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。     

棉酚对大鼠睾丸组织环一磷酸腺苷含量的影响

棉酚抗生育作用的机理国内外已有不少研究报导。国内王振刚等曾观察到棉酚对大鼠血浆 cAMP(环一磷酸腺苷)和 cGMP(环一磷酸乌苷)没有影响;而睾丸组织 cAMP 含量增加。为此,我们采用大剂量醋酸棉酚和较长时间给药对大鼠睾丸组织 cAMP 含量进行研究。     

棉酚对雄性大鼠睾酮生成的影响

给大鼠喂服醋酸棉酚每日30mg/kg,6或8wk后用放射免疫法测定血清、睾丸间质细胞液和曲精细管液中睾酮的浓度;用放射配体结合法测定睾丸中黄体生成素(LH)和卵泡刺激素(FSH)受体的含量。结果表明在上述剂量和给药时间的条件下,棉酚对垂体-睾丸轴系无影响。     

三氧化二砷对大鼠睾丸细胞酶的作用

目的:探讨药理浓度的三氧化二砷(As2O3)对雄性大鼠血清睾丸酶及精子生成的影响.方法:不同剂量的As2O3(2mg·kg-1·d-1,4 mg·kg-1·d-1和8 mg·kg-1·d-1)给予大鼠腹腔内注射,2周后检测大鼠血清睾丸酶的含量,同时,测定大鼠血清砷的含量、睾丸脏器系数、睾丸精子头计数,并计算每日精子生成量.结果:中剂量组各种酶都有所下降,G-6-PD、LDH及LDH-X的减少有统计学意义(P＜0.01,P＜0.01和P＜0.05);大剂量组ACP、ALP、G-6-PD、LDH及LDH-X均明显下降(P＜0.01).随着给大鼠腹腔注射的As2O3浓度增加,血中砷浓度明显增加(P＜0.01).3种剂量组的睾丸脏器系数与对照组差异均无显著性(P＞0.05),大剂量组睾丸精子头数和每克睾丸每日精子生成量与对照组比较减少明显(P＜0.01),血清砷含量与大鼠精子头数之间呈直线负相关(r=-0.515,P＜0.01).结论:As2O3对睾丸酶的抑制,影响了睾丸精子的生成而导致雄性生殖毒性.     

醋酸棉酚对大鼠睾网液中K~+、Na~+及睾酮水平的影响

成年雄鼠给予15mg/kg/d醋酸棉酚,连续50d灌服,导致不育,精子生成与附睾精子活力都受到明显影响。但血清与睾网液中K~+、Na~+、睾酮水平与对照组相比无明显变化。因此认为给予较低剂量的醋酸棉酚灌服大鼠,可以阻断生精作用而达到抗生育效果,但并不影响K~+、Na~+与睾酮在睾丸中分泌与转运。     

眼镜蛇神经毒素分离纯化及其经大鼠直肠给药吸收的实验研究

目的 利用色谱技术从眼镜蛇粗毒中分离纯化神经毒素,探索神经毒素经大鼠直肠途径给药后的吸收情况和镇痛活性。方法 通过CM Sepharose Fast Flow阳离子交换色谱和Sephadex G-50凝胶过滤色谱两步法分离纯化神经毒素。采用免疫组织化学技术观察神经毒素在大鼠直肠组织中的分布。利用Shotgun质谱技术和数据库检测大鼠血浆神经毒素片段。利用HE染色观察神经毒素对大鼠直肠组织结构的影响。利用醋酸扭体法测定神经毒素直肠给药后镇痛活性。结果 通过色谱分离纯化得到电泳纯的神经毒素。神经毒素直肠给药3 h后直肠黏膜组织内神经毒素分布明显,阳性面积比率、平均光密度值、H-SCORE值与对照组相比差异明显(P<0.01)。质谱检测到大鼠血浆中神经毒素有关片段。HE染色表明神经毒素对大鼠直肠组织没有损伤,组织结构无明显病理变化。醋酸扭体法测定小鼠直肠给药神经毒素3 h后扭体抑制率达50%,提示具有镇痛活性。结论 眼镜蛇神经毒素可以通过直肠吸收入血并且发挥镇痛作用,为后续研究眼镜蛇神经毒素直肠给药制剂提供实验依据。     

