对苯二甲酸亚慢性肾毒效应的动态观察

为研究对苯二甲酸（ＴＰＡ）亚慢性毒性并为制定其卫生标准提供依据,以５０００、５００、５０ｍｇ／ｋｇ３个剂量ＴＰＡ对ＳＤ大鼠连续染毒９０天,动态观察大鼠血清酶（ＡＳＴ、ＧＰＴ、ＡＬＢ、ＡＬＰ、ＮＡＧ、ＧＧＴ）和尿酶（ＡＳＴ、ＡＬＰ、ＮＡＧ、ＧＧＴ、α１－ＭＧ）等参数的变化。结果表明：３０天时,５０００ｍｇ／ｋｇ剂量组尿α１－ＭＧ、ＮＡＧ有一过性升高（Ｐ〈０．０５）,５００、５０ｍｇ／ｋｇ剂量组ＡＬＰ     

谷胱甘肽及VitB6对CS2染毒大鼠的保护作用研究

目的：为探讨金属离子络合及ＶｉｔＢ６代谢障碍在二硫化碳（ＣＳ２）神经毒作用中的作用；方法：测定ＣＳ２染毒大鼠脑组织中微量元素铜的含量，并用ＶｉｔＢ６及谷胱甘肽（ＧＳＨ）进行干预。以ＳＤ雄性大鼠为中毒模型，检测不同浓度（０，３００，６００，１２００，２４００ｍｇ／ｍ３）染毒两个月后脑组织铜的含量；同时在高浓度（２４００ｍｇ／ｍ３）组给予两种干预药物：ＧＳＨ（１００ｍｇ／ｋｇ，腹腔注射，一次／日），ＶｉｔＢ６（灌胃，一次／日，０．４ｍｇ／日），观察对大鼠行为及酶活性的影响。结果：ＣＳ２染毒大鼠脑组织铜含量无明显改变；ＧＳＨ，ＶｉｔＢ６对ＣＳ２致运动协调能力障碍无明显改善，对反映学习记忆能力的指标（步下法）有改善作用；ＧＳＨ对Ｎａ＋－Ｋ＋－ＡＴＰ酶活性有升高作用。结论：ＣＳ２所致中枢神经系统与外周神经系统毒性在机制上可能有所不同。     

甘草甜素和齐墩果酸对大鼠镉中毒性肝损伤的防护作用与机理

为探讨甘草甜素（ＧＬ）和齐墩果酸（ＯＡ）对大鼠镉中毒性肝损伤的防护作用及其作用机理,给大鼠腹腔注射ＣｄＣｌ２溶液（０．８ｍｇＣｄ＾２＋／ｋｇ体重）,两组染镉大鼠分别同时皮下注射ＧＬ的生理盐水溶液（２０ｍｇ／ｋｇ,每周３次）和ＯＡ的吐温－生理盐水混悬液（６０ｍｇ／ｋｇ,每周５次）,测定血清转氨酶、肝镉（Ｃｄ）、金属硫蛋白（ＭＴ）含量,检查肝组织病理形态学。结果显示：ＧＬ和ＯＡ延缓、降低了镉引起的血清     

铅对大鼠不同脑区IEG表达的影响

为了研究即刻早期基因（ＩＥＧ）在铅的神经毒性机制中的作用,本实验应用ＦＯＳ和ＪＵＮ蛋白免疫组织化学方法对腹腔注射染铅１３ｍｇ／ｋｇ及１３０ｍｇ／ｋｇ的大鼠不同脑区ｃ－ｆｏｓ、ｃ－ｊｕｎ表达水平进行了观察。图像分析及统计检验结果表明,急性染铅２小时后,大鼠脑组织皮层、海马ＣＡ３区及小脑的ｃ－ｆｏｓ、ｃ－ｊｕｎ表达的阳性面积比［Ａａ（％）］、平均灰度或阳性细胞个数等参数与对照组相比有显著性差异（Ｐ＜０．０５）,即染铅组ＩＥＧ表达高于对照组。这一结果提示第三信使ＩＥＧ作为转录调控因子可能参与了铅对学习记忆损害的神经毒性过程。这对深入阐明铅神经毒性的分子机制提供了一定的实验依据。     

