【作者】 涂彧；

【导师】 朱寿彭；

【作者基本信息】 苏州大学 ， 放射医学， 2002， 博士

【摘要】 目的：观察人脑胶质瘤SHG44细胞对不同浓度的³²P-磷酸钠和³²P-磷酸铬的摄取；探讨不同浓度³²P-磷酸钠和³²P-磷酸铬对SHG44细胞生长的抑制；揭示³²P-磷酸钠和³²P-磷酸铬在大鼠颅内注射在时全身主要脏器的蓄积与排除规律；观察³²P-磷酸铬大鼠颅内瘤体、皮下瘤体内注射的治疗效果；估算大鼠瘤体组织的吸收剂量；观察³²P照射引起的细胞及组织的病理学改变，为临床脑胶质瘤内照射治疗提供实验依据和吸收剂量计算方法。 方法：以不同浓度(³²P-磷酸钠培养液终浓度为0.006，0.012，0.018，0.024，0.036，0.072，0.089，0.178，0.356MBq/ml，³²P-磷酸铬培养液终浓度为0.013，0.026，0.052，0.104，0.208，0.416MBq/ml)培养SHG44细胞48h，中止培养（中止前12小时加入³H-TdR），收获细胞，液闪测定³²P、³H的放射性活度（以dpm表示，下同）；SHG44细胞在³²P-磷酸钠为0.093MBq/ml、³²P-磷酸铬为0.104 MBq/ml的培养液中分别培养，（1.5,3,6,12,24,48,96h）后，中止与³²P药液的接触，继续培养至48h，96h组培养至96h，中止培养前12h加³H-TdR，收获细胞，液闪测定³²P dpm、³H dpm；以终浓度为0,0.037,0.093,0.185,0.370,0.925，1.850 MBq/ml的³²P-磷酸钠培养液，终浓度为0,0.052,0.104,0.208,0.417,0.834,1.668 MBq/ml的³²P-磷酸铬培养液，培养SHG44细胞48h，取2000个细胞，平皿接种，培养14天，计数细胞集落；用微量注射器向一组大鼠颅内注射50111计3．145MBq 32p．磷酸钠，向另一组注射50μl计2.886MBq³²P-磷酸铬，于注射后20分钟至16天，在不同的时间处死大鼠，取血液、心、肝、脾、肺、肾、大脑、股骨头及睾丸等组织，制备均相液体闪烁测量样品，测定各组织的³²Pdpm；对颅内及皮下荷瘤成功的大鼠分别进行瘤体内注射³²P-磷酸铬，颅内瘤为4.07MBq，皮下瘤为18.5MBq，观察大鼠存活时间，体重变化；计算颅内瘤、皮下瘤的吸收剂量；分别制作治疗组与对照组的组织及细胞的病理切片与电镜切片。’中内照射脑胶质瘤的实验治疗研究 中英文摘要结果：随着培养液卫p．磷酸钠／zp．磷酸铬浓度的增加，SHG44细胞的℃p dpm增高。相应的‘H dpm下降；随着与 32P－磷酸钠、32P－磷酸铬接触时间的延长，SHG44细胞的HP dpm增高，相应的‘H dpm下降：3中－磷酸钠对细胞集落形成抑制程度大于HP－磷酸铬；经颅内注射后，HP．磷酸钠、卫P－磷酸铬在大鼠体内有明显不同的蓄积与清除规律，3中．磷酸钠在大鼠体内的迁移程度比 32p．磷酸铬高出 2个数量级；32p．磷酸铬瘤体内注射可明显延长颅内荷瘤大鼠的生存时间，改善皮下荷瘤大鼠的生存质量；4刀7MBq的 3中磷酸铬注入大鼠颅内后，在大鼠头部最终产生 190Gy的吸收剂量，18．SMBq的卫P－磷酸铬注入大鼠皮下瘤体后，最终产生 350Gy的吸收剂量，等效于临床胶质瘤常规外照射分割照射每次工88Gy，与临床实用剂量2刀Gy十分接近；瘤体病理切片可见32P有明显的加速肿瘤组织变性坏死的作用，电镜下可见肿瘤组织内出现凋亡细胞。结论：对于体外肿瘤细胞而言尸中－磷酸钠有较卫中．磷酸铬更好的杀伤力；而在荷瘤机体中，卫P－磷酸铬对肿瘤组织有更集中的选择性滞留，可更好地杀伤肿瘤组织细胞，保护正常组织。通过对肿瘤组织吸收剂量的计算，可以寻找出更符合实际病情的、更适宜的 32P－磷酸铬用量。更多还原

