中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2004年
5期
333-337
,共5页
梅和珊%苏素文%李军霞%李海芳%王永利
梅和珊%囌素文%李軍霞%李海芳%王永利
매화산%소소문%리군하%리해방%왕영리
钙通道阻滞剂%双苯氟嗪%氟桂利嗪%内皮素-1%脑缺血%自由基类%氢清除法
鈣通道阻滯劑%雙苯氟嗪%氟桂利嗪%內皮素-1%腦缺血%自由基類%氫清除法
개통도조체제%쌍분불진%불계리진%내피소-1%뇌결혈%자유기류%경청제법
calcium channel blockers%dipfluzine%flunarizine%endothelin-1%cerebral ischemia%free radicals%hydrogen clearance technique
目的评价双苯氟嗪(Dip)和氟桂利嗪(Flu)在大鼠局灶性脑缺血再灌注模型中的神经保护作用.方法 将内皮素-1(ET-1)灌注到大脑中动脉附近制备大鼠局灶性脑缺血再灌注模型,并于灌注ET-1后30min和4.5h腹腔注射溶剂、Dip 10,20和40mg·kg-1和Flu 20mg·kg-1,采用氢清除法监测灌注ET-1前后、纹状体血流变化,并对缺血后24h脑梗塞面积、血清中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量的变化进行了测定.结果Dip20和40mg·kg-1于灌注ET-1后70和100min明显改善缺血侧纹状体血流量下降;Flu20mg·kg-1的作用较弱,仅于灌注ET-1后100min明显改善缺血侧纹状体血流量;Dip可以剂量依赖性的降低脑梗塞面积(r=0.9797,P<0.01),同剂量Flu可产生相似的作用;各剂量组Dip和Flu均可增加血清中SOD活性、降低MDA含量.结论Dip和Flu对脑缺血再灌注损伤有明显的保护作用,Dip改善脑血流的作用略强于Flu其保护作用的机制与改善脑血流的搞氧化作用有关.
目的評價雙苯氟嗪(Dip)和氟桂利嗪(Flu)在大鼠跼竈性腦缺血再灌註模型中的神經保護作用.方法 將內皮素-1(ET-1)灌註到大腦中動脈附近製備大鼠跼竈性腦缺血再灌註模型,併于灌註ET-1後30min和4.5h腹腔註射溶劑、Dip 10,20和40mg·kg-1和Flu 20mg·kg-1,採用氫清除法鑑測灌註ET-1前後、紋狀體血流變化,併對缺血後24h腦梗塞麵積、血清中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量的變化進行瞭測定.結果Dip20和40mg·kg-1于灌註ET-1後70和100min明顯改善缺血側紋狀體血流量下降;Flu20mg·kg-1的作用較弱,僅于灌註ET-1後100min明顯改善缺血側紋狀體血流量;Dip可以劑量依賴性的降低腦梗塞麵積(r=0.9797,P<0.01),同劑量Flu可產生相似的作用;各劑量組Dip和Flu均可增加血清中SOD活性、降低MDA含量.結論Dip和Flu對腦缺血再灌註損傷有明顯的保護作用,Dip改善腦血流的作用略彊于Flu其保護作用的機製與改善腦血流的搞氧化作用有關.
목적평개쌍분불진(Dip)화불계리진(Flu)재대서국조성뇌결혈재관주모형중적신경보호작용.방법 장내피소-1(ET-1)관주도대뇌중동맥부근제비대서국조성뇌결혈재관주모형,병우관주ET-1후30min화4.5h복강주사용제、Dip 10,20화40mg·kg-1화Flu 20mg·kg-1,채용경청제법감측관주ET-1전후、문상체혈류변화,병대결혈후24h뇌경새면적、혈청중초양화물기화매(SOD)활성화병이철(MDA)함량적변화진행료측정.결과Dip20화40mg·kg-1우관주ET-1후70화100min명현개선결혈측문상체혈류량하강;Flu20mg·kg-1적작용교약,부우관주ET-1후100min명현개선결혈측문상체혈류량;Dip가이제량의뢰성적강저뇌경새면적(r=0.9797,P<0.01),동제량Flu가산생상사적작용;각제량조Dip화Flu균가증가혈청중SOD활성、강저MDA함량.결론Dip화Flu대뇌결혈재관주손상유명현적보호작용,Dip개선뇌혈류적작용략강우Flu기보호작용적궤제여개선뇌혈류적고양화작용유관.
AIM To compare the protective effects of dipfluzine (Dip) and flunarizine (Flu) on the focal cerebral ischemia-reperfusion injury in rats. METHODSEndothelin-1(ET-1) was perfused to the proximity of the middle cerebral artery (MCA) to induce focal cerebral ischemia-reperfusion model. Solvent, Dip 10, 20 and 40 mg·kg-1 and Flu 20 mg·kg-1 were given ip 30 min and 4.5 h after ET-1 perfusion. The changes in cerebral blood flow (CBF) in striatum before and after ET-1 perfusion were characterized using hydrogen clearance technique. The infarct volume, the activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in serum were measured respectively at 24 h after ET-1 application to evaluate the effects of Dip and Flu. RESULTS Dip 20 and 40 mg·kg-1 significantly alleviated the CBF decrease at 70 and 100 min after ET-1 perfu- sion, but Dip 10 mg·kg-1 did not. Flu 20 mg·kg-1 could enhance CBF only at 100 min, which showed relative weak effect on CBF. A significant reductions in infarct volume were found in Dip-treated groups as well as in Flu-treated group compared with the solvent group, and Dip showed a dose-dependent reduction(r=0.9797, P<0.01). Furthermore, Dip and Flu also raised SOD activity and decreased MDA content in serum. CONCLUSION Dip and Flu showed significant protective effects against cerebral ischemia-reperfusion injury via increasing CBF in ischemic-regions and their antioxidant activity. Dip showed a relatively stronger effect than Flu in improving CBF.