PAS—Na治疗锰中毒大鼠中枢神经系统病变的观察

利用光镜积电镜观察了染锰（ＭｎＣｌ２．４Ｈ２Ｏ，１５ｍｇ／ｋｇ）４，８，１６周及经ＰＡＳ－Ｎａ（１２０ｍｇ／ｋｇ）治疗后的大鼠中枢神经系统的病理表现。结果表明，染锰４周后大脑锥体细胞树突束即减少；随染锰时间延长，其减少更甚。染锰１６周后，大脑神经细胞溶酶体数量增加。此外，还观察到神经细胞核仁边移和核膜内陷（大脑皮质），核染色边储和核膜受损（尾壳核）的表现。经ＰＡＳ－Ｎａ治疗后，树突棘数有所恢复，发     

对氨基水杨酸钠对染锰大鼠睾丸病变影响的研究

给大鼠腹腔注射ＭｎＣｌ＿２·４Ｈ＿２Ｏ１５ｍｇ·ｋｇ￣（－１）·ｄ￣（－１），分期分别为４、８、１６周，然后给予ＰＡＳ－Ｎａ１２０ｍｇ·ｋｇ￣（－１）·ｄ￣（－１）３周，用光镜和电镜观察其对睾丸组织病理改变的影响。结果发现，染锰３周后，大鼠睾丸部分曲细精管表现管腔变窄，精细胞呈不规则状，各级精细胞减少，管腔内精子少或无。支持细胞底部溶酶体增多。随着染锰时间延长（１６周），睾丸的损害愈益严重，睾丸脏器系数明显小于对照组（Ｐ＜０．０５）。经ＰＡＳ－Ｎａ治疗后，精细胞中出现溶酶体，但无变性坏死的表现。在光镜下除见极少萎缩的曲细精管外，其余基本恢复正常，提示ＰＡＳ－Ｎａ可拮抗锰对睾丸的损害。     

PAS一Na对染锰雄性大鼠生殖毒性影响的研究

给大鼠染锰（ＭｎｃＬ＿２·４Ｈ＿２Ｏ，１５ｍｇ／ｋｇ／ｄ，ｉｐ）４、８周，再用ＰＡＳ一Ｎａ（１２０ｍｇ／ｋｇ／ｄ，ｉｐ）治疗３周后，通过光、电镜观察ＰＡＳ一Ｎａ对染锰雄性大鼠生殖毒性的影响。结果表明，染锰４、８周大鼠睾丸的支持细胞中溶酶体增加。此外，在染锰８周大鼠的睾丸中还观察到各级精细胞减少，细胞核呈不规则性改变。在光镜下也观察到曲细精管变性的表现，受损严重者，仅残存支持细胞和少量的精细胞，管腔中的精子消失。附睾尾的精子密度明显降低，精子畸形率升高。经ＰＡＳ一Ｎａ治疗后，睾丸病理组织学的表现恢复正常，精子数上升到正常水平，精子畸形率降低。提示ＰＡＳ一Ｎａ可拮抗锰的雄性生殖毒性。     

