【摘要】 以¹⁴C 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。更多还原

【Abstract】 The antifertility effect of gossypol was discovered and confirmed by Chinese Scientific workers during therecent years through experiments onanimals and clinical studies.However,It’s toxicity to animals and the develop-ment of side effects in some of thesubjects following gossypol administra-tion have also been reported.In orderto analyze the cause and effect rela-tionship between the toxicity and thenature of metabolism of gossypol,wehave conducted experiments designedto obtain information concerning themetabolic fate of gossypol in rats fol-lowing the oral administration of ¹⁴C-gossypol acetic acid.Wistar male rats selected for uniformity of weight （105—200g body weight） were placed in individual metaboliccages that were designed to controlexperimental conditions.A single oraldose （94μci/35mg） of radioactive gos-sypol （sp.act.2.665μci/mg） was givento each rat in one group of experi-ments,and in another group the ratswere given labeled gossypol at thedosage of 4.5μci/5mg/day for 2—3 weeksconsecutively.The rats were anesthetized and frozen in acetone cooled to-78℃ with dry ice after varying intervals of time.Whole body andmicro-autoradiography of various or-gan tissues were performed according tothe methods described elsewhere.Ob-servations on the absorption,distribu-tion,accumulation and elimination of¹⁴C-gossypol in the rat body as wellas cytopathological examination on theH.E.stained histological sections werecarried out.（1） The whole-body autoradio-graphs demonstrated that the radioac-tivity was located mainly over thegastro-intestinal tract and liver,andthe contents of different parts of the alimentary canal had the highest acti-vity 1-2 days following a single oraldose of ¹⁴C-labeled gossypol.At thefourth day,there was a general increasein the activity in all tissues,and theradioactivity in the main visceral organswere rapidly reached to their highestlevel by the 9th day.Strong accumu-lation could be observed in the liver,spleen,kidney,adrenal,pancreas,mu-scle,lymph node,thymus,pitutary,testis and salivary gland in the 9th day autoradiograph.14 days after the administration,the radioactivity in alltissues and organs were markedly de-creased,Only in bones and lymphnodes still contained high activities.Most of the tissues had no detectableor having very low activity 19 daysafter the oral dosing,indicated that nolong term accumulation of gossypolretained in the visceras.（2） The pattern of absorption anddistribution of radioactivity in the bodyof rats that on continuous administra-tion of ¹⁴C-gossypol （4.5μci/5mg/day）was basically similar to the rats thatreceived a single oral dose.In both dosage cases,the alimentary canaland liver had the highest activity,followed by the spleen,lymph nodes,heart,kidney,adrenal,bone marrow,salivary gland,thymus,muscle,testis,epididymis,accessory sex glands,pan-creas,lung and urinary bladder inwhich decreased their radioactivitiesin order.Gossypol was usually unde-tectable in the brain and spinal cordor having the lowest activity only,evidently there was blood-brain barrier that protected the brain against passage of gossypol.（3） The organs concerned withelimination of gossypol,spleen,lymphnode,thymus,bone marrow as well asthe reticulo-endothelial cells of variousvisceral organs （i.e.Kupffer cells ofliver,dust and septal cells of lung,lymphocytes,plasma cells and macro-phages in different tissues） showed highconcentrations of radioactivity,sugges-ted that the reticulo-endothelial systemmight play a part in the detoxicationof gossypol in the body.（4） Cytological examination reve-aled that,with the exception of thetestis,no pathological changes weredetectable in the organs and tissuessuch as liver,spleen,heart,kidney,lung,pancreas and bone marrow.Thefact that the testis is the only organthat is damaged at low dosage of gos-sypol and that the radioactivity in thetestis is lower than that in the aboveorgans indicates that the selective orhigher susceptibility of the testis togossypol is not due to concentration ofgossypol in the testis,but to a highervulnerabilit sensitivity of the testis to the drug. （5） The results revealed that there was rather high radioactivity in the endocrine organs concerned with re- production and water and salts metabo- lism （i.e.adrenal gland,pituitary andthe Leydig cells of interstitial tissuesof testis）,and a significant but lowamounts of radioactivity in the nucleiof hypothalamus as well as the medianeminence,suggests the possibility thatgossypol might effect in some degreeon the above endocrine hormone secre-tions and on the autonomic nervouscenter as well.（6） The possible cause and effectcorrelation between the clinical sym-ptoms （i.e.The transient weakness,SGPT and ECG changes,hypokalemicand thirsty etc.） and gossypol adminis-tration in connection with the distribu-tion of ¹⁴C-gossypol in high amountsin the corresponding tissues and organssuch as skeletal muscle,liver,heart,kidney and salivary gland in this reportwas discussed.更多还原