【Abstract】 Purposes: To observe intakes of P-sodium-orthophosphate and P-chromium-orthophosphate at various concentrations by brain gliomas cell; To make thorough inquiry of the inhibition to the SHG44 cell by 32P-sodium-orthophosphate and 32P-chromium-orthophosphate at various concentrations; To find out the regularities about the accumulation and elimination in the major organs of rats after inter-brain injection with 32P-sodium-orthophosphate and 32P-chromic-orthophosphate; To investigate the therapeutic effects of intert-injection with 32P-chromium-orthophosphate on the neoplasia transplanted in the brain and hypoderma; To estimate the absorbed dose of the neoplasia body in rats after internal radiation; To study the pathological changes in the rat cells and tissues caused by the radiation exposure from 32P. In order to provide experimental evidence and calculating method of absorbed dose for the internal radiation therapy of gliomas.Method: Cultivated SHG44 cell at various concentrations (the ultimate concentrations of 32P-sodium orthophosphate culture medium were 0.006, 0.012, 0.018, 0.024, 0.036, 0.072, 0.089, 0.178, 0.356MBq/ml respectively for 48 hours , the ultimate concentrations of 32P- chromium-orthophosphate culture medium were 0.013, 0.026, 0.052, 0.104, 0.208, 0.416MBq/ml respectively), then cultivation was broken off and the cells were harvested (3H-TdR was added 12 hours before breaking off cultivation), Determination of specific activity of 32P and 3H was performed by liquid scintillation counting(The results were expressed in dpm, the same below); SHG44 cell was cultivated in ^P-sodium-orthophosphate and 32P-chromic-orthophosphate culture media with concentrations of 0.093MBq/ml and 0.104MBq/ml for different times(1.5, 3, 6, 12, 24, 48, 96hr), After suspending of contact with 32P, Cultivating was continued until 48 hours for the former 6 groups’, the 96 hours’ group 96 hours, The cells were harvested (3H-TdR was added 12 hours before breaking off cultivation), The determination of specific activity of 32P dpm and 3H dpm were carried out with homogenous liquid scintillation counting; SHG44 cellwas cultivate for 48 hr by 32P-sodium-orthophosphate or 32P-chromic-orthophosphate culture media respectively whose ultimate concentrations for the former were 0, 0.037, 0.093, 0.185, 0.37, 0.925, 1.85 MBq/ml and for the latter were 0, 0.052, 0.104, 0.208, 0.417, 0.834, 1.668MBq/ml, Afterwards, 2000 cells from the culture media were taken out and transplanted in the agar-culture-medium-plate and cultivated for 14 days, The numbers of cell colonies were counted; The solution of 50Ml(containing 3.145MBq 32P-sodium-orthophosphate) was injected into rats’ brain of one group with a microsyringe, The solution of 50Ml(contammg 2.886 MBq 32P-chromium- orthophosphate) was injected into another group. Then the rats were killed at different time ranging from 20 minutes to 16 days, Their blood, heart, liver, spleen, lung, kidney, cerebrum and testis were sampled and made homogeneous samples which can be dosimetry by liquid scintillation counting, the specific activity of 32P dpm in each tissue was measured; The rats that were successfully transplanted with gliomas in the brain and hypoderma were given inter-glioma injection with 32P-chrornium-orthophosphate (for the rats with transplanted brain glioma were given 4.07MBq, for the rats with transplanted hypodermic tumors 18.5MBq). Their survival time and the changes of weight were observed; The absorbed dose of the brain and hypodermic neoplasia were calculated; The pathological sections and electron microscope sections of the tissues from both the therapy group and the controls group were made.Results: With the increase of the concentrations of both 32P-chromium- orthophosphate and 32P-sodium-orthophosphate in culture media the specific activity (dpm) of 32P in SHG44 cell elevated, at the same time the specific activity (dpm) of 3H decreased; with the lengthening of contact time with 32P-chromium-orthophosphate or 32P-sodium-orthophosphate, the specific activity (dp更多还原