急性铬化物暴露肺损伤的剂量效应与时间过程

经一次气管灌注不同剂量可溶性六价铬酸钠（Ｎａ２ＣｒＯ４）后第２天和一次灌注０．９８ｍｇ·ｋｇ－１Ｎａ２ＣｒＯ４后不同时间，观察了ＳＤ大鼠支气管肺泡灌洗液（ＢＡＬＦ）和血液生化改变的剂量效应与时间过程。结果表明，Ｎａ２ＣｒＯ４的无效应剂量与阈剂量分别为０．００８和０．０４ｍｇ·ｋｇ－１，染毒剂量≥０．２０ｍｇ·ｋｇ－１时，ＢＡＬＦ中绝大多数生化参数呈现显著的剂量依赖性增加；严重中毒剂量（≥０．９８ｍｇ·ｋｇ－１）可引起ＢＡＬＦ和血液中几乎所有测试参数的显著增加，这种现象约持续一周，至少需要４周才能恢复正常。分析本次研究结果，可得出以下结论：≥０．９８ｍｇ·ｋｇ－１的Ｎａ２ＣｒＯ４可导致包括肺内细胞损伤、弥漫性肺泡炎和肺水肿在内的急性肺损伤；Ｎ－乙酰－β－Ｄ－氨基葡糖苷酶（ＮＡＧ）、溶菌酶（ＬＹＳ）、碱性磷酸酶（ＡＬＰ）、白蛋白（ＡＬｂ）和血管紧张素转换酶（ＡＣＥ），可能是评价接触较低剂量Ｎａ２ＣｒＯ４（＜０．９８ｍｇ·ｋｇ－１）后所致急性肺损伤的最有价值的早期敏感指标     

PAS——Na对染锰雄性大鼠生殖毒性影响的研究

给大鼠染锰４、８周，再用ＰＡＳ－Ｎａ治疗３周后，通过光、电镜观察ＰＡＳ－Ｎａ对染锰雄性大鼠生殖毒性的影响。结果表明，染锰４、８周大鼠睾丸的支持细胞中溶酶体增加。此外，在染凶８周大鼠的睾丸中还观察到各级精细胞减少，细胞核呈不规则性改变。在光镜下也观察到曲细精管变性的表现，受损严重者，仅残存支持细胞和少量的精细胞，管腔中的精子消失。附睾尾的精子密度明显降低，精子畸形率升高。经ＰＡＳ－Ｎａ治疗后，睾丸病     

刺梨利康饮排锰效果的实验研究

刺梨利康饮是本室以刺梨汁为主要原料研制的排重金属饮料。Ｗｉｓｔａｒ大鼠每日１次腹腔注射１５ｍｇ／ｋｇ二氯化锰后制成锰中毒模型，根据血锰水平随机分为单纯锰中毒组、饮用利康饮组和每日１次腹腔注射１２０ｍｇ／ｋｇ对氨基水杨酸钠（ＰＡＳ－Ｎａ）组，另设空白对照组。结果发现：锰中毒可增加机体锰负荷量和升高体内铜含量，降低体内锌含量；利康饮可显著增加粪锰排出量，降低血清和脑组织锰含量，并可补充血清和脑组织锌的含量；而ＰＡＳ－Ｎａ虽有排锰效果，但无补充微量元素作用。结果表明：刺梨利康饮具有一定排锰效果，降低机体的锰负荷，并具有补充微量元素的作用。     

醋酸铅对大鼠血压,心肌细胞膜Na泵及Ca泵活性的影响

对雄性ＳＤ大鼠用醋酸铅（ＰｂＡｃ）５０００ｍｇ／ｋｇ急性灌胃，对血压无影响，而致心肌细胞膜Ｎａ泵活性下降，Ｃａ泵活性升高，尿肌酐降低，肾肿大。实验表明大鼠每天染毒１０、３０、９０ｍｇ／ｋｇＰｂＡｃ９周，呈剂量－潜伏期和剂量－效应关系，使ＳＢＰ升高。各染毒组４～９周ＳＢＰ稳定上升，血铅、尿铅和心肌细胞膜Ｃａ泵活性、胸主动脉Ｃａ含量增高，心肌细胞膜Ｎａ泵活性降低，但对ＤＢＰ、肾重和尿肌酐含量无影响。提示低铅使心肌细胞膜Ｎａ泵活性降低，ＳＢＰ升高在早期铅中毒性心血管毒作用中具有重要意义。     