灯盏花素对糖尿病大鼠肝脏保护作用的实验研究

目的　探讨灯盏花素对糖尿病大鼠肝脏保护作用。方法　建立STZ诱导的糖尿病模型 ,随机分 4组 :对照组、模型组、灯盏花素给药组、维生素E给药组 ,每组 10只 ,观察8wk。应用分光光度法检测肝组织MDA含量及SOD、CAT与GSH PX活性 ;HE染色对肝组织作病理检查 ;油红O染色观察肝组织脂肪浸润 ;肝组织ED1(单核 巨噬细胞表面标志 )免疫组织化学采用SABC技术。结果　灯盏花素给药组对糖尿病大鼠血糖、体重无明显影响 ,维生素E给药组可降低血糖 ,延缓体重下降。HE染色模型组部分肝细胞脂肪变性 ;各给药组对肝细胞保护效果较好。模型组肝细胞油红O染色评分为 2 11± 0 82 ,对照组为 0 35± 0 15 ,相比差异有显著性 (P <0 0 1) ;灯盏花素给药组评分为 0 75± 0 6 6 ,维生素E给药组评分为 1 13± 0 78,与模型组相比差异均有显著性 (P均 <0 0 1)。模型组肝组织MDA含量明显升高 ,SOD、CAT、GSH PX活性明显降低 ,各给药组均可降低肝组织MDA含量 ,提高SOD、CAT与GSH PX活性。免疫组织化学显示各给药组均能抑制糖尿病肝组织单核 巨噬细胞浸润的增加。结论　灯盏花素对糖尿病大鼠肝脏保护作用机制部分与抑制肝内脂肪浸润、氧化应激及巨噬细胞浸润有关。     

醋酸棉酚对雄性木鼠睾酮、黄体生成素(LH)和卵泡刺激素(FSH)的影响

给大鼠口服醋酸棉酚30mg/kg/d每周6次,给药2,4或8周,用放射免疫法测血清睾酮、LH和FSH水平。结果表明,给药2周(生精上皮破坏不明显)和6,8周(曲精细管严重破坏)血清睾酮水平显著下降,而血清LH无变化。给药8周时血清FSH显著升高,为对照组的4倍。实验结果提示棉酚可能影响间质细胞的功能。     

醋酸棉酚对大鼠输卵管平滑肌收缩活动的影响

观察了醋酸棉酚水溶性制剂对离体大鼠输卵管平滑肌收缩活动的影响并对其作用机制作了初步探讨。结果表明,醋酸棉酚可提高大鼠输卵管平滑肌收缩张力,但并非为激动α兴奋性肾上腺素能受体,而与促输卵管组织前列腺素(PGs)的生物合成、释放并与促Ca²⁺内流机制有关。棉酚的这种药理作用还与性周期有密切关系,对动情期输卵管的作用明显高于间情期。结果还表明,前列腺索E₁(PGE₁)和前列腺素E₂(PGE₂)均可提高大鼠输卵管平滑肌收缩活性,以PGE₁的作用较强且较持久,此作用可为醋酸棉酚所明显增强。     

川芎嗪联合丹皮酚对CCl_4致大鼠肝纤维化的抑制作用及其机制研究

目的探索川芎嗪联合丹皮酚对CCl_4致大鼠肝纤维化的抑制作用及其机制,为临床肝纤维化提供新的治疗策略。方法清洁级♂SD大鼠,随机分为空白对照组、模型组(CCl_4)、川芎嗪组、丹皮酚组以及联合用药组(川芎嗪+丹皮酚)。HE染色观察病理组织学改变,Masson染色及天狼星红染色观察胶原沉积情况,全自动生化仪检测血清中ALT、AST、ALP和羟脯氨酸,Western blot检测肝纤维化标志物。HSC-T6细胞分为模型组、川芎嗪组、丹皮酚组以及联合用药组,Western blot与Real time-PCR检测炎症及凋亡蛋白与基因的表达情况。结果川芎嗪与丹皮酚联合应用能明显改善CCl_4所致肝组织病理改变,降低血清ALT、AST、ALP及羟脯氨酸水平,抑制肝纤维化标志蛋白表达,进而减少胶原纤维的沉积,效果明显优于单独干预组。联合用药组能抑制HSC中炎症通路相关蛋白表达,促进HSC的凋亡。结论川芎嗪与丹皮酚联合应用具有明显的抗肝纤维化效应,且效果优于两者单独干预,这种效果可能是由于干扰了HSC中TNF-α/NF-κB通路,进而促进细胞凋亡,抑制了细胞外基质的生成。     

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.     