EGE与甲苯和二甲苯联合处理对大鼠EGE代谢和睾丸的影响

男油漆工接触乙二醇乙醚（ＥＧＥ）可引起睾丸萎缩。本研究观察了ＥＧＥ与甲苯和二甲苯联合处理对大鼠睾丸萎缩和血浆中乙氧基乙酸（ＥＡＡ）生成的影响。选用雄性大鼠,体重２５０～３００ｇ。为观察不同剂量ＥＧＥ单独以及与甲苯和二甲苯联合处理对大鼠睾丸的影响,每日经口单独给大鼠ＥＧＥ橄榄油溶液５０、１００、２００、５００和１０００ｍｇ／ｋｇ;同时与甲苯２５０ｍｇ／ｋｇ、二甲苯５００ｍｇ／ｋｇ及甲苯５００ｍｇ／ｋｇ和二甲苯１０００ｍｇ／ｋｇ共同处理;对照组经口给橄榄油０８ｍｌ,每周６次共４周,在最后一次染毒后…     

镓砷和氧化镓肺毒性的比较

作者已报道过ＧａＡｓ对肺与精巢的毒性。本文比较镓的影响,给仑鼠及大鼠气管内反复给与ＧａＡｓ粒子和氧化镓（Ｇａ２Ｏ３）粒子,比较研究通过呼吸道接触各物质的肺毒性。方法：使用８周龄的雄性仑鼠和２周龄的Ｗｉｓｔａｒ雄性大鼠。将其分为ＧａＡｓ组、Ｇａ２Ｏ３组与对照组,仑鼠各组１２只（对照组１１只）,大鼠各组８只。每次投与ＧａＡｓ８．０ｍｇ／ｋｇ（３．９ｍｇＧａ／ｋｇ）,Ｇａ２Ｏ３５．２ｍｇ／ｋｇ,（３．９ｍｇＧａ／ｋｇ）,均悬浮于磷酸缓冲液。向仑鼠及大鼠气管内每周投药２次,计１６次。对照组仅投与磷酸缓冲…     

载硒酵母对小鼠化学性肝损伤的影响

观察不同剂量（３０，６０，９０ｍｇ／ｋｇ）载硒酵母（ｓｅｌｍｉｎｍ－ｅｎｒｉｃｈｅｄｙｅａｓｔ，ＳＥＹ）ｉｇ７天对ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ引起的化学性肝损伤的保护作用。结果发现：ＳＥＹ６０ｍｇ／ｋｇ可降低ＣＣｌ４所致血清ＡＬＴ的升高，各剂量组均可降低Ｄ－Ｇａｌ－Ｎ所致血清ＡＬＴ和ＡＳＴ的升高，ＳＥＹ３０ｍｇ／ｋｇ可减轻Ｄ－Ｇａｌ－Ｎ所致肝病理损伤，各剂量组ＳＥＹ均可降低Ｄ－Ｇａｌ－Ｎ所致肝匀浆ＭＤＡ含量升高。提示ＳＥＹ在一定程度上可减轻ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ的化学性损伤，其作用机制可能与抗氧化作用有关。     

杀鼠迷的毒性和致突变性研究

杀鼠迷的ＬＤ５０值分别为：大鼠３．１６ｍｇ／ｋｇ（经口）和２．７０ｍｇ／ｋｇ（经皮）；小鼠２６９ｍｇ／ｋｇ（经口，概率单位法）、２３７．０ｍｇ／ｋｇ（经口，霍恩氏法）和６．８１ｍｇ／ｋｇ（经皮）。蓄积系数为０．４。以上结果表明杀鼠迷为高毒性和高蓄积的化学物质，并容易通过皮肤吸收。杀鼠迷的Ａｍｅｓ试验，小鼠骨髓细胞微核试验和精子畸变试验均为阴性。     

浸螺杀的毒性和致突变性

灭螺药浸螺杀的ＬＤ５０值为小鼠１１００ｍｇ／ｋｇ（♂）和１２８２ｍｇ／ｋｇ（♀），大鼠２０４２ｍｇ／ｋｇ（♂）和１９５０ｍｇ／ｋｇ（♀），属低毒物质。蓄积毒性实验表明无明显蓄积毒性，使用浓度下对家兔的眼和皮肤无刺激性。Ａｍｅｓ试验和小鼠骨髓嗜多染红细胞微核试验均未见阳性。     

维生素E、C和B_2联用对鼠脂质过氧化、血脂及脂肪肝的影响

为了提高维生素的抗氧化作用，本研究将维生素Ｅ、Ｃ和Ｂ２联用，观察其对血脂、脂质过氧化的作用效果。结果表明：维生素Ｅ（１００ｍｇ／　ｋｇ）、维生素Ｃ（３００ｍｇ／ｋｇ）和维生素Ｂ２１０ｍｇ／ｋｇ）三者联用可明显降低四氧嘧啶诱发高脂质过氧化物血症小鼠血中ＭＤＡ、ＴＣ及ＴＧ含量，其效果优于两两维生素联用，也伏于单用维生素Ｅ组。无论是预防试验还是治疗试验，维生素Ｅ、Ｃ和Ｂ２联用都可降低食饵性高血脂大鼠模型血中ＴＣ、ＴＣ／ＨＤＬ－Ｃ比值和动脉硬化指数（Ａｌ），升高ＨＤＬ－Ｃ含量，其中以高剂量维生素补充组效果最佳。     

Effect of ethanol on ascorbate release in the nucleus accumbens and striatum of freely moving rats.