锰对大鼠甲状腺,肾上腺皮质功能影响研究

大鼠经腹腔注射ＭｎＣＬ２染毒３０天后，分别测定各染毒组（８、１６、２４ｍｇ／ｋｇ体重）及对照组血清ＦＴ３、ＦＴ４、ＴＳＨ、Ｆ的含量，结果：对照组ＦＴ３为８．６０７３．６５９Ｐｍｏｌ／Ｌ，２４ｍｇ／ｋｇ组ＦＴ３为４。８４９２．１３４Ｐｍｏｌ／Ｌ明显低于对照组（Ｐ＜０．０５）；血清中Ｆ含量对照组大鼠为５２．８９１８．４４ｎｍｏｌ／Ｌ。１６ｍｇ／ｋｇ，２４ｍｇ／ｋｇ体重组分别为４０．５７８．４８ｎｍｏｌ／Ｌ和３７．９１１０．１１ｎｍｏｌ／Ｌ，明显低于对照组（Ｐ＜０．０１），且有明显的剂量效应关系。说明锰在一定程度上损害了甲状腺及肾上腺皮质的功能。     

硒的化学形态对大鼠肝T45‘—脱单碘酶活力的影响

用低硒地区施硒肥（Ｎａ２ＳｅＯ３）粮饲料（Ｓｅ０．１００ｍｇ／ｋｇ）和硒含量相近的补硒（Ｎａ２ＳｅＯ３）粮饲料（Ｓｅ０．０９９ｍｇ／ｋｇ）分别喂养大鼠８周，观察不同化学形态硒对动物肝Ｔ４５＇－脱单碘酶（ＩＤ－Ｉ）活力、肝含量及血谷胱甘肽地氧化物酶（ＧＳＨ－Ｐｘ）活力的影响。结果表明，硒肥粮组与补硒粮组相比较，肝ＩＤ－Ｄ活性明显高（Ｐ＜０．０１），肝硒含量亦主同，但没有显著意义，而血ＧＳＨ－Ｐｘ活力     

锰对新生鼠脑组织热应激蛋白合成的影响

目的研究大鼠染锰后对其子代新生鼠脑组织热应激蛋白合成的影响。方法雌性大鼠随机分为４组,腹腔注射氯化锰两周,隔日一次,剂量分别为０、７５、１５、３０ｍｇ／ｋｇ;受孕后以同样方法继续染锰一周。分娩后对其新生鼠脑组织用ｗｅｓｔｅｒｎ斑点印迹法检测热应激蛋白７０,并测定超氧化物歧化酶（ＳＯＤ）。结果与对照组相比,ＳＯＤ活性在各组间差异无显著意义（Ｐ＞００５）;热应激蛋白７０,３０ｍｇ／ｋｇ组明显高于对照组（Ｐ＜００１）,７５和１５ｍｇ／ｋｇ组略有增加,但差异无显著意义（Ｐ＞００５）。结论亲代高剂量染锰可诱导子代新生鼠脑组织热应激蛋白７０合成增高,但这种效应在锰的胚胎毒性中的作用和机理仍有待进一步阐明。     

对氨基水扬酸钠对染锰小鼠免疫功能的影响

为了探讨对氯基水杨酸钠(PAS-Na)治疗锰中毒的作用机理,给小鼠每天ip Mncl_2(0、10、20、40mg/kg)染毒,4周后给予PAS-Na(120mg/kg),连续2周。结果表明;PAS～Na能增加脾NKC活性,增强T细胞功能。PAS-Na可能通过驱出体内的锰或与锰拮抗.恢复部分细胞免疫功能。     

