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实验性脑肿瘤的区域代谢

Regional metabolism of experimental brain tumors.

作者信息

Hossmann K A, Mies G, Paschen W, Szabo L, Dolan E, Wechsler W

出版信息

Acta Neuropathol. 1986;69(1-2):139-47. doi: 10.1007/BF00687050.

Abstract

Experimental brain tumors were produced in rats by stereotactical implantation of various neoplastic cell lines (RG 2, RG1 2.2, G 13/11, F 98, RN 6, B 104, and E 367). Using autoradiographic, bioluminescence, and fluoroscopic methods, the following regional hemodynamic and metabolic parameters were measured on intact brain sections: blood flow, glucose utilization, pH, and the tissue content of ATP, glucose, and lactate. Tumors exhibited a considerable diversity of regional blood flow and metabolic activity which did not correlate with the implanted cell line, location, or growth pattern. In solid regions of tumors the most consistent finding was a higher glucose utilization rate, a higher lactate, and a higher pH than in the surrounding brain tissue. Tumor ATP was slightly higher and glucose slightly lower than in the brain. In large spherical tumors a declining gradient of blood flow, glucose, and ATP from the periphery to the central parts was frequently observed, the decline being more pronounced for glucose than for ATP. In regions with high ATP tissue pH was usually higher than in the brain, but it decreased in areas in which ATP was depleted. The results obtained indicate that tumors are able to control tissue pH despite increased glycolysis and lactate production, as long as the energy state is not impaired. The mechanisms of pH regulation, therefore, have to be considered for establishing therapeutic procedures which intend to lower tumor pH for induction of tissue necrosis.

摘要

通过立体定向植入各种肿瘤细胞系(RG 2、RG1 2.2、G 13/11、F 98、RN 6、B 104和E 367)在大鼠体内诱发实验性脑肿瘤。采用放射自显影、生物发光和荧光镜检查方法,在完整脑切片上测量以下局部血流动力学和代谢参数:血流量、葡萄糖利用率、pH值以及ATP、葡萄糖和乳酸的组织含量。肿瘤在局部血流和代谢活性方面表现出相当大的差异,这与植入的细胞系、位置或生长模式无关。在肿瘤的实体区域,最一致的发现是葡萄糖利用率、乳酸含量和pH值均高于周围脑组织。肿瘤中的ATP略高于脑内,而葡萄糖略低于脑内。在大型球形肿瘤中,经常观察到从周边到中心部位血流量、葡萄糖和ATP呈下降梯度,葡萄糖的下降比ATP更明显。在ATP含量高的区域,组织pH值通常高于脑内,但在ATP耗竭的区域pH值会降低。所得结果表明,只要能量状态未受损,肿瘤尽管糖酵解增加和乳酸生成增多,但仍能够控制组织pH值。因此,在制定旨在降低肿瘤pH值以诱导组织坏死的治疗方案时,必须考虑pH调节机制。

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