昆布多糖药理作用的研究进展

昆布中富含多种功能性物质。其中具有重要生物活性的物质主要为多糖，主要包括褐藻胶、褐藻糖胶、褐藻淀粉3种。在调节免疫、抗肿瘤、抗凝血、调血脂、降血糖、抗辐射、抗氧化等方面具有独特的功能。     

海带多糖对实验性高脂血症鹌鹑血流变及微循环的影响

目的:研究海带多糖对实验性高脂血症鹌鹑血流变及微循环的影响。方法:采用高脂饲料诱导鹌鹑建立高脂血症模型,注射海带多糖(2,4,8 mg·kg-1,qd)2周后,测定血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)浓度,计算HDL／TC值;测定全血低切(LS)、全血中切(MS)、全血高切(HS)、纤维蛋白原(Fg)以及红细胞压积(HT);观察肠系膜毛细血管交点数、微动脉管径、血流速度。结果:海带多糖显著降低血清TC,TG和LDL浓度,显著升高HDL／TC比值;明显改善血流变及微循环各项指标,并具有剂量依赖性。结论:海带多糖具有降血脂,改善血流变,改善微循环的药理活性。     

Effects of beta-cypermethrin on male rat reproductive system

To study adverse effects and underlying mechanisms of beta-cypermethrin (β-cyp) on male reproductive system, the 15-day intact male adult Sprague-Dawley (SD) rats assay was used as an in vivo test. Male adult SD rats were treated by oral gavage with 0, 15 and 30mgβ-cyp/kgBW for 15 days. After 15-day treatments, the testes, epididymis and seminal vesicles were excised and weighed, respectively. One testis was used for testicular sperm head counts, and the other was for immunohistochemistry test to characterize the expression of androgen receptors (ARs). There were substantial decreases of both sperm head counts and daily sperm production after β-cyp exposure. The expression of AR decreased significantly in rats treated with 15 and 30mgβ-cyp/kgBW, and the gray scale pixel values in the three groups (0, 15 and 30mgβ-cyp/kgBW) were 113.79±13.58, 96.09±5.95 and 77.27±5.44, respectively. These findings suggested β-cyp has significant adverse effects on the reproductive system. Reducing the expression of AR is a potential mechanism of decreased sperm production caused by β-cyp.     

Effects of beta-cypermethrin on male rat reproductive system

To study adverse effects and underlying mechanisms of beta-cypermethrin (β-cyp) on male reproductive system, the 15-day intact male adult Sprague–Dawley (SD) rats assay was used as an in vivo test. Male adult SD rats were treated by oral gavage with 0, 15 and 30 mg β-cyp/kg BW for 15 days. After 15-day treatments, the testes, epididymis and seminal vesicles were excised and weighed, respectively. One testis was used for testicular sperm head counts, and the other was for immunohistochemistry test to characterize the expression of androgen receptors (ARs). There were substantial decreases of both sperm head counts and daily sperm production after β-cyp exposure. The expression of AR decreased significantly in rats treated with 15 and 30 mg β-cyp/kg BW, and the gray scale pixel values in the three groups (0, 15 and 30 mg β-cyp/kg BW) were 113.79 ± 13.58, 96.09 ± 5.95 and 77.27 ± 5.44, respectively. These findings suggested β-cyp has significant adverse effects on the reproductive system. Reducing the expression of AR is a potential mechanism of decreased sperm production caused by β-cyp.     

