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以~(14)C 标记的醋酸棉酚喂饲成年雄性大鼠,一次口服组的剂量为94微居里/35毫克;累加服药组为4.5微居里/日。分别于服药后不同时期取材制成整体或组织放射自显片。追踪标记棉酚在体内各脏器和组织中的吸收,分布和累积的定位变化动态。相应的组织切片用H、E 染色,作细胞病理学观察。结果摘述如下:1.一次口服标记棉酚后1—2天,标记物主要分布于胃、肠道和肝脏中。4—9天后,心、脾、肺、肾、胰、睾丸、附睾、附属性腺、肾上腺、垂体、胸腺、唾腺、骨髓、淋巴结和肌肉等脏器组织中的活性均迅速达到各自的高峰水平。以后标记物逐渐扩布至全身。14天后,活性明显下降。19天后,活性已不易追踪。未见有长期定位的累积现象。累加服药组的吸收和分布状态与一次服药组基本相同。2.定位于各脏器组织中的标记物活性强度以消化道为最高,其次为肝脏。以下的大体顺序为:脾、淋巴结>心、肾、垂体、肾上腺、骨髓>唾腺、胸腺、肌肉、睾丸、附睾、附属性腺、胰、肺>血液> 膀胱>脑及骨髓。骨质在后期活性略有升高。脑和脊髓的活性反应微弱,可能与血脑屏障的保护性作用有关。3.脾脏、淋巴结、胸腺、骨髓和各脏器中的网状内皮系细胞(枯否氏细胞、尘细胞、淋巴细胞、浆细胞、巨噬细胞等)均呈现高强度的放射活性。表明网状内皮系统可能参与清除棉酚的解毒过程。4.实验中出现较高活性分布的心、肝、脾、肾、肺、胰、骨髓等主要脏器组织均未见有细胞病理改变,而处于中等活性水平的睾丸曲细精管则出现明显的细胞损伤。表明生精上皮细胞对棉酚的敏感性较其他脏器组织为高。毒性反应与剂量水平在一定范围内似无正比相关,而与细胞的敏感性和耐受性的高低则有密切关系。5.与生殖及水盐代谢有关的内分泌腺:肾上腺、垂体和睾丸间质细胞均有较高的放射活性。丘脑下部有关核团及正中隆突亦有微弱的活性定位。提示了棉酚在某种条件下对上述内分泌激素分泌及植物性神经中枢产生影响的可能性。6.本报导联系临床上出现的口干、乏力及过渡性肝功能和心电图异常等毒性症状与相应脏器(唾腺、肌肉、肝及心脏)中标记棉酚活性分布的状态及其间的可能相关予以讨论。
Adult male rats fed with ~(14)C-labeled gossypol acetate had an oral dose of 94 microcuries/35 milligrams; the cumulative dose was 4.5 microcuries/day. After taking the medicine at different times, the whole body or tissue radiographs were made. Trace the dynamics of the absorption, distribution and accumulation of the marked gossypol in various organs and tissues in the body. Corresponding tissue sections were stained with H and E for cytopathological observation. The results were summarized as follows: 1. One or two days after oral administration of gossypol, markers were mainly distributed in the stomach, intestines and liver. After 4 to 9 days, the activity in heart, spleen, lung, kidney, pancreas, testis, epididymis, accessory glands, adrenal glands, pituitary, thymus, salivary glands, bone marrow, lymph nodes, and muscles quickly reached their respective peak levels. . Later, the marker gradually spread to the whole body. After 14 days, activity decreased significantly. After 19 days, activity has not been easily tracked. There is no cumulative phenomenon of long-term positioning. The absorption and distribution status of the cumulative medication group is basically the same as that of the one-time medication group. 2. The activity intensity of the marker located in each organ tissue was the highest in the digestive tract, followed by the liver. The following general order is: spleen, lymph node> heart, kidney, pituitary gland, adrenal gland, bone marrow> salivary gland, thymus, muscle, testis, epididymis, accessory gland, pancreas, lung> blood> bladder> brain and bone marrow. Bone activity slightly increased in the later period. The active reaction of the brain and spinal cord is weak and may be related to the protective effect of the blood-brain barrier. 3. Reticuloendothelial cells (Kupfer cells, dust cells, lymphocytes, plasma cells, macrophages, etc.) in the spleen, lymph nodes, thymus, bone marrow, and various organs exhibit high-intensity radioactive activity. This suggests that the reticuloendothelial system may be involved in the detoxification process of removing gossypol. 4. There were no pathological changes in the main organ tissues such as heart, liver, spleen, kidney, lung, pancreas, bone marrow, etc. with higher activity distribution in the experiment, but the testicular seminiferous tubules at a moderate activity level appeared obvious. Cell damage. It showed that the sensitivity of spermatogenic epithelial cells to gossypol was higher than that of other organ tissues. Toxicity and dose levels do not appear to be positively correlated within a certain range, but are closely related to cell sensitivity and tolerability. 5. Endocrine glands associated with reproductive and salt metabolism: Adrenergic, pituitary and Leydig cells have high radioactivity. The hypothalamus related nuclei and the median carina also have weak activity localization. The possibility of gossypol affecting secretion of these endocrine hormones and autonomic nervous centers under certain conditions was suggested. 6. This report links the clinical symptoms of dry mouth, fatigue, transitional liver function and abnormal electrocardiograms with the status of markers of gossypol activity in the corresponding organs (salivary glands, muscles, liver, and heart) and their potential. Related discussion.