饱和转铁蛋白和凝血酶在脑出血后早期脑损伤中的作用

目的探讨脑出血后早期脑组织中铁的来源及其损伤机制，观察是否存在另一种铁相关血液成分如饱和转铁蛋白（holo—Tf），它和凝血酶也可能参与脑出血后早期的脑损伤。方法在雄SD大鼠右侧大脑基底核分别注入holo—Tf、游离转铁蛋白（apo—Tf）、小剂量凝血酶、凝血酶与apo—Tf复合物以及凝血酶与holo—Tf复合物。24h后观察脑水肿情况，鉴定DNA破坏（免疫组化测定8-羟基-2-脱氧乌苷）和铁分布（三价铁染色测定）情况。结果hoio—Tf、apo—Tf和1u凝血酶单独注射都不能导致脑水肿，而holo—Tf和凝血酶复合物能导致明显脑水肿（P〈0．05）、DNA破坏和同侧基底核铁的蓄积。结论在脑出血后早期（24h内）的确存在铁介导的脑损伤，它与血红素降解产物之一的铁离子无关。主要作用机制可能是holo—Tf和小剂量凝血酶导致脑出血后脑损伤，而凝血酶可能通过促进细胞内铁摄取来加重脑损伤。

Holo-transferrin and thrombin are involved in brain damage after intracranial hemorrhage

Objective To investigate the involvement of holo-transferrin （holo-Tf） in brain tissue damage after intracranial hemorrhage （ICH）. Methods Male Sprague-Dawley rats received an intracerebral infusion of holo-Tf, apo （noniron-loaded）-Tf, thrombin, or a combination of Tf with thrombin into the right basal ganglia. The rats were euthanized 24 h later for measurement of brain edema and assessment of DNA damage （by 8-hydroxyl-2-deoxyguanosine immunohistochemistry）. Iron distribution was examined by iron dyeing. Results Holo-Tf, apo-Tf, or thrombin did not induce brain edema when administered alone. The combination of holo-Tf with thrombin caused brain edema （P〈0.05）, DNA damage, and intracellular iron accumulation in the ipsilateral basal ganglia. Conclusion Results suggest that Tf-bound iron may contribute to ICH-induced brain injury and thrombin may facilitate cellular iron uptake.