海带在四氧嘧啶糖尿病大鼠模型中的降糖作用

目的探讨海带在四氧嘧啶糖尿病模型大鼠中的降血糖作用及其机制。方法健康♂Wistar大鼠60只,随机取10只作为对照组,其余50只腹腔注射四氧嘧啶建立高血糖动物模型,饲料中添加含有海带的饲料喂养干预治疗,分为低(2.5 g.kg-1)、中(10 g.kg-1)和高(25 g.kg-1)3个剂量组。自动血糖仪测大鼠空腹血糖(FBG),酶联免疫吸附法检测血清胰岛素(Insulin)水平,硫代巴比妥酸法检测血清脂质过氧化物丙二醛(MDA)含量,硝酸还原酶法检测血清一氧化氮(NO)含量,黄嘌呤氧化酶法测定血清超氧化物歧化酶(SOD)活性,化学比色法测定谷胱甘肽过氧化物酶(GSH-Px)活性。结果经海带治疗后,动物血清胰岛素水平较模型组升高(P<0.05),中、高剂量组动物FBG水平较模型组降低(P<0.05);其血清MDA和NO水平低于模型组,而血清SOD和GSH-Px活性高于模型组,其中中、高剂量组与模型组比较差异有显著性(P<0.05)。各指标在中剂量与高剂量组之间差异无显著性(P>0.05)。结论海带可通过增强机体的抗氧化作用,促进胰岛细胞分泌功能恢复而发挥降血糖作用,其理想剂量为每日10 g.kg-1。     

The effects of carbon disulfide on the reproductive system of the male rat

Two experimental protocols were employed to determine the effects of carbon disulfide (CS₂) on the reproductive system of the male rat. In the first experiment, adult Long Evans hooded rats were exposed to 0,350 or 600 ppm CS₂ vapor for 10 weeks (5 h/day, 5 days/week). CS₂ exposure caused no change in reproductive organ weights nor in plasma gonadotropin levels. However, animals exposed to 600 ppm CS₂ had slightly lower epididymal sperm counts and significantly reduced plasma testosterone levels. In order to determine if monitoring hormone levels and sperm status in the same male over time might increase the sensitivity of detecting a toxic reaction, the second protocol was employed. Male rats were exposed to 0 or 600 ppm CS₂. After 0, 1, 4, 7 and 10 weeks of exposure, males were observed for mating behavior, and ejaculated sperm count and plasma hormone levels were determined. Animals exposed to 600 ppm CS₂ had significantly shorter times to mount and to ejaculate and decreased ejaculated sperm counts. Plasma gonadotropin levels were similar in both groups while plasma testosterone levels were marginally depressed in CS₂-exposed animals in the early weeks. These data indicate that CS₂ is a toxin of the male reproductive system resulting in abnormal coital behavior and decreased sperm counts. The second experimental protocol proves to be a sensitive method for assessing adverse effects in the male reproductive system.     

Influence of hemicellulose based anticoagulant on male rat reproductive function

Results of estimation of the effect of a new hemicellulose-based anticoagulant drug on the reproductive function of white male rats are presented. No negative impact on the fertility and breed was observed for the drug administered in doses of 5 and 25 mg/kg. However, in a dose of 50 mg/kg, the new drug negatively affected spermatogenesis and decrease the reproductive function of male rats.     

The effect of oral contraceptives on reproductive function during semichronic exposure to ethanol by the female rat

• 1.1. Female rats were placed on water, 5% ethanol (ET), or 20% ET drinking solutions for 8 weeks. The last 2 weeks, the rats received orally either ethinyl estradiol (EE), norethindrone acetete (NED), or a combination of both.
• 2.2. Luteinizing hormone decreased due to ET drinking and was undetectable subsequent to the steroidal treatment.
• 3.3. Prolactin increased after steroid treatment and alcohol drinking in the controls.
• 4.4. Ethanol (5%) plus EE increased prolactin as did the steroidal combination, whereas ET (20%) likewise increased prolactin in conjunction with NED over water controls.
• 5.5. Hepatic alcohol dehydrogenase was inhibited due to EE when compared to water-controls in the 5% ET drinking animal, whereas aldehyde dehydrogenase was induced in combination with NED in both the 5% and 20% ET drinking rats.

     

Effects of cannabinoids given orally and reduced appetite on the male rat reproductive system

Chronic oral treatment of young adult male Fischer rats with delta 9-tetrahydrocannabinol (THC), 1, 5 and 25 mg/kg/day, or crude marihuana extract (CME), 3, 15 and 75 mg/kg/day, suppresses growth of accessory sex organs and body weight gain in a dose-related manner. Animals pair fed with the THC (25 mg/kg) group gained slightly more in body weight than the THC group, but their relative accessory sex organ weights were intermediate between THC and ad libitum-fed control group weights. These latter differences may be due to altered serum androgen levels since these levels 2-6 h after last treatment were 0.15, 0.77 and 3.33 ng/ml for THC, pair-fed and ad libitum-fed groups, respectively. 24 h after the last treatment all groups were within normal levels. Thus, chronic cannabinoid treatment suppresses accessory sex organ weights and serum androgen levels greater than the suppression caused by reduced food intake alone.     

