1 receptor increased in the rat brain of focal cerebral ischemia and reperfusion, and CB1 receptor agonists not only failed to protect the role, but will accelerate the apoptosis of brain cells. CB2 receptors play an important role in immune cells and regulating the inflammatory responses.In the present research, by simulating the rat focal cerebral ischemia reperfusion injury modelwe, aimed to discuss the effect and mechanism of combination with the CB1 receptor antagonist rimonabant and the CB2 receptor agonist JWH-015, providing a new direction to the drug treatment of cerebral ischemia. Through animal experiments, we explored the protecting effect and possible mechanism of cannabis material on focal cerebral ischemia / reperfusion injury from the aspects of nerve behavior, neuropathology and neurological biochemistry respectively.Methods: The CIR model was built through thread block.120 male rats were randomly divided into sham operation group, operation group ,nimodipine group, low dose rimonabant group, middle dose group and high dose group,low dose JWH-015 group, middle dose group and high dose group,combination group.24 hours later, the neurologic deficit score and infarction area were measured.Then pathological change in injury brain tissue was detected by HE stain.The Caspase-3 and P-erk protein expression were detected by immunohistochemistry.The expressions of Caspase-3 and BDNF mRNA were detected by RT-PCR.At the same time,the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in brain tissue were observed.Results and Conclution:(1)Rimonabant and JWH-015 can relief of neurological behavior disorders after focal cerebral ischemia / reperfusion injury in rats, reduction of neurological behavioral score , reduction of infarct size, reduction of the pathological damage brain tissue . It is suggested that rimonabant and JWH-015 has a protective effect on focal cerebral ischemia / reperfusion injury in rat brain respectively. (2)Rimonabant combination with JWH-015 significantly increased the SOD activity in rat brain tissue after focal cerebral ischemia / reperfusion , decreased the content of MDA , decreased Caspase-3 protein and mRNA expression, increased P-erk protein Expression, increased BDNF protein and mRNA expression.In summary, rimonabant combination with JWH-015 have a significantly protective effect on rats after focal cerebral ischemia / reperfusion injury, which may be related to antagonizing cannabinoid receptor CB1, exciting cannabinoid receptor CB2, inhibiting cell apoptosis, and activation of MAPK pathway.
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