托吡酯对Lewis肺癌转移的抑制作用与水通道蛋白1的关系

AIM: To study the effect of topiramate on tumor metastasis and its relation with aquaporin 1 (AQP1) water channel. METHODS: Lewis lung carcinoma metastatic model was used to determine the effect of topiramate on tumor growth and metastasis. Colorimetric estimation was used to investigate the action of topiramate on carbonic anhydrase (CA) activity. Western blotting and immunohistochemical analysis were used to study the influence of topiramate on AQP1 water channel expression in lungs or tumor tissues of mice bearing Lewis lung carcinoma.cantly (P＜0.05). Its inhibitory rate of metastasis was 81.25 %. Topiramate inhibited CA activity in lungs of mice in a dose-dependent manner. Topiramate apparently decreased AQP1 protein expression and immunostaining in lungs or in tumor microvessel endothelial cells of mice. CONCLUSION: Suppression of AQP1 water channel expression may be an important pathway for the inhibitory effect of topiramate on tumor metastasis.

乙酰唑胺和anordiol对注射水通道蛋白1-cRNA的爪蟾卵母细胞渗透水通透性的影响

AIM: To study the effects of acetazolamide and anordiol on osmotic water permeability in aquaporin 1 (AQP1)-cRNA injected Xenopus oocyte and their mechanisms. METHODS: AQP1 gene constructed in pBluescript was transcripted into cRNA in vitro and then the cRNA was injected in Xenopus oocytes. The effects of acetazolamide and anordiol on the water transport function of AQP1 were observed by assaying the osmotic swelling of oocytes.In addition, their effects on protein expression of AQP1 were quantitatively investigated by Western blotting method.RESULTS: After incubation for 15 min or 72 h, acetazolamide, a carbonic anhydrase inhibitor, equally reduced the water permeability of AQP1-cRNA injected oocyte in a dose-dependent manner. After incubation for 72 h, anordiol,an antiestrogen with partial estrogenic activity, reduced the osmotic water permeability dose dependently as well;however, no discernable action was observed after incubation with anordiol for 15 min. The Western blotting analysis showed that acetazolamide did not influence the protein expression of AQP1. However, after incubation for 72 h with anordiol (10 μmol/L), the quantity of AQP1 in the oocyte membrane was decreased dramatically (P＜0.05). CONCLUSION: Both acetazolamide and anordiol inhibited the osmotic water permeability of AQP1cRNA injected oocyte, but their mechanisms were different. Acetazolamide functionally inhibited the osmotic water permeability of AQP1, whereas anordiol primarily decreased the amount of AQP1 protein in the oocyte membrane.

Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortal-ity following traumatic brain injury as it increases intracra-nial pressure, impairs cerebral perfusion and oxygenation,and contributes to additional ischemic injuries.Classically,two major types of traumatic brain edema exist: "vasogenic"and "cytotoxic/cellular".However, the cellular and molecu-lar mechanisms contributing to the development/resolution of traumatic brain edema are poorly understood and no ef-fective drugs can be used now.Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, pre-dominantly in astrocyte foot processes at the borders be-tween the brain parenchyma and major fluid compartments, including cerebrospinal fluid and blood.This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma.In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma.AQP4 has been proposed as a novel drug target in brain edema.These findings sug-gest that modulation of AQP4 expression or function may be beneficial in traumatic brain edema.