Effects of maternal exposure to diethylstilbestrol on the development of the reproductive system and thyroid function in male and female rat offspring

Diethylstilbestrol (DES) was administered subcutaneously at 1.5 or 15 microg/kg/day (DES 1.5 group, DES 15 group) to pregnant SD rats daily on days 7-21 of gestation to investigate its effects on the development and functions of the reproductive system and thyroid gland in their offspring. Of the 11 pregnant rats in the DES 15 group, only one delivered a live pup. Rat pups in the DES 1.5 group were autopsied at 1, 3, or 6 weeks after birth. In the DES 1.5 group, the plasma T4 concentrations at all weeks of age at autopsy were significantly increased, the TSH concentration at 6 weeks of age was also significantly increased, and the height of thyroid follicular epithelial cells was increased at 3 weeks. The testosterone concentration in the DES 1.5 group at 6 weeks was significantly decreased and the plasma LH concentration was increased. The DES treatment increased the plasma FSH concentration in female pups at 3 weeks, increased the percentages of primary and secondary ovarian follicles, and decreased the percentage of primordial follicles, but did not influence the timing of the vaginal opening or the onset of the estrous cycle. These observations indicate that prenatally administered DES increases thyroid function, and has an inhibitory effect on testicular function and a promoting effect on female reproductive function.     

The effect of sodium valproate on the biochemical parameters of reproductive function in male albino Wistar rats

Objective:

To assess the effects of sodium valproate on intratesticular testosterone and lactic dehydrogenase level in rats.

Methods:

Male Wistar rats (12 weeks old) were treated with sodium valproate and sacrificed at the end of the 2^nd, 4^th, 5^th, 7^th, 10^th and 15^th week, after the last exposure to sodium valproate. The testes were removed, weighed and processed for biochemical analysis.

Results:

The intratesticular testosterone level was significantly (P<0.001) reduced in 200 mg/kg and 400 mg/kg treated rats. The intratesticular lactate dehydrogenase (LDH) level was significantly (P<0.001) increased by valproate in a time dependent manner.

Conclusion:

Valproate causes reversible change in intratesticular testosterone and LDH level.     

The effects of methyl tert-butyl ether (MTBE) on the male rat reproductive system

Methyl tert-butyl ether (MTBE) is an oxygenated compound, which has been widely used in Asia, Europe and North America. Although numerous in vitro and in vivo studies have demonstrated the carcinogenicity and the toxicity of MTBE, there is still a lack of data on reproductive system exposure of MTBE in male rodent animals. We studied subacute exposure of MTBE on the reproductive systems of male Sprague-Dawley rats. MTBE was administered to rats at dose levels of 0, 400, 800 and 1600 mg/kg/day. After 2 or 4 weeks of treatments, the rats were euthanized, and their serum, epididymis and testes were collected. Significant adverse effects in their reproductive system were observed including: a significant increase in the percentage of abnormal sperm; an irregular and disordered arrangement of the seminiferous epithelium indicated by a histopathological examination; changed serum levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH); and decreased levels of mRNA and of androgen binding protein (ABP). In the oxidative stress study, results indicated an increased maleic dialdehyde (MDA) content, implying a raised peroxide level, and that the total antioxidant ability in serum was significantly increased. This finding was especially strong at 1600 mg/kg/day MTBE. In the 2-week treatment, at 1600 mg/kg/day, the mRNA level of 8-oxoguanine DNA glycosidase (OGG1) was significantly decreased, and the mRNA level of the extra-cellular form of superoxide dismutase (SOD(EX)) was significantly increased. Our experiments suggest that relatively high doses of MTBE can exert reproductive system toxicity of male rats and disturb the secretions of T, LH and FSH, possibly due to oxidative stress induced by MTBE.     

