棉酚对大鼠胆汁谷胱甘肽含量的影响

<正> de Peyster等证明棉酚与大鼠肝微粒体及人精子体外温育能产生自由基,推测可能是棉酚生物活性的基础。新近报道右旋(+)及左旋(-)棉酚(gossypol,G)体外与大鼠肝及肾微粒体温育能产生自由基。但自由基的生成是否为棉酚抗生育以及血清谷丙转氨酶(ALT)升高的毒性机理,值得进一步探讨。     

(-)和(+)棉酚对雄大鼠生育力的影响

Racemic, (-) and (+) gossypol, provided by the Department of Organic Chemistry of our institute, was suspended in 2.5% tween 80 solution. Adult male Wistar rats 190～220 g in weight were allotted to 5 groups. Animals in group 1 received 2.5% tween 80 solution as control. Rats in group 2 were treated with racemic gossypol at the dosage of 30 mg/kg for 2 weeks. Animals in group 3 and 4 were given 15 mg/kg of (-) gossypol for 2 weeks and 30 mg/kg of (-) gossypol for 1 week respectively. Rats in group 5 were treated with (+) gossypol at the dosage of 30 mg/kg for 2 weeks.Four weeks from the beginning of gossypol treatment the rats were cohabited with adult females for 7 days. Then the motility of the sperms in the cauda epididymides was estimated The female rats were examined for pregnancy 7 days later.Treatment with (-) gossypol at 30 mg/kg caused significant decreases in body weight of the rats (P<0.05). One of the five rats died 7 days after the last administration, while (+) gossypol and racemic gossypol at the dosage employed had no effect on the body weight. (+) Gossypol at 30 mg/kg for 2 weeks had no effect on the motility of the sperms in the cauda epididymides and no effect on the fertility of the animals: nor was there any effect on the weights of the testis, epididymis, prostate and seminal vesicle. The sperms of the cauda epididymides were found to be dead in the groups treated with 15 and 30 mg/kg of (-)gossypol. Raccmic gossypol given for 2 weeks at 30 mg/kg caused loss of fertility of the male rats which confirmed our previous findings.(?)t may be postulated that (+) gossypol has no antifertility effect nor toxicity at the dosage employed. (-) Gossypol is the active stereoisomer of racemic gossypol.     

(-)和(+)棉酚对雄大鼠生育力的影响

棉酚有明显的抗雄性生育作用,但在理论上尚不清楚消旋棉酚的抗生育作用和毒性来自那一种光学异构体。已有报告指出(+)棉酚无毒无效。但对(-)棉酚的研究迄今尚未有报道。本文应用本所合成室制备之(+)和(-)棉酚,观察了他们的抗生育作用。实验用Wistar雄大鼠(190～220g)25只,分为对照,(+)棉酚30mg/kg,(-)棉酚15和30 mg/kg以及消旋棉酚30 mg/kg等5组。每天喂药1次,(+)棉酚和(-)棉酚     

醋酸棉酚对子宫和卵巢的影响

Gossypol has been employed in gynecologic clinics for the treatment of endometriosis and functional uterine bleedings with encouraging results. In the present communication the effects of gossypol on the uterus and ovary were studied both experimentally and clinically by histologic and histochemical techniques. It was found that treatment of female rats with gossypol acetic acid at 30 mg/kg/d, six days a week, for 8 weeks caused marked atrophy of the endometrium and a reduction of the glycogen content of the myometrium. Vaginal smears showed a picture of atypical estrous cycle. Simultaneous administration of 1 mg/kg/d of estriol reduced the effect of gossypol acetic acid though the influence of gossypol treatment was still discernible. Treatment of 16 patients suffering from endometriosis or functional uterine bleeding with gossypol acetic acid for 2-3 months induced changes similar to those observed in animal experiments, namely, atrophy of the endometrium and decrease in endometrium glycogen. In 3 other patients treated with gossypol acetic acid for 4～5 months there was a slight increase in Sudan Black B staining and a decrease in alkaline phosphatase, acid phosphatase, PAS staining and RNA of the endometrium. There was also a change of biphasic basal body temperature into monophasic and a lowered estrogen level as revealed by vaginal cytology.One may speculate from the above results that gossypol may act on the uterus directly as well as indirectly through inhibition of the secretory function of the ovary and/or through antagonism against the effect of estrogens in the female. Hence, it may be desirable to conduct further studies on the effect of gossypol on the pituitary-gonadal axis.     

