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地塞米松对大鼠C6胶质瘤中¹⁴C-α-氨基异丁酸血脑和血瘤转运的时间效应

Temporal effects of dexamethasone on blood-to-brain and blood-to-tumor transport of 14C-alpha-aminoisobutyric acid in rat C6 glioma.

作者信息

Shapiro W R, Hiesiger E M, Cooney G A, Basler G A, Lipschutz L E, Posner J B

机构信息

George C. Cotzias Laboratory of Neuro-Oncology, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY.

出版信息

J Neurooncol. 1990 Jun;8(3):197-204. doi: 10.1007/BF00177352.

Abstract

We used quantitative autoradiography (QAR) to evaluate the effect of systemically administered dexamethasone on capillary permeability in brain tumors and surrounding brain. Rats bearing unilateral right hemispheric C6 gliomas were studied at one and twelve hours after 10 mg/kg of intraperitoneal dexamethasone. Capillary permeability was determined by measuring unidirectional blood-to-brain and blood-to-tumor transport of 14C-alpha aminoisobutyric acid (14C-AIB) over fifteen minutes. 14C-AIB entry into tumor, brain adjacent-to-tumor (BAT), and ipsilateral and contralateral cortices was determined and expressed as a unidirectional transfer constant, K. Nontreated tumor K was more than two-fold greater than K for BAT and ten-fold greater than ipsilateral cortical K, confirming substantial barrier disruption in tumor. In addition, the K for BAT was also significantly greater than K for cortex, indicating that the barrier in the peritumoral region was also disrupted. One hour after dexamethasone treatment, tumor K fell to 63% of its pretreatment value (p less than 0.025). By twelve hours post-treatment, tumor K fell to 25% of the untreated value (p less than 0.001) and to 47% of the one-hour value (p less than 0.005). BAT K fell to 29% of its untreated value (p less than 0.02) and to 46% of its one-hour value (p less than 0.02). By 12 hours, ipsilateral cortical K fell to 67% of the untreated cortical value (p less than 0.05). Compared to untreated values, there was no significant difference between contralateral cortical K at either one or twelve hours.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

我们采用定量放射自显影术(QAR)来评估全身给予地塞米松对脑肿瘤及周围脑组织毛细血管通透性的影响。对患有单侧右半球C6胶质瘤的大鼠,在腹腔注射10mg/kg地塞米松后1小时和12小时进行研究。通过测量15分钟内14C-α-氨基异丁酸(14C-AIB)从血液到脑和从血液到肿瘤的单向转运来测定毛细血管通透性。测定14C-AIB进入肿瘤、肿瘤邻近脑区(BAT)以及同侧和对侧皮质的情况,并将其表示为单向转运常数K。未治疗的肿瘤K值比BAT的K值大两倍多,比对侧皮质K值大十倍,这证实了肿瘤中存在明显的屏障破坏。此外,BAT的K值也显著高于皮质的K值,表明肿瘤周围区域的屏障也被破坏。地塞米松治疗1小时后,肿瘤K值降至治疗前值的63%(p<0.025)。治疗后12小时,肿瘤K值降至未治疗值的25%(p<0.001),降至1小时值的47%(p<0.005)。BAT的K值降至未治疗值的29%(p<0.02),降至1小时值的46%(p<0.02)。到12小时时,同侧皮质K值降至未治疗皮质值的67%(p<0.05)。与未治疗值相比,对侧皮质K值在1小时和12小时时均无显著差异。(摘要截短至250字)

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