| Dipfluzine(Dip), a novel calcium antagonist of diphenylpiperazines with similar structure to flunarizine, was synthesized by Hebei medical university. It had been tested that Dip could dilate various blood vessels. It had selective vasodilatory effect on noradrenaline(NA) and high potassium evoked contraction in pig basilar artery. It could selectively reduce the vertebral artery resistance in anesthesia dogs and antagonize brain edema in rats by increasing the blood flow of ischemia regions; Moreover, Dip could improve amnesia and protect mice against the acute cerebral hypoxia. Our present study is to make model of the whole cerebral ischemia reperfusion by using the four vessel occlusion(4-VO) method of Pulsinelli, to measure the content of H2O in brain tissue, and to observe the amnesia, the electroencephalogram(EEG) and pathologic changes after brain injury. Thus, we can study the protective effect of Dip on brain edema and ischemia injury. Moreover, by measuring the activity of SOD, MDA and LDH we could further study the antagonism effect of Dip on lipid peroxidation. The concrete experiments are as follows: 1．Effects of Dip on the content of H2O in brain tissueand some biochemistry indexes in the forepart of cerebral ischemia reperfusion period.Aim: To study the protective effect of Dip on the forepart of ischemia reperfusion injury by measuring the content of H2O and some biochemistry indexes in brain tissue.Method: To make the rat model of reperfusion 1 hour after 30 min of the whole cerebral ischemia by using Pusinellis 4-VO method. SD rats (weighing 250-300g, female, healthy) were randomly divided into 6 groups: ①Sham operation control group; ②Solvent control group(solvent, ig); ③Flunarizine group(40mg/kg, ig); ④High dose Dip group(80mg/kg, ig); ⑤Middle dose Dip group(40mg/kg, ig); ⑥Low dose Dip group(20mg/kg, ig). Rats in sham operation control group were only treated by operating process, the common carotid arteries and vertebral arteries were not occluded. Rats in other groups were treated by operation to make model. Drugs were given by 0.8ml/100g. Thirty minutes before ischemia and after reperfusion drugs were given respectively. Rats in sham operation control group were killed 24h after surgery. Rats in other groups were killed after reperfusion. Brains were removed and the left parts were used to measure the content of H2O, the right parts were used to measure the activity or content of SOD, MDA and LDH. The content of protein in the brain tissue were determined by Coomassive technique.Results: The content of H2O in rats of sham operation group was 78.3%. After ischemia and reperfusion, the content of H2O was 80.9% in solvent group, which was different from that of sham operation control group. However, in Dip(80mg/kg, 40mg/kg) groups, the content of H2O was 78.8%, 79.1% respectively. Brain edema was improved obviously. The content of H2O was also decreased by Flu(79.2%). However, there was no significant difference among the Flu and Dip(high and middle doses) groups. Moreover, from the biochemistry indexes we could see that the content of MDA of the brain tissue was increased obviously after ischemia and reperfusion injury, and the activity of SOD and LDH was clearly decreased, which was different from that of sham operation control group. In Flu and Dip(three doses) groups, the content of MDA was decreased in different degrees. Flu and Dip(high and middle dose) could increased the activity of LDH and SOD, but Dip(low dose) had no significant effect on LDH and SOD.Conclusion: Dip had some protective effect on the forepart of the ischemia and reperfusion period, which was possibly due to the antagonism effect on lipid peroxidation.Key Words: Dipfluzine,brain edema,lipid oxidation,SOD,MDA,LDH,the whole cerebral ischemia,reperfusion...
|
PDF Full Text Request