毛冬青总黄酮对小鼠血瘀合并脑缺血耐受模型的影响

Study on intervention action of total flavonoids from Ilex Pubescens Radix on animal models of cerebral ischemic tolerance with blood stasis

采用小鼠连续注射地塞米松复制血瘀模型,并给予相应药物,连续灌服15 d后,阻断双侧颈总动脉血流10 min,恢复灌注5 d后,再次阻断双侧颈总动脉30 min。再灌注24 h,复制小鼠脑缺血耐受模型。取血测全血黏度;断头取脑,一半脑置于10%福尔马林溶液中固定,用于HE染色;另一半脑用生理盐水制备脑匀浆,用于测定脑组织匀浆中ATPase活力、GLU含量、脑匀浆中NOS表达;探讨毛冬青总黄酮对小鼠血瘀合并脑缺血耐受模型的保护作用机制。结果显示,与缺血耐受组(模型组)比较,高剂量毛冬青总黄酮组能够显著降低小鼠血流变高、中、低切值(P<0.01),中、低剂量毛冬青总黄酮组能够显著降低小鼠血流变低切值(P<0.01),明显减轻小鼠血流变中切值(P<0.05),中剂量毛冬青总黄酮组能够明显降低小鼠血流变高切值(P<0.05);高剂量毛冬青总黄酮能够显著升高各ATPase活力(P<0.01),中剂量毛冬青总黄酮能够显著增强Na+-K+-ATPase活力(P<0.01),低剂量毛冬青总黄酮能够明显升高Na+-K+-ATPase活力(P<0.05);高剂量毛冬青总黄酮能够显著降低Glu含量(P<0.01),其他给药剂量能够明显降低Glu含量(P<0.05);高剂量毛冬青总黄酮组可显著降低小鼠脑组织中TNOS,i NOS的水平(P<0.01),中剂量毛冬青总黄酮组可明显降低小鼠脑组织中TNOS,i NOS的水平(P<0.05),低剂量毛冬青总黄酮组可明显降低小鼠脑组织中i NOS的水平(P<0.05);各剂量毛冬青总黄酮均可改善脑组织病理改变。提示毛冬青总黄酮可从降低全血黏度、抑制炎症介质NOS的表达、降低Glu含量、升高ATPase活力、改善缺血脑部组织病理方面保护小鼠血瘀合并脑缺血耐受模型的脑损伤。

The mice models of blood stasis were established by injecting dexamethasone into the intramuscular of side the thigh for successive 15 days, and giving related drugs via an intragastric administration. Firstly, the method of blocking the bilateral common ca- rotid artery （CCA） was used for I0 minutes, and then perfusion restore for 5 days. Secondly, the method of CCA was used for 30 mi- nutes, and then reperfusion for 24 hours. The whole blood viscosity and plasma viscosity, the activity of NOS and ATPase and the level of NOS, and the content of Glu in the ischemic brain were measured. The morphological changes of brain tissue were observed by eosin （HE） staining technique. The results showed that compared with IPC model group the large doses of the flavonoids could reduce the viscosity of whole blood significantly （P 〈 O. O1 ）. The small and medium doses of flavonoids could reduce the whole blood viscosity low-shear obviously （P 〈 0. O1 ）. The medium doses of flavonoids could reduce the midst-shear obviously （ P 〈 0.05 ）. The large and medium dose of flavonoids could significantly improve the ATP activity （P 〈 0. 01 ）. The medium dose of flavonoids could improve the Na＋ -K ＋ -ATPase activity significantly （ P 〈 0. 01 ）. The small dose of flavonoids could improve the Na ＋ -K ＋ -ATPase activity obviously （ P 〈 0. 05 ）. The large doses of flavonoids could reduce the content of gluin the isehemie brain significantly （ P 〈 0. 01 ）. And the others does of flavonoids could reduce the content of gluin the ischemic brain obviously （P 〈 0. 05 ）. The large doses of flavonoids could reduce the activity of TNOS and iNOS significantly （ P 〈0. 01 ）. The medium doses of flavonoids could reduce the activity of TNOS and iNOS obviously （ P 〈 0. 05 ）. The small doses of flavonoids could reduce the activity of iNOS obviously （ P 〈 0. 05 ）. Total flavonoids could obviously or significantly decrease the whole blood viscosity, the activity of NOS and the content of gluin the ischemic brain, in- crease the activity of ATPase significantly or obviously, could significantly relieve the degree of pathological injury of brain tissue of ani- mal models.