醋酸棉酚对子宫和卵巢的影响

本文用组织学和组织化学的方法,观察了经醋酸棉酚治疗后雌性大鼠子宫内膜和卵巢的变化,同时也研究了某些妇科病人棉酚治疗后子宫内膜的改变。     

棉酚及其衍生物药理作用研究概述

棉酚（gossyp01）又称棉籽醇，是一种天然存在于锦葵科的黄色酚类化合物，化学名为2，2＇-双-8-甲酸基1，6，7-三羟基-5-异丙基-3-甲基萘，相对分子质量518（分子式：C30H30），它是以1，1’，3，3’取代的2，2’联萘为骨架的化合物，棉酚结构中连接两个萘环的化学键不能自由旋转^[1]，具有旋光性。人口服棉酚后胃肠道吸收缓慢，主要经小肠与胃上皮吸收，大部份分泌至胆汁，有明显的肝肠循环。     

消旋棉酚拆分的研究——Ⅲ.胺缩棉酚理化性质的研究

本文报道消旋棉酚与15种不同结构的光学活性胺缩合产物的薄层色谱性质和核磁共振氢谱数据,以及8个光学活性胺与光学活性棉酚缩合物的光学稳定性,并探讨了结构与这些性质的关系。     

消旋棉酚拆分的研究——Ⅲ.胺缩棉酚理化性质的研究

本文报道消旋棉酚与15种不同结构的光学活性胺缩合产物的薄层色谱性质和核磁共振氢谱数据,以及8个光学活性胺与光学活性棉酚缩合物的光学稳定性,并探讨了结构与这些性质的关系。     

单醛棉酚及其类似物的合成

为了对具有较好抗男性生育作用的棉酚进行结构改造、简化分子、降低毒性。以醋酸棉酚或苯胺棉酚为原料合成了单醛棉酚等5个单醛型棉酚类似物,并进行了初步的体外杀精子试验,发现其中单醛棉酚的20秒杀精子活性高于棉酚5倍。     

(-)棉酚和(+)棉酚对蛋白激酶C及蛋白激酶A活力影响的比较

部分纯化的大鼠肝脏蛋白激酶C和蛋白激酶A,在体外与棉酚的旋光异构体分别温育,结果(--)棉酚和(+)棉酚对蛋白激酶C活力均有剂量依赖性的抑制作用;(-)棉酚对Ⅰ型蛋白激酶A活力的抑制作用明显比(+)棉酚强,而(-)棉酚和(+)棉酚在高浓度时对Ⅱ型蛋白激酶A才显示抑制作用。结果提示棉酚在体内可能干扰细胞信息的传递过程。     

左旋棉酚对人鼻咽癌细胞凋亡的影响

目的探讨左旋棉酚对人鼻咽癌细胞株CNE2凋亡的影响及其机制。方法采用MTT实验检测左旋棉酚对CNE2细胞的增殖抑制作用,流式细胞术分析左旋棉酚诱导细胞凋亡及其对Bcl-2、Bax蛋白表达的影响,caspase-3分光光度法检测试剂盒测定caspase-3活性。结果≥10μmol／L左旋棉酚可显著抑制CNE2细胞增殖,并表现出剂量、时间依赖效应。左旋棉酚可调节CNE2细胞的细胞周期,使其主要被阻滞于G0／G1期,在诱导细胞凋亡过程中,凋亡相关基因Bcl-2表达下降,而Bax表达则相对上调,caspase-3活性在24h达到高峰。结论左旋棉酚在体外可诱导鼻咽癌细胞CNE2凋亡,其机制可能与Bcl-2基因下调、Bax基因上调、caspase-3的激活有关。     

醋酸棉酚对雌性大鼠的抗早孕作用

大鼠于妊娠第6～9天,喂以醋酸棉酚80 mg/kg/d, 有明显的抗早孕作用。皮下注射孕酮5 mg/d或hCG 25 IU/d可拮抗醋酸棉酚的抗早孕作用。醋酸棉酚80 mg/kg/d对去卵巢后给以外源性雌酮和孕酮以维持妊娠的大鼠无抗早孕作用。正常妊娠大鼠,给醋酸棉酚后,血清孕酮水平下降,妊娠中止,若同时注射hCG,孕酮水平回升接近对照动物的水平,药物抗早孕作用消失,但仍低于单给hCG组大鼠血清孕酮水平,说明醋酸棉酚可阻断hCG促黄体分泌孕酮的作用,这可能是醋酸棉酚抗早孕作用的主要机理之一。     

