| Dipfluzine(Dip), a new compound of diphenylpiperazines, was first developed by Hebei Medical University, China. Our previous studies showed that Dip was a more selective and more potent vasodilator on cerebral vessels than cinnarizine in vitro and in vivo. It had therapeutic effect on ischemic brain edema and attenuated platelet aggregation and thrombus formation. From above results, we can guess that Dip maybe produce cerebral protective effect. In this paper, the protective effect of Dip on cerebral ischemia was evaluated with two models: one is permanent focal cerebral ischemia model and the other is focal cerebral ischemia-reperfusion model in rats.Part one Protective effects of Dip against permanent focal cerebral ischemia injury in rats.Aim:1. To establish and evaluate focal cerebral ischemia model and to observe the effects of surgery on the heart rate(HR) and mean arterial blood pressure (MABP) of rats .2. To investigate the protective effect of Dip against permanent focal cerebral ischemia injury in rats.Methods: 1. Sprague-Dawley(SD) rats, female, weighting 250 to 300g, were randomly devided into two groups: ①Sham operation; ②Ischemia. Permanent focal cerebral ischemia model was established and the HR and MABP of rats were recorded. Sham operation was performed without inserting nylon suture into the external carotid artery(ECA) lumen. At 6h after sugery, the neurologic score of each rat was evaluated with blind method, then rats were decapitated and the volume ofinfarct cerebral/volume of whole brain(IV%) was calculated with staining of 2,3,5-triphenyltetra-zolium chloride(TTC). 2. SD rats, female, weighting 250 to 300g, were randomly devided into six groups: ①Sham operation; ②Solvent; ③Flunarizine(Flu) 40mg/kg ; ④Dip 80mg/kg ; ⑤ Dip 40mg/kg ; ⑥Dip 20mg/kg . Drugs were given by gastlic intubation (0.8ml/100g weight). At 6h after surgery, rats of each group were randomly devided into two groups(A and B). Rats of group A were used to evaluate IV% by TTC stain; rats of group B were used to evaluate histopathology changes by HE stain.Results: 1. The surgery had no effects on the HR and MABP of rats. Ischemia group had marked neurologic deficits. Neurologic score was 7.8±0.4 and the IV%(12.2±0.5) was stable(coefficient of variation is 4%). No neurologic deficits and ischemia area were found in the sham operation group . 2. The neurologic score was decreased to 5.5±0.8 and 6.0±0.6 in the group of Dip 80mg/kg and 40mg/kg, which was lower(P<0.01) than that of solvent group(7.7±0.8). Dip 80mg/kg and Dip 40mg/kg also decreased the IV% from 12.0±0.7%(solvent) to 4.6±1.5% and 7.3±1.7%, respectively(P<0.01). This kind of protective effect is dose dependent. Under a light microscope, degenerative changes and necrosis(manifested as red neurons, vacuolation, et al.) were seen in the third cortex of brain slice in solvent group. Dip80mg/kg and 40mg/kg and Flu 40mg/kg reduced the brain damage according to the results of obtaining from light microscope observation. Dip 20mg/kg didn't reduce neurologic score and IV% and didn't ameliorate brain damage.Conclusion: 1. This model is stable. It can be used for evaluating pharmacodynamics of new drugs. 2. Dip has protective effects against permanent focal cerebral ischemia injury in rats.Key words: cerebral ischemia, cerebral infarct volume, neurologic score, animal model, rat, dipfluzine, flunarizine.Part two Protective effect of Dip against focal cerebral ischemia-reperfusion injury in rats.Aim: 1. To establish and evaluate focal cerebral ischemia-reperfusion model .2. To investigate the effects of Dip on neurological deficits, cerebral infarct volume, MDA content and SOD activity.Methods: 1. SD rats, female, weighting 230 to 270g, were randomly devided into two groups: ①Sham operation; ②Ischemic 2h and reperfusion 4h(I2R4). Focal cerebral ischemia-reperfusion injury model was established and cerebral blood flow(CBF) was recorded. At 4h after reperfusion, the n...
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