| Dipfluzine(Dip), a novel calcium antagonist of diphenylpiperazines with similar structure to flunarizine, was synthesized by Hebei Medical University. Our previous studies showed that Dip had protective effect against cerebral ischemia, markedly lowered the elevation in concentrations of excited amino acids induced by cerebral ischemia, reduced the area of cerebral infarction and improved the brain edema in rats. Moreover, Dip could decrease the incidence of convulsion and death, improve the cerebral blood flow(CBF) in ischemia rat, ameliorate the amnesia of mouse, inhibit the platelet aggregate significantly, and antagonize the formation of thrombosis in vivo and vitro. It was concluded that Dip possessed the effect of dilation of cerebral blood vessels, increased the cerebral blood flow(CBF) and improved the energy of metabolism of cerebral ischemia, depressed both voltage-dependent calcium channels (VDC) and receptor-operated calcium channels (ROC). But, it had not been studied whether Dip had the protective effect against stroke. In this experiment,the stroke-prone spontaneously hypertensive rat (SHRsp) were used, to observe the therapeutical effect of Dip on stroke.Aim: To observe the therapeutical effect of Dip on stroke in SHRsp.Methods: SHRsp was kept on 5%NaCl food from 8 weeks of age. Blood pressure, heart rate and body weight were measured weekly. The ststolic pressure of the SHRsp was measured with the method of tail-cuff. After onset of stroke, the rats were weighed and divided into five groups:(1) Dip: 80 mg/kg；(2) Dip: 40 mg/kg; (3) Dip: 20 mg/kg; (4) Flu: 40mg/kg; (5) solvent control group. The neurological deficits were evaluated by specially designed scoring system. The symptoms were divided into five degrees. Grade 0 Normal . Grade 1 Stress (mild). Grade 2 Forelimb or head twitch or with stress (severe). Grade 3 Hemiparalysis, body inclined or disabled. Grade 4 Paralysis tremor or convulsion. After the onset of stroke, normal food was given instead of 5%NaCl food.During the experiment, the rats were removed which were died earlier, recorded life span after onset of stroke and bleeded from medial canthus and determined the platelet adhesiveness rate after ten days treatment. After 21 days treatment, rats were killed. Brains and the bodies were weighted and brain coefficient were counted. The brains were put into the 20% formaldehyde solution to immobilization. After desiccation, the brains were embed into the paraffin and stained by HE. The pathomorphology changes were following determinated.(1) The degree of the cerebral hemorrhage .(2) The degree of the edema around hemorrhage .(3) The degree of the degenerate changes of neurons around hemorrhage . (4) The degree of the vasodilatation changes in cerebral cortex. (5) The degree of the vasodilatation changes in the choroids plexus of cerebral ventricle.(6) The number of neurons (neuronal density, ND) in a 1mm linear length of hippoxampus CA1 region was determinted . Result:1.The life span in Dip 80 mg/kg(18.8±2.3 d, P<0.05) and 40 mg/kg(19.8±1.9d, P<0.05) longer than that in solvent control group after the onset of stroke. Flu 40 mg/kg also could prolong the life span after the stroke, 19.6 ±7.0 (d) (P<0.05). 2. The score of neurological deficit decreased significantly compared with solvent control group after treatment with Dip 80 mg/kg 2.1±0.2 (P<0.05) ,40 mg/kg 1.8±0.5 (P<0.01). Flu 40 mg/kg1.9±0.3 (P<0.01). 3. High blood pressure can not be decreased by Dip treatment, the protective effect against stroke can not be explained by decrease the blood pressure. No change was found in HR. 4. Body weight of rats in vehicle group decreased obviously after stroke, however, in Dip80 mg/kg group and 40 mg/kg group the rats, the body weight after stroke 40 mg/kgwas not different from that onset of stroke. 5. Dip and Flu couldreduce the platelet adhesiveness rate markedly, Dip 80 mg/kg platelet adhesiveness rate was 33±6 % (P<0.01), 40 mg/kg was 33±7% (P<0.
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