对氨基水杨酸钠对染锰大鼠基底核氨基酸类神经递质含量的影响

目的 探讨对氨基水杨酸钠(PAS-Na)对亚急性染锰大鼠基底核γ-氨基丁酸(GABA)、谷氨酸(Glu)、谷氨酰胺(Gln)和片氨酸(Gly)等氨基酸类神经递质水平的影响.方法 将40只SD大鼠按完全随机法分为染锰组、低剂量(L-)PAS-Na(PAS)治疗组、高剂量(H-)PAS治疗组和正常对照组,每组10只.给染锰、L-PAS和H-PAS治疗组腹腔注射MnCl2·4H2O 15 mg/kg,对照组腹腔注射等容量生理盐水,每日 1次,每周5 d,共4周.分别给L-PAS治疗组、H-PAS治疗组背部皮下注射PAS-Na 100、200mg/kg,其余组背部皮下注射等容量生理盐水,每日1次,连续3周和6周.用高效液相色谱荧光检测法测定大鼠基底核Glu、Gln、Gly及GABA含量.结果 PAS-Na治疗3周时,染锰组Gly[(0.165±0.022)μmol/g]含量比对照组[(0.271±0.074)μmol/g]低(t=4.65,P＜0.05).PAS-Na治疗6周时,染锰组Glu、Gln和Gly含量[依次为(0.942±0.121)、(0.377±0.070)、(0.142±0.048)tμmol/g]均比对照组低[依次为(1.590±0.302)、(0.563±0.040)、(0.247±0.084)μmol/g;t值分别为7.72、5.85、4.30,P值均＜0.05];L-PAS治疗组、H-PAS治疗组Glu、Gln和H-PAS组Gly含量[依次为(1.268±0.124)、(1.465±0.196)、(0.497±0.050)、(0.514±0.103)、(0.219±0.034)μmol/g]均比染锰组高(L-PAS组Glu、Gln与染锰组比较,t值分别为3.89、3.77,P值均＜0.05;H-PAS组Glu、Gln、Gly与染锰组比较,t值分别为6.78、4.70、3.42,P值均＜0.05).结论 锰对大鼠基底核Glu、Gln和Gly的毒作用明显,以对Gly的毒性影响出现较早,脱离锰暴露后其毒性影响仍然继续发展.PAS-Na对锰的Glu、Gln和Gly毒性影响可能有拮抗作用.

Abstract：

Objective To probe the effect of sodium para-aminosalicylate (PAS-Na) on concentration of amino acid neurotransmitters including glutamate ( Glu), glutamine ( Gln ), glycine (Gly) and gamma-aminobutyric acid (GABA) in basal ganglia of subacute manganese (Mn)-exposed rats. Methods Forty Sprague-Dawley male rats were randomly divided into the control, Mn-exposed, low dose PAS-Na (L-PAS) and high dose PAS-Na (H-PAS) groups. Rats in experiment groups received daily intraperitoneally injections of manganese chloride (MnCl2 · 4H2O, 15 mg/kg), while rats in control group received daily intraperitoneally injections of normal saline (NS),all at 5 days/week for 4 weeks. Then the rats in PAS groups followed by a daily subcutaneously dose of PAS-Na ( 100 and 200 mg/kg as the L-PAS and H-PAS groups,respectively) for another 3 and 6 weeks; while the rats in Mn-exposed and control group received NS. The concentrations of Glu,Gln,Gly and GABA in basal ganglia of rat was detected by the high performance liquid chromatography fluorescence detection technique. Results After treating with PAS-Na for 3 weeks, the concentration of Gly in the Mn-exposed rats decreased to (0. 165 ± 0.022)μmol/L ( control = (0. 271 ±0. 074 ) μmol/L, Mn vs control, t = 4. 65, P ＜ 0. 05 ). After the further 6-week therapy with PAS-Na,the concentrations of Glu,Gln,Gly in the Mn-exposed rats were lower than those of the control rats ((0.942 ±0. 121 ), (0.377 ±0.070), (0. 142 ±0.048), ( 1.590 ± 0. 302), (0.563 ±0.040),(0. 247 ± 0. 084) μ mol/L; t = 7.72,5.85,4. 30, P ＜ 0. 05 ); and also lower than in L-PAS and H-PAS groups, whose concentrations were seperately ( 1. 268 ± 0. 124 ) , ( 1. 465 ± 0. 196 ), ( 0. 497 ± 0. 050 ),(0. 514 ±0. 103 ), (0. 219 ±0. 034) μmol/L ( L-PAS Glu and Gln vs Mn ,t = 3. 87,3. 77 ,P ＜0. 05; H-PAS Glu ,Gln and Gly vs Mn ,t = 6. 78,4. 70,3.42, P ＜ 0. 05 ). Conclusion The toxic effect of manganese on Glu,Gln and Gly in basal ganglia of Mn-exposed rats is obvious,especially appears earlier on Gly. The toxic effect still continues to develop when relieved from the exposure. PAS-Na may play an antagonism role in toxic effect of manganese on concentration of Glu, Gln and Gly in basal ganglia of Mn-exposed rats.     