An in vivo voltammetry technique was used to monitor the extracellular ascorbate (AA) concentration in the nucleus accumbens and striatum of unanesthetized, freely moving rats. A single injection of ethanol, 1.0 g/kg intraperitoneally (IP), induced a significant increase in extracellular AA concentration in both the nucleus accumbens and striatum. This effect was dose dependent within a dose range from 0.5-2.0 g/kg. 4-Methylpyrazole (50 mg/kg, IP), which inhibits alcoholdehydrogenase, could not prevent the increase in AA concentration, evoked by ethanol. Furthermore, systemic administration of acetaldehyde (20 mg/kg, IP), the main metabolite of ethanol, did not have any effect on the level of AA in the nucleus accumbens or striatum. These results show that ethanol can alter the brain extracellular AA levels and that this effect seems to be attributed to ethanol itself and not to acetaldehyde. Consequently, these results indicate that a role for AA in the action of ethanol in the brain should be considered.     

Effects of Morphine on Metabolism of Dopamine and Serotonin in Brains of Alcohol-Preferring AA and Alcohol-Avoiding ANA Rats

Morphine induces a larger locomotor stimulation in the alcohol-preferring AA rats than in the alcohol-avoiding ANA rats. We have now studied the acute effects of morphine (1 and 3 mg/kg) on metabolism of dopamine and serotonin (5-HT) in the dorsal and ventral striatum of the AA and ANA rats. The basal level of dopamine release, as reflected by the concentration of dopamine metabolite 3-methoxytyramine (3-MT), was lower in the caudate-putamen and nucleus accumbens of the AA rats than in the ANA rats. In the caudate-putamen, morphine increased dopamine metabolism and release more in the AA than in the ANA rats. In the nucleus accumbens and olfactory tubercle, the effects of morphine on dopamine metabolism and release did not differ between the rat lines. Morphine elevated the metabolism of 5-HT in the caudate-putamen and nucleus accumbens of the AA but not in those of the ANA rats. The results suggest that the larger morphine-induced psychomotor stimulation of the AA rats in comparison with the ANA rats is associated with the larger effect of morphine on dopamine metabolism in the caudate-putamen and 5-HT metabolism in the caudate-putamen and nucleus accumbens. Furthermore, low basal dopamine release may play a role in the high alcohol-preference of AA rats.     

丙烯酰胺的毒性研究

本文AAM的急性毒性试验,昆明小鼠经口LD_(50)为154mg/kg。动物慢性中毒以后肢瘫痪、坐骨运动神经传导速度减慢和周围神经病理损伤为主,并有剂量—反应关系。AAM对皮肤粘膜有一定的刺激作用。Amse试验、染色体畸变和微核试验皆为阴性。     

Combined administration of low-dose gossypol acetic acid with desogestrel/mini-dose ethinylestradiol/testosterone undecanoate as an oral contraceptive for men

To evaluate the efficacy and feasibility of a new regimen of low-dose gossypol acetic acid (GA) combined with desogestrel/ethinylestradiol and testosterone undecanoate (DSG/E/TU) as a male contraceptive, adult male rats were fed orally with GA (12.5 mg/kg/day) and DSG (0.125 mg/kg)/E (0.025 mg/kg)/TU (100 mg/kg) daily for 8 weeks as loading dose until infertility, and a similar low dose of GA alone for infertility maintenance. Control animals were administered a single low dose of GA (12.5 mg/kg/day) or DSG (0.125 mg/kg)/E (0.025 mg/kg)/TU (100 mg/kg), and vehicle, respectively. Results demonstrated that the combined dosage regimen could damage epididymal sperm motility and density, and induce infertility within 8 weeks in rats; the infertility could be consistently sustained by giving single GA (12.5 mg/kg/day), and was reversible in about 8 weeks following withdrawal of gossypol. The regimen rendered treated male rats with spermiation failure within a period of 6-20 weeks of treatment. Also, the serum luteinizing hormone, follicle-stimulating hormone and testicular interstitial fluid testosterone levels showed a transient decrease at the end of 6 or 8 weeks, which returned to control levels after 8 weeks of recovery phase. No hypokalemia or other adverse effects in viscera were observed. These results provide a promising approach to using the new regimen for the development of an effective and reversible oral male contraceptive.     

