β-淀粉样蛋白(Aβ32-35)的血管活性及其机制探讨

A study on the mechanism underlying vasoactivity of beta-amyloid protein fragment 32-35

目的 研究Ａβ３２－３５的血管活性机制。方法 建立鼠后爪垫皮肤微血管网模型，将新鲜制备的Ａβ３２－３５（１０μｍｏｌ）溶液、Ａｃｈ（１００μｍｏｌ）、ＳＮＰ（１００μｍｏｌ）、ＢＱ－１２３（１０μｍｏｌ）以及抗氧化剂ＳＯＤ（１００Ｕ／ｍｌ）、Ｃａｔａｌａｓｅ （１００Ｕ／ｍｌ）和ＮＡＣＥ（１００μｍｏｌ）溶液按一定顺序由微型泵驱动灌注微血管网、激光多普勒血流监测仪测量微血管 血液流量的变化。结果 灌注 Ａβ３２－３５引起血管收缩反应（ＶＣ）；灌注Ａｃｈ和 ＳＮＰ引起血管舒张反应（ＶＤ）。先灌 注Ａβ３２－３５，立即或２ｈ后再予Ａｃｈ均造成Ａｃｈ的ＶＤ消失：但立即予ＳＮＰ或２ｈ后再予ＳＮＰ则造成ＳＮＰ的ＶＤ减 弱或不受影响。先灌注ＢＱ－１２３或Ｃａｔａｌａｓｅ或ＮＡＣＥ后予Ａβ－３２－３５；再予Ａｃｈ，则Ａβ３２－３５引起的ＶＣ反应消失；但Ａｃｈ的ＶＤ反应在不同时间点得到部分恢复，ＳＯＤ对Ａβ３２－３５及Ａｃｈ的血管反应无影响。结论 提供活体鼠Ａβ３２－３５收缩外周微血管依据：其机制通过内皮细胞和平滑肌细胞的长短期作用实现，氧自由基和内皮素－１参与Ａβ３２－３５的缩血管作用。

Objective To explore the mechanism underlying vasoactivity of beta-amyloid fragment 32-35. Methods Using rat hind footpad skin microvasculature as a model. Perfusion of freshly prepared soluble beta- amyloid (10μmol). acetvkholine (100μmol),sodium nitroprusside (100μmol). BQ-123 (10μmol) and antioxidant SOD (100U/ml), Catalase (100U/ml) and NACE (100μmol) is maintained by a peristaltic pump .Microvascular blood flow was monitored by Laser Doppler flowmetry. Results Perfusion of Aβ, induced vasoconstriction (VC), perfusion of Ach and SNP resulted in vasodilation (VD). Perfusion of Aβ, followed immediately or 2h later by acetylcholine for 30mm did not cause vasodilation, but by SNP for 15mm resulted in the decreased or unchanged vasodilation. Perfusion of BQ-123 or catalase or NACE, followed by Ach, then by Ach, the result showed that the vasoconstriction response to Aβ failed to produce and vasodilation to Ach was partially restored at different time. SOD had no vascular effect on Aβ and Ach. Conclusions This study provide vasoconstriction response to Aβ in the peripheral microvasculature of rats in vivo, which contribute to short-term and long-term function of endothe- lial cell and smooth muscle cell. Endothelin-1 and peroxyl radicals play an important role in the VC response to Aβ.