Stadnicka Izabela, Strzałka-Mrozik Barbara, Solarz Krzysztof, Stadnicki Antoni
SP ZOZ Szpital Mswia w Lublinie, Lublin, Polska.
Zakład Biologii Molekularnej Katedry Biologii Molekularnej, Wydział Farmaceutyczny z Oddziałem Medycyny Laboratoryjnej wW Sosnowcu, Śląski Uniwersytet Medyczny w Katowicach, Sosnowiec, Polska.
Wiad Lek. 2018;71(8):1615-1620.
Kallikreins cleave kininogens to release kinins. Kinins exert their biological effect by activating constitutive bradykinin receptor-2 (BR2) and inducible by inflammatory cytokines bradykinin receptor-1 (BR1). Studies in animal models and some clinical observations indicate tat the activation of kallikrein - kinin system may have relevance to central nervous system (CNS) diseases, including multiple sclerosis, Alzheimer's disease, epilepsy as well as cerebral ischemia and neoplasmatic tumors. The actions of kinins include vasodilatation and increased vascular permeability may contribute to blood-brain barrier disruption. Kinins evoke pain, and stimulate of endothelial cells, white blood cells, astrocytes and microgia cells to release of prostanoids, cytokines, free radicals, nitric oxide. Kinins stimulate angiogenesis and proliferation of tumor cells. These events lead to neural tissue damage and long lasting disturbances in blood-brain barrier function. In animal models the overexpression of genes and proteins of tissue kallikrens, kininogen as well as RB1 and RB2 has been observed. Kinin receptors antagonists, especially B1R blockade decreased morphological and biochemical features of CNS inflammation. On the other hand in brain tumor models RB1 and RB2 activation has been shown to mediate reversible blood-brain barrier permeability to enhance anti-cancer drug delivery, which may have therapeutic potential.
激肽释放酶可裂解激肽原以释放激肽。激肽通过激活组成型缓激肽受体-2（BR2）发挥其生物学效应，并可被炎性细胞因子诱导激活缓激肽受体-1（BR1）。动物模型研究和一些临床观察表明，激肽释放酶-激肽系统的激活可能与中枢神经系统（CNS）疾病有关，包括多发性硬化症、阿尔茨海默病、癫痫以及脑缺血和肿瘤。激肽的作用包括血管舒张和血管通透性增加，这可能导致血脑屏障破坏。激肽可引起疼痛，并刺激内皮细胞、白细胞、星形胶质细胞和小胶质细胞释放前列腺素、细胞因子、自由基、一氧化氮。激肽可刺激血管生成和肿瘤细胞增殖。这些事件会导致神经组织损伤和血脑屏障功能的长期紊乱。在动物模型中，已观察到组织激肽释放酶、激肽原以及RB1和RB2的基因和蛋白过表达。激肽受体拮抗剂，尤其是B1R阻断剂可减轻CNS炎症的形态学和生化特征。另一方面，在脑肿瘤模型中，已证明RB1和RB2的激活可介导血脑屏障的可逆通透性，以增强抗癌药物的递送，这可能具有治疗潜力。
