Effect of thrombin in the injury, especially on chemotaxis and accumulation of the inflammatory cells

凝血酶在损伤中的作用，特别是对炎症细胞趋化和积累的作用

• 批准号: 11671382
• 负责人: SUZUKI Michiyasu
• 金额: $ 2.24万
• 依托单位: Yamaguchi University (2000)Iwate Medical University (1999)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671382/
• 关键词: traumatic brain injury; thrombin; inflammatory cell; cytokine; chemokine; adhesion molecule; apoptosis

Thrombin is a member of serine protease family, and has been well known to have multifunctions in coagulation, inflammation, regulation of blood vessels and central nervous systems (CNS). While thrombin effects on the brain tissues in restoring from damage, it also causes the post brain damage through glial reaction and scar formation after injury.In order to elucidate the effects of thrombin on the purpose of therapeutic application, we investigated the following studies by using anti-thrombin drug, named argatroban, in a rat brain injury model, histologically :(1) Effect of thrombin on the inflammatory cells : infiltration and accumulation of inflammatory cells, especially around the small vessels through expressing the adhesion molecules on the endothelial cells, and(2) Effects of thrombin on cells comprising central nervous system : glial response, especially, of the astrocytes when excess of thrombin or inhibitor for thrombin were administered in a rat brain injury model.Result 1 … More : Thrombin inhibitor suppressed the infiltration of inflammatory cells and excessive gliosis mainly composed of vimentin-positive astroglia, but not effected on the expression of GFAP-positive astrocytes along the injured area of rat brain.Result 2 : Thrombin accelerated the infiltration of inflammatory cells and the expression of E-selectin and ICAM-1 on the endothelial cells along the edge of brain defect.Result 3 : Thrombin inhibitor suppressed the infiltration of inflammatory cells and the expression of ICAM-1 on the endothelial cells, and also suppressed the accumulation of Mac-1 positive cell along the edge of brain defect.ConclusionThrombin caused infiltration of inflammatory cells through the expression of adhesion molecules on the endothelial cells, and led to secondary brain damage after acute inflammation.Thrombin accelerated proliferation of vimentin-positive astrocytes after brain injury.Thrombin inhibitor may minimize the secondary brain damage, and promote the neural regeneration. Less

凝血酶是丝氨酸蛋白酶家族的一员，众所周知具有凝血、炎症、血管调节和中枢神经系统（CNS）等多种功能。凝血酶在影响脑组织损伤恢复的同时，也通过损伤后的胶质反应和疤痕形成引起脑损伤。为了阐明凝血酶在治疗应用中的作用，我们使用抗凝血酶药物阿加曲班在大鼠脑损伤模型中进行了以下组织学研究：（1）凝血酶对炎症细胞的影响：炎症细胞的浸润和积累， (2) 凝血酶对中枢神经系统细胞的影响：在大鼠脑损伤模型中给予过量凝血酶或凝血酶抑制剂时，尤其是星形胶质细胞的神经胶质反应。结果 1 …更多：凝血酶抑制剂抑制炎症细胞的浸润和过度的神经胶质细胞增生，主要由 波形蛋白阳性星形胶质细胞，但不影响大鼠脑损伤区GFAP阳性星形胶质细胞的表达。结果2：凝血酶加速炎性细胞的浸润以及脑缺损边缘内皮细胞上E-选择素和ICAM-1的表达。结果3：凝血酶抑制剂抑制炎性细胞的浸润和脑缺损边缘内皮细胞上ICAM-1的表达。 结论凝血酶通过内皮细胞上粘附分子的表达引起炎症细胞浸润，导致急性炎症后继发性脑损伤。凝血酶加速脑损伤后波形蛋白阳性星形胶质细胞的增殖。凝血酶抑制剂可以最大程度地减少继发性脑损伤， 并促进神经再生。较少的

项目成果

Suzuki Michiyasu: "Increased levels of nitrite/nitrate in the cerebrospinal fluid of patients with subarachnoid hemorrhage"Neurosurg Rev. No22. 96-98 (1999)

Suzuki Michiyasu：“蛛网膜下腔出血患者脑脊液中亚硝酸盐/硝酸盐水平升高”Neurosurg Rev. No22。

鈴木倫保: "Argatrobanの脳血管攣縮予防効果"脳血管攣縮. 14. 350-353 (1999)

铃木道吉：“阿加曲班对脑血管痉挛的预防作用”《脑血管痉挛》14. 350-353 (1999)。

鈴木倫保: "重症クモ膜下出血の術後管理-ドレナージ・外減圧・バルビツレート-"脳循環代謝. 12(1). 1-5 (2000)

Michiyoshi Suzuki：“严重蛛网膜下腔出血的术后处理 - 引流、外部减压、巴比妥类药物 -”《脑循环与代谢》12(1) (2000)。

Suzuki Michiyasu: "Extrinsic pathway of blood coagulation and thrombin in the cerebrospinal fluid after subarachnoid hemorrhage"Neurosurgery. 44(3). 487-493 (1999)

铃木道保：“蛛网膜下腔出血后脑脊液中血液凝固和凝血酶的外在途径”神经外科。

Suzuki Michiyasu: "Prophylactic effeect of argatroban for vasospasm following subarachnod hemorrhage"Vasospasm. No14. 350-353 (1999)

铃木道保：“阿加曲班对蛛网膜下腔出血后血管痉挛的预防作用”。