蒿甲醚对小鼠体内日本血吸虫磷酸化酶,乳酸脱氢酶,三磷酸腺苷 …

目的：观察蒿甲醚（Ａｒｔ）对日本血吸早磷酸化酶（ＰＰ）、乳酶脱氢酶（ＬＤＨ）、６－磷酸工唿科（Ｇ－６－ＰＤＨ）和三磷酸腺苷酶（ＡＴＰａｓｅ）的影响。方法：感染３２－３８天的小鼠于灌服Ａｒｔ１００－３００ｍｇ．ｋｇ＾－１后２４－７２ｈ剖 杀，收集雌（♀）、雄虫（０１６５）、按ＮＡＤＨ和ＮＡＤＰＨ的形成和无机磷的释放量测定 上述４种酶。结果：感染小鼠用Ａｒｔ３００ｍｇ．ｋｇ＾－１治疗后２４－４８ｈ，♀     

Histopathological and biochemical changes in the liver and testes of desert gerbil, after repeated exposures of Thimet (phorate)

Intraperitoneal administration of Thimet (0.6 mg/kg) on alternate days for a period of 30 days produced various pathological and biochemical changes in the liver and testes of male gerbils. Histology of the liver showed necrosis, enlarged hepatocytes and fatty degeneration. Histological changes seen in the testes were enlarged interstitium, pyknotic spermatogenic cells, reduction in tubular size and atrophy of Leydig cells. The activities of alkaline and acid phosphatases increased in both liver and testes while that of ATPase decreased significantly. The activity of G-6-Pase decreased in liver but increased significantly in testes. Partial recovery was seen 15 days after termination of Thimet treatment. The activities of acid phosphatase, ATPase of liver and alkaline phosphatase, acid phosphatase, and ATPase of testes did not return to their normal values up to 15 days after stopping the injections.     

川西獐牙菜对低张性低氧肝损伤的保护作用

高原药用植物——川西獐牙菜(Swertia mussotii Franch)注射剂及其有效成份芒果甙和总(口山)酮对模拟高原急性低氧肝损伤具有保护作用。大鼠于低压舱内模拟海拔8,000m 2小时造成急性低氧肝损伤。预先给大鼠腹腔注射川西獐牙菜注射剂6.5ml/kg,可以明显降低大鼠SGOT和肝溶酶体酸性磷酸酶的活力,同时降低肝总脂的含量。大鼠肝溶酶体体外温孵实验显示,川西獐牙菜注射剂,芒果甙和总(口山)酮有稳定溶酶体膜的作用,并直接对溶酶体酸性磷酸酶活力有抑制作用。     

Biological activities of the crude skin toxin of the Suez Gulf oriental catfish (Plotosus lineatus) and its antitumor effect in vivo (mice)

Quantitative determination of newly reported enzymes activity in the crude skin toxin (CST) of catfish revealed highest activities of hyaluronidase and lipase, lesser activities of phospholipase A2, lactate dehydrogenase (LDH), cholinesterase (CE), alkaline phosphatase (ALP), and aspartate transaminase (AST), and least activities of proteinase and 5-nucleotidase (5'-NT). The CST has a hemolytic activity of 54% and no ichthyotoxicity up to 500 ug/ml. The chosen dose of CST (LD12.5) showed a potential cytotoxic activity against solid Ehrlich carcinoma-bearing mice demonstrated by an increase in the mean survival time (238.8%) and tumor growth inhibition ratio (T/C) of 73%. The CST ameliorated the relative weights of heart and liver after three weeks, while modulating the elevation in the relative spleen weight throughout the treatment periods (three, six, and nine weeks). The levels of serum triglyceride, total cholesterol, and liver total lipids were normalized after three weeks, whereas the serum albumin and hepatic glycogen concentrations, as well as ALT, AST, 5'-NT, and G-6-Pase activities were ameliorated after 6 weeks. Serum levels of glucose, LDH, and creatine kinase (CK) activities were significantly modulated throughout the treatment periods. Histological examinations of the tumor and liver tissues of treated tumor-bearing animals were carried out. Tumor tissues showed many cytolytic and cytopathic changes after treatment, while liver tissues showed moderate dysplastic changes after six weeks of treatment, which became more marked after nine weeks.     

Long-term trophic action of alpha-melanocyte-stimulating hormone on the zona glomerulosa of dexamethasone -or captopril-treated rats, with or without maintenance doses of ACTH or angiotensin. II: Stereology and plasma hormone concentrations

The effects of a long-term (7 days) administration of alpha-melanocyte-stimulating hormone (alpha-MSH) on the zona glomerulosa were investigated in "normal" rats and in animals in which the hypothalamic-hypophyseal-adrenal axis and the renin-angiotensin system had been pharmacologically interrupted. alpha-MSH caused a notable hypertrophy of the zona glomerulosa and its parenchymal cells, as well as a significant increase in the plasma concentration of aldosterone, in rats infused with dexamethasone, dexamethasone plus ACTH or captopril plus angiotensin II, but not in animals treated with captopril alone. These findings indicate that alpha-MSH is directly involved in the stimulation of the growth and steroidogenic capacity of rat zona glomerulosa, and that this action of alpha-MSH requires a normal level of circulating angiotensin II.     