Effect of acute exposure to boric acid on the male reproductive system of the rat

Adult male rats were dosed orally on d 0 with 0 or 2000 mg/kg of boric acid and killed on posttreatment d 2, 14, 28, and 57, or dosed with 0, 250, 500, 1000, or 2000 mg/kg of boric acid and killed on posttreatment d 14. At d 14, atypical structures that appeared to be enlarged irregular cytoplasmic lobes of Step 19 spermatids were observed in Stage VIII seminiferous tubules of rats dosed with 1000 and 2000 mg/kg. Abnormal retention of Step 19 spermatids and residual bodies was also observed in Stage IX-XIII tubules of these rats. The retained spermatids and residual bodies were seen in both the luminal and basal regions of the epithelium. A substantial increase in the testicular sperm head count occurred in animals dosed with 2000 mg/kg. Abnormal caput epididymal sperm morphology and reduced caput epididymal sperm reserves were observed at 1000 mg/kg and higher. Serum LH, FSH, TSH, and prolactin values were not affected at any dosage. At d 28, rats dosed with 2000 mg/kg exhibited continued retention of Step 19 spermatids into Stage X, abnormal caput and cauda sperm morphology, and decreased percentages of motile cauda spermatozoa with reduced straight-line swimming velocities. By d 57 substantial recovery was apparent; some retention of Step 19 spermatids into Stage X tubules was still present in two out of six rats but the sperm parameters were comparable to controls. The study indicated that acute oral exposure to boric acid adversely affected spermiation and sperm quality in the adult male rat. At the dosages used the effects appeared reversible. The no-effect level was 500 mg/kg.     

氟他胺对仔鼠雄性生殖系统的影响

目的探讨宫内暴露氟他胺对雄性仔鼠生殖系统的影响。方法孕鼠随机分为5个实验组及一个对照组,从孕12~17d连续6d实验组每天腹部皮下注射用生理盐水配制的氟他胺4492.2、4882.8、5273.4、5664.0、6054.6μg/kg,对照组注射同量生理盐水;于怀孕20d行剖宫术,提取雄性仔鼠睾丸,做电镜检测;并于出生后第2、13、28d观察雄性仔鼠性分化与性发育的指标。结果染毒组雄性子代肛殖距除4492.2μg/kg剂量外,其余各组均明显小于对照组(P<0.01);尿道下裂的发生率依次为0、29.00%、63.68%、93.02%、100%;单侧隐睾发生率分别为0、4.55%、8.70%、13.95%、15.56%;乳晕延迟退化率均为100%;各组前列腺不发育或发育不全。电镜检测的结果表明睾酮生成的细胞器受损。结论宫内暴露于氟他胺可使雄性仔鼠性分化与性发育异常。     

The effect of disodium 5-ribonucleotide on reproductive function over three generations in the rat.

Deitary levels of 0.1, 1.0 and 2.0% disodium 5-ribonucleotide were administered to rats of the CD strain over 3 generations, and the growth and reproductive performance were compared with those of a control group. Treatment did not appear to affect parent animals, as assessed by the incidence of mortality, bodyweight change, food consumption, mating performance, Pregnancy rate, Gestation Peroid, and post-mortem findings. Total litter loss, Litter size, Litter and mean pup weights, pup mortality and the incidence of skeletal or other variants in the offspring were unaffected by treatment at any dosage level. Additional organ weight analysis and skeletal staining of 10 males and 10 females from all groups, and the histological examination of 10 male and 10 females of the control and 2.0% level groups of the third generation did not provide any evidence of effects that could be related to treatment.     