DL- and PO-phosphatidylcholines as a promising learning and memory enhancer

In the water maze test, oral administration with 1,2-dilynoleoyl- sn -glycero-3-phosphocholine (DLPhtCho)(5 mg/kg) alone or DLPhtCho (5 mg/kg) plus 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphocholine (POPhtCho)(5 mg/kg) significantly shortened the prolonged acquisition latency for rats intraperitoneally injected with scopolamine, with more efficient effect than (POPhtCho)(5 mg/kg) alone, arachidonic acid (AA)(5 mg/kg) alone, docosahexaenoic acid (DHA)(5 mg/kg) alone, or 1-palmitoyl-2-linoleil- sn -glycero-3-phosphoserine (PLPhtSer)(5 mg/kg) alone. POPhtCho (5 mg/kg) alone or DLPhtCho (5 mg/kg) plus POPhtCho (5 mg/kg) also significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine, but otherwise no significant effect was obtained with DLPhtCho (5 mg/kg) alone, AA (5 mg/kg) alone, DHA (5 mg/kg) alone, or PLPhtSer (5 mg/kg) alone. Oral co-administration with DLPhtCho (5 mg/kg) and POPhtCho (5 mg/kg) significantly shortened the acquisition latency for rats untreated with scopolamine as compared with the latency for administration with polyethylene glycol (PEG), DLPhtCho alone at doses of 5 and 10 mg/kg, or POPhtCho alone at doses of 5 and 10 mg/kg, while no efficient effect on the retention latency was obtained. To assess the effect of DLPhtCho and POPhtCho on cognitive functions for humans, Mini Mental State Examination (MMSE) test was performed in subjects with cognitive disorders (the average MMSE score, 15). Oral co-intake with DLPhtCho (50 mg) and POPhtCho (45 mg) once after breakfast everyday raised the score to over 20, corresponding to normal cognitive functions, throughout 5 months after intake, and the increase in the score was significantly greater than that for oral intake with DLPhtCho (100 mg/day) alone or POPhtCho (90 mg/kg) alone. Taken together, the results of the present study show that co-intake with DLPhtCho and POPhtCho could enhance learning and memory ability and improve cognitive disorders for both the animals and humans with a promising efficacy.     

丙烯腈对大鼠外周血淋巴细胞DNA损伤的研究

［目的］ 探讨丙烯腈对大鼠外周血淋巴细胞ＤＮＡ的损伤作用。［方法］ 在急性和亚急性经口染毒试验中,采用单细胞凝胶电泳技术检测不同染毒剂量（１０ｍ ｇ／ｋｇ、３０ｍ ｇ／ｋｇ 和５０ｍ ｇ／ｋｇ）丙烯腈（ＡＣＮ）及不同染毒时段（２ｈ、１４ｄ、２８ｄ、和４２ｄ）对大鼠淋巴细胞ＤＮＡ 的损伤情况。［结果］ 在急性和亚急性染毒试验中,大鼠淋巴细胞ＤＮＡ损伤程度均随ＡＣＮ 染毒剂量增大或染毒时间延长而逐渐加重,并显著高于对照组或染毒１４ｄ 组（Ｐ＜０．０１）,且存在较好的剂量－反应和时间－反应关系（Ｐ＜ ０．０１）。亚急性染毒试验中,随着染毒剂量的升高和染毒时间的延长,淋巴细胞ＤＮＡ 的损伤程度可达到饱和。染毒组细胞ＤＮＡ 损伤反应模式明显不同于对照组,单个细胞间的差异较大,且这种差异随染毒剂量增大和染毒时间延长也逐渐增大。［结论］ ＡＣＮ对大鼠外周血淋巴细胞ＤＮＡ具有明显的损伤作用,且损伤程度和模式受ＡＣＮ 染毒剂量和染毒时间的共同影响。     