Organ- and species-specific properties of glucose-6-phosphate dehydrogenase and the effect of molsidomine

Glucose-6-phosphate dehydrogenase (G-6-PDH) is the key enzyme of the pentose phosphate cycle and therefore regulates the synthesis of the nucleic acid constituent ribose-5-phosphate. At the same time the enzyme is coupled to the synthesis of reduced glutathione (GSH) which detoxifies electrophilic molecules (radicals) in the organism. Activity and stability of G-6-PDH and the influence of SIN 1--the active metabolite of molsidomine (Corvaton)--dithiothreitol (DTT) and NADP on these parameters were studied in enzyme preparations from different organs of the rat (liver, ethmoturbinates, blood) and from blood of mouse, guinea pig, rabbit, dog and man. The highest activity of G-6-PDH was measured in rat ethmoturbinates (69.26 +/- 5.91 mU/mg protein/min), the lowest in human blood (2.99 +/- 0.18 mU/mg protein/min). G-6-PDH of rat ethmoturbinates and of rat and dog blood was unstable and nearly completely inhibited by SIN 1. The enzyme of rat liver and of human, mouse, guinea pig and rabbit blood was stable and not influenced by SIN 1. These organ-and species-specific findings are discussed with respect to the toxicological actions of SIN 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucose-6-phosphate dehydrogenase and gama-glutamyltranspeptidase activities in the liver during chemically induced hepatocarcinogenesis in rats and mice

Glucose-6-phosphate dehydrogenase (G-6-PDH) and γ-glutamyltranspeptidase (γ-GTP) were studied in the liver of rats and mice receiving a diet which contained 3′-methyl-4-(dimethylamino)azobenzene (3′-Me-DAB), diethylnitrosamine (DEN), or o-aminoazotoluene (o-AT). Elevated G-6-PDH activity was first observed within 2 weeks after the start of 3′-Me-DAB feeding, reaching a maximum at 4 weeks. There was a decrease from the 4-week level at about 6 weeks, followed by a sustained increase. The maintained activity after 8 weeks was about 6 times higher than in control rat liver. γ-GTP activity in rat liver increased immediately after the start of 3′-Me-DAB feeding; it was about 12 times the control value after 3–4 weeks. At 5–6 weeks, the activity decreased somewhat from the 3 to 4-week level, but this was followed by a further sustained increase. In rats receiving the DEN-containing water, the liver G-6-PDH and γ-GTP activities changed in the same way as in the 3′-Me-DAB-fed rats. Both activities increased in the early stage, reaching a maximum by 6 weeks, subsided at 7 weeks, and rose again from 9 weeks. In mice receiving o-AT-containing diet, hepatic G-6-PDH activity also changed in a biphasic pattern and closely related with that of liver γ-GTP activity.     

Anti-inflammatory activity of a new quinoid polyradical (FL-70)]

The anti-inflammatory activity of FL 70, a derivative of 2,5-dihydroxy-benzoic acid, was examined in a number of conventional experimental models. In addition, FL-70 was tested for its inhibitory action on enzymes. The results were as follows: 1. The induction of a local inflammatory reaction and the subsequent i.v. injection of trypan blue showed that FL 70 reduces the capillary permeability. 2, FL-70 significantly suppresses exudation in the formalin-induced peritonitis of the rat. 3. A slight inhibition of an edema in the footpad of the rat induced by formalin-dextran was not shown to be statistically significant. 4. Local swelling could be markedly inhibited in the turpentine-oil induced inflammatory reaction of the rabbit. 5. Exudation and formation of granulomatous tissue was inhibited in Selye's granuloma. 6. FL-70 markedly inhibited the local inflammatory reaction accompanying the cutaneous reaction in experimental vaccinia infection of the rabbit skin. The size of the infiltration after intracutaneous infection of the virus was not reduced. 7. FL-70 could not prevent the onset of clinical signs, if administered in experimental allergic encephalitis. 8. The activity of acid phosphatase was inhibited by FL-70. Alcaline phosphatase, cholinesterase, leucin aminopeptidase, glucose-6- phosphatase-dehydrogenase (G-6-PDH), trypsin and chymotrypsin were unaffe-ted. FL-70 inhibits the following, G-6-PDH activated reduction process: glucose-6-phosphate (see article).