The toxic effects of nonylphenol on the reproductive system of male rats

Male Sprague-Dawley (SD) rats were exposed to 4-t-nonylphenol (NP) by gavage at dosages of 0, 125 and 250 mg/kg/day for 50 days. Organ weights of liver, kidney, testis and epididymis were measured. Sperm number in the head of epididymis was counted. Several hormones including testosterone, luteinizing hormone and follicle stimulating hormone were measured. Testicular sections were observed by light and electron microscopy. Terminal dideoxynucleotidyl transferase dUTP nick end labeling assay was performed to probe the apoptotic cells in seminiferous tubules. When rats were treated with nonylphenol at 250 mg/kg/day, the absolute and relative weight of epididymis decreased dramatically, while the relative weights of kidney and liver increased by 14 and 22%, respectively. In addition, the sperm density of the head of epididymis and the testosterone level descended at 250 mg/kg/day. The levels of luteinizing hormone and follicle stimulating hormone increased in both nonylphenol treated groups. Pathological changes were detected by microscopy and the transferase dUTP nick end labeling (TUNEL) assay showed that the number of apoptotic cells in testes increased with nonylphenol in a dose-dependent manner.     

The effect of nibufin on reproductive function and the contraceptive effect of hormonal preparations

215 pubescent female rats were administered with nibufine in 3 series; over a 10-day period with a daily dose of .8 mg/kg, over a 14-day period with a daily dose of .8 mg/kg together with 1.5 mg/kg of megestranol, and with a dose of .8 mg/kg together with cholinesterase, amizile (10 mg/kg), or spazmolitine (30 mg/kg). Nibufine inhibited the activity of cholinesterase in the blood, disturbed the reproductive function, and strengthened the depressive effects on reproduction of the synthetic oral contraceptives megestranol and particularly infecundin. The ill effects of nibufine of the reproductive function were significantly reduced under the influence of amizile. The effects of spazmolitine was less pronounced.     

Effect of propetamphos on the male rats reproductive system

The present study aimed at defining the testicular toxicity of propetamphos. Mature male albino rats (5-6 months old) were treated with propetamphos orally at doses of 0, 0.18, 0.38, 0.75, 1.5 and 3mg/kg/day for 60 consecutive days. Propetamphos at a dose of 0.38 mg/kg/day significantly reduced the sperm motility only. At 0.75 mg/kg/day sperm count, sperm motility, plasma testosterone level and activity of sorbiol dehydrogenase (SDH) were significantly reduced and sperm morphological abnormalities were significantly increased. At 1.5mg/kg/day weight of testes, seminal vesicle and epididymis were reduced dose dependently whereas, at 3mg/kg/day, weight of prostate gland and activities of acid phosphatase (ACP) and glucose-6-P-dehydrogenase (G6PDH) were decreased significantly. On histopathological examination indicated toxicity of propetamphos on testes depending on dose and observed at doses higher than 0.38 mg/kg/day. These results indicate testicular toxicity of propetamphos at dose of 0.38 mg/kg/day or higher in male albino rats.     

Effects of propyl paraben on the male reproductive system

Parabens are p-hydroxybenzoic acid ester compounds widely used as preservatives in foods, cosmetics, toiletries and pharmaceuticals. These compounds exert a weak estrogenic activity as determined by in vitro estrogen receptor assay and in vivo uterotrophic assay. In a previous study, it was demonstrated by the present author that exposure of post-weaning mammals to butyl paraben adversely affects the secretion of testosterone and the function of the male reproductive system. In the present study, it is shown that propyl paraben also adversely affects the hormonal secretion and the male reproductive functions. Propyl paraben was administered to 3-week-old rats which were divided into four groups of eight animals each, at doses of 0.00, 0.01, 0.10 and 1.00% with the AIN93G modified diet. At the end of 4 weeks, the rats were sacrificed by decapitation and the weights of testes, epididymides, prostates, seminal vesicles and preputial glands were determined. There were no treatment-related effects of propyl paraben on the organ weights in any of the study groups. The cauda epididymal sperm reserves and concentrations decreased in a dose-dependent manner and the difference was significant at dose of 0.10% and above. Daily sperm production and its efficiency in the testis of all groups receiving propyl paraben significantly decreased. The serum testosterone concentration decreased in a dose-dependent manner and the decrease was significant in the group that received the highest dose. The exposure level at which this effect was observed is the same as the upper-limit acceptable daily intake (10 mg/kg body weight/day) of parabens in the European Community and Japan.