棉酚的极谱研究

本文介绍了棉酚的极谱测定方法。棉酚在柠檬酸—磷酸氢二钠缓冲液中可产生一还原波,在pH值为2.60时,其E_1/2为-1.14 V(SCE)。实验证明该波为受扩散控制的单电子可逆波,推测为棉酚芳醛基之一的单电子还原。所建立的方法较简便、快速、灵敏。     

棉酚的极谱研究

本文介绍了棉酚的极谱测定方法。棉酚在柠檬酸—磷酸氢二钠缓冲液中可产生一还原波,在pH值为2.60时,其E_(1/2)为-1.14 V(SCE)。实验证明该波为受扩散控制的单电子可逆波,推测为棉酚芳醛基之一的单电子还原。所建立的方法较简便、快速、灵敏。     

醋酸棉酚长期给药的进一步观察

给成年雄性大鼠每日服醋酸棉酚10 mg/kg,每周服6天。服6个月后进行病理和组织化学观察。结果说明给醋酸棉酚大鼠各主要脏器(心、肝、脾、肺、肾、肾上腺)的形态都没有明显变化。组织化学观察说明,给棉酚大鼠的肝脏油红“O”染色、G-6-P酶、ATP酶、ALP酶、ACP酶、糖原、RNA和DNA肾脏G-6-PDH、油红“O”染色、ATP酶、ACP酶、ALP酶;肾上腺3β-甾体脱氢酶、油红“O”染色、苏丹黑染色等与对照组比较都没有明显差别。     

棉酚单侧衍生物的合成及其口服抗生育活性研究

本文报道单醛棉酚和单苯胺棉酚合成工艺的改进,即采用新的有效的分离方法,提高收率,从而首次完成了这两个化合物的雄性大鼠口服抗生育实验。文中还首次报道了单醛棉酚的mp,UV,IR,MS及完整的~1H-NMR数据并阐明了单醛棉酚在DMSO-d_6溶剂中同时共存着醛式与内醚式两种互变异构体。     

一苯胺棉酚—棉酚中的一种杂质

本文介绍了棉酚中的一种杂质(苯胺法精制)一苯胺棉酚的研究。该化合物文献中未见报道。实验数据符合组成式C₃₈H₃₅O₇N;质谱分子离子峰593,紫外光谱于439～440 nm有最大吸收(E_1com^1% 329±6 CHCl₃);红外光谱在1610 cm^-1有醛基和1590 cm^-1碳氮吸收峰;核磁共振谱表明有—CHO和—HC=N质子峰,其峰面积比为1:1;熔点272～275℃(分解);硅胶薄层上Rf值界于二苯胺棉酚和棉酚之间。一苯胺棉酚的存在,干扰分光光度法测定棉酚含量的准确性。利用薄层层析法可检查棉酚中一苯胺棉酚的存在与否。本文还介绍了一苯胺棉酚的合成方法。     

HPLC测定棉油皂脚中棉酚含量

目的建立高效液相色谱法测定棉油皂脚中总棉酚（TGP）与游离棉酚（FGP）含量的方法。方法采用WatersBondapak C18 Column（3.9 mm×150 mm,4μm）;流动相为乙腈-0.7%磷酸水溶液（80∶20）;流速为1.0 mL.min-1;检测波长为238 nm;柱温为25℃。结果棉酚在10～60μg.mL-1（r=0.999 4）内线性关系良好,平均加样回收率为99.03%,RSD=1.72%（n=3）。结论本法简便、快速、准确、重复性高,可用于对棉油皂脚中棉酚的含量测定。     

雷公藤多甙与棉酚合用对雄大鼠生育力的影响

本研究探讨雷公藤多甙(GTW)与棉酚合用对雄大鼠生育力的影响。SD雄大鼠用棉酚及GTW各6 mg/kg/d,灌胃给药,每周6日,共11周。10只用药动物全部不育,附睾精子密度和活率也明显下降,而体重增长如常,性行为存在。睾丸光镜下结构绝大多数无明显异常,血清睾酮水平正常,副性腺重量无明显变化。停药6周后生育力恢复。在相同剂量下,单用GTW或棉酚均无抗生育效果。表明两药合用有相加作用,为减少棉酚和GTW副作用提供一条可能途径。