2,5-己二酮染毒对大鼠坐骨神经雪旺氏细胞中S100β的影响

目的观察2,5-己二酮(2,5-hexanedione,HD)染毒致中毒性周围神经病变大鼠坐骨神经雪旺氏细胞中S100β蛋白与mRNA表达变化。方法将9周龄SPF级Wistar雄性大鼠分为3组,每组23只。HD低剂量和高剂量组经腹腔注射染毒给予100 mg/kg和300 mg/kg HD,连续8周,每周5次;对照组给予等体积生理盐水。各组处死10只大鼠并分离坐骨神经,采用免疫组化方法检测S100β蛋白表达和实时定量聚合酶链式反应方法观察mRNA表达,另取3只大鼠分离坐骨神经用于电镜观察。其余30只大鼠停止染毒、自然恢复8周后取材。结果染毒8周后高剂量组动物后肢全部瘫痪,低剂量组动物步态异常如后肢肌力下降。电镜观察染毒组动物坐骨神经髓鞘的形态异常。低、高剂量组中S100β表达量分别为对照组的92%和79%,染毒终止、恢复8周后为149%(P<0.05)和119%。染毒8周时S100βmRNA表达水平均降低,为对照组的0.65倍(P<0.05)和0.56倍(P<0.05),染毒终止、恢复8周后分别为1.46倍和0.87倍。结论 HD染毒大鼠中毒性周围神经病变坐骨神经雪旺氏细胞中S100β蛋白和mRNA表达发生变化,S100β蛋白参与了中毒性周围神经病变发生。     

Effects of lithium on peripheral neuropathy induced by vincristine in rats

Vincristine (VCR) as a frequently used antimitotic agent which is commonly prescribed for wide spectrum of neoplasm, causes mixed sensorimotor neuropathy. Several evidences show lithium could be a neuroprotective agent, therefore to assess whether a pretreatment and at subtherapeutic dose it could prevent the peripheral neuropathy produced by VCR, rats were treated with VCR 0.1mg/kg i.p. for 3 alternative doses and / or lithium chloride (20mg/kg or 40 mg/kg i.p. daily from the first day to the day of sacrifice). Erythrocyte lithium concentration (ELC) and plasma lithium concentration (PLC) were measured at the seventh day of study and the day of scarification. After seventh day of lithium administration, PLC and ELC reached to a steady state at subtheraputic dose and they did not significantly change at normal housing situation. Hot plate, open field test and nerve conduction velocity were used to evaluate the sensory and motor neuropathy. Only VCR treated rats showed behavioral, electrophysiological and histological evidences of a mixed sensorimotor neuropathy by significant increase in hot plate latencies and a marked decrease in total distance moved and conduction velocities in both sensory and motor nerves. Lithium at the dose of 20mg/kg and specially 40mg/kg robustly reduced the rate of mortality, general toxicity and was able to ameliorate mixed sensorimotor neuropathy induced by VCR. These results suggest that lithium at dose of 20mg/kg and 40 mg/kg, potentially by its effects on cell survival pathways such as inhibition of glycogen synthase kinase-3 (GSK3β), can prevent both motor and sensory components of VCR neuropathy.     

矽宁治疗实验性矽肺的剂量-效应关系研究

观察了不同剂量组的矽宁(2.5、5、10、20mg/kg)对大鼠实验性矽肺的疗效关系,疗程1个月。实验结果表明,各治疗组的全肺干重及胶原蛋白含量均明显低于矽肺对照组(P<0.01),表明该药具有明显抑制矽肺病变进展的作用。各治疗组随着矽宁给药剂量的增加,其全肺胶原蛋白含量相应降低,呈明显的负相关(r=-0.99)。矽宁经口半数致死量为1960mg/kg,经口半数有效量为2.4mg/kg,治疗指数为816。     

Nutritional rehabilitation of mitochondrial aberrations in aplastic anaemia

Aplastic anaemia (AA) is a disease characterised by bone marrow hypocellularity and peripheral blood pancytopenia. AA is also associated with mitochondrial aberrations. The present study was undertaken primarily to test the hypothesis that a nutrient mixture could affect the nutritional rehabilitation of mitochondrial aberrations in AA mice. BALB/c AA mice were induced by a combination of hypodermic injections of acetylphenylhydrazine (100?mg/kg), X-rays (2·0?Gy) and intraperitoneal injections of cyclophosphamide (80?mg/kg). We treated these mice with nutrient mixture-supplemented diets in a dose-dependent manner (1445·55, 963·7, 674·59?mg/kg per d), and the effects of the nutrient mixture for mitochondrial rehabilitation were analysed in AA mice. Transmission electron microscopy showed that mitochondrial ultrastructural abnormalities in bone marrow cells, splenocytes and hepatocytes of the nutrient mixture groups were restored markedly, compared with the AA group. Mitochondrial membrane potentials of the nutrient mixture groups were increased remarkably. Western blot analysis also revealed that the nutrient mixture significantly inhibited cytochrome c release of mitochondria in the AA group. Furthermore, the mitochondrial DNA content of the nutrient mixture groups was also increased. Our data suggest that the nutrient mixture may promote the rehabilitation of mitochondrial aberrations, and consequently protects against mitochondrial dysfunction in AA mice.