锰对新生鼠肝组织HSP70合成的影响

雌性大鼠随机分为4组,腹腔注射氯化锰两周,隔日一次,剂量分为0、75、15、30mg/kg.受孕后以同样方法继续染锰一周.分娩后对其新生鼠肝组织用western斑点印迹法检测热应激蛋白70(HSP70),并测定其超氧化物歧化酶(SOD).发现15mg/kg组SOD活性低于对照组(P<0.05);HSP70含量,染锰各组明显高于对照组(P<0.01).提示亲代妊娠期染锰可诱导子代新生鼠肝组织HSP70合成增加,但这种效应在锰的胚胎发育毒性中的作用和机理仍有待进一步阐明.     

对氨基水杨酸钠对染锰大鼠肝和血清酶的影响

本文观察了80mg/kg和120mg/kg的PAS-Na对染锰大鼠肝和血清几种酶活性的影响。结果表明,两种剂量的PAS-Na能恢复肝ATPase(分别为95%和97%)以及血清ACP活性(分别为112%和83%);高剂量的PAS-Na有恢复血清AChE活性(89%)的作用。PAS-Na还能驱除肝锰。     

高脂饲料喂养时间及链脲佐菌素剂量对实验型2型糖尿病大鼠造模的影响

目的采用高脂饲料联合链脲佐菌素(STZ)诱导方法建立糖尿病大鼠模型,探讨模型死亡率和成模率的影响因素。方法 8周龄雄性Wistar大鼠在高脂饲料喂养0周、4周、6周或8周后分别腹腔注射30mg/kg STZ;雄性Wistar大鼠在高脂饲料喂养四周后分别腹腔注射20、30或60 mg/kg STZ建立糖尿病模型,做糖耐量实验及胰岛素耐量实验,并检测血清指标,然后再以罗格列酮作为阳性药物进行验证。结果大鼠在高脂饲料喂养4周后,腹腔注射STZ 30 mg/kg处理后,糖尿病大鼠模型成模率分别为85%和80%,高于20 mg/kg STZ组;死亡率为零,显著低于60 mg/kg STZ组(75%);高脂饲料喂养4周后注射30 mg/kg STZ组死亡率最低,而高脂饲料喂养8周模型组死亡率最高达65%。成模大鼠血清甘油三酯、游离脂肪酸显著升高(P<0.05),空腹血清胰岛素未明显下降,并出现糖耐量异常和胰岛素抵抗;罗格列酮治疗4周后血糖、血清甘油三酯及游离脂肪酸显著降低(P<0.05)。结论高脂饲料喂养时间、STZ剂量及鼠龄是影响糖尿病大鼠模型成模率和死亡率的重要因素。     

牛磺酸改善染锰大鼠学习记忆能力的海马蛋白质组学研究

目的通过双向电泳实验(2-dimensional gel electrophoresis,2-DE)研究牛磺酸减轻急性染锰诱导大鼠学习记忆损伤的分子机制。方法 60只SPF雄性SD大鼠随机分3组:生理盐水(NS)对照组,连续腹膜内注射(ip)0.9%NS;染锰组,每日ip MnCl2.4H2O(15mg/kg.d);牛磺酸预防组,染锰的同时ip牛磺酸(200 mg/kg.d),各组大鼠连续注射4w。最后一次干预结束后进行水迷宫实验观察大鼠学习记忆能力变化,分离大鼠海马组织并制备总蛋白,2-DE分离差异蛋白质并经辅助激光解析电离飞行时间质谱仪(MALDI-TOF-MS)分析和Mascot数据库检索鉴定差异蛋白。结果水迷宫实验显示:平均逃避潜伏时间(s)染锰组大鼠39.8±2.3,较对照组29.5±2.5及牛磺酸预防组29.4±2.3显著延长(P<0.05),平台搜索次数各组间无显著差异,染锰组与对照组、预防组比对共有10个差异表达的蛋白质斑点,鉴定出4个表达下调的蛋白质,分别是NADH dehydrogenase(ubiquinone)Fe-S protein 1、Galactokinase I、whaq protein、beta-centractin。结论牛磺酸对急性染锰诱导的大鼠空间学习能力损伤有明显改善作用,蛋白质组学研究初步鉴定出4个在三组中共存的表达下调蛋白质点。[营养学报,2012,34(6):553-557]     

Influence of zinc chloride on the metabolism and hepatotoxicity of bromobenzene in rats

In studying the possible interactive effects of various heavy metals on bromobenzene hepatotoxicity and metabolism, zinc chloride (ZnCl2) (0.5, 2.0, and 10.0 mg/kg) was given ip 24 hr prior to ip administration of bromobenzene (2.5 mmol/kg body wt). Animals were sacrificed 48 hr after bromobenzene. A significant increase in the activities of serum transaminases (serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) was observed at 0.5 mg/kg ZnCl2 and such an effect was not observed at the two higher doses of ZnCl2. However, no such increase in the transaminases activities was observed when rats were treated with identical doses of ZnCl2 48 hr before the administration of bromobenzene. When rats were treated with 2 mg/kg ZnCl2 6 hr prior to the bromobenzene dose, a potentiation of the hepatotoxicity due to bromobenzene was again observed, whereas simultaneous treatment of bromobenzene and ZnCl2 produced no such effect. Treatment with ZnCl2 (0.5 mg/kg) 24 hr prior to bromobenzene injection failed to modify the pattern of the urinary metabolites of bromobenzene. When rats were given 50, 250, or 500 ppm of ZnCl2 in drinking water daily for 4 weeks prior to an ip injection of 2.5 mmol/kg bromobenzene, a reduction in the activities of serum transaminases was observed in 250 ppm ZnCl2-treated rats only. Such a reduction in the hepatotoxicity of bromobenzene is accompanied by a simultaneous reduction of the in vivo metabolism of bromobenzene by zinc, as substantiated by reduction of its urinary thioethers as well as of its total urinary metabolites. The present study has shown that changes in the metabolism and hepatotoxicity of bromobenzene depend on the dose of zinc administered, as well as on the temporal relationship between the zinc and bromobenzene administrations. The definitive mechanism responsible for such interactions remains to be elucidated.     

Effectiveness of certain drugs in acute malathion intoxication in rats

The protective effects of atropine, diacetylmonoxime (DAM), and diazepam separately and in combination were investigated in rats exposed to malathion. Malathion (500 mg/kg, ip) inhibited acetylcholinesterase (AchE) activity in RBC and brain and produced hyperglycemia and hyperlactacidemia with depletion of glycogen in liver, triceps, and brain of animals 2 hr after its administration. Atropine (20 mg/kg, ip) given immediately after malathion abolished hyperglycemia and glycogenolytic effect but exhibited no effect on the recovery of inhibited AchE activity. DAM (100 mg/kg ip) given immediately after malathion significantly reactivated the inhibited AchE activity both in RBC and brain. It also partially modified hyperglycemia and glycogenolytic effect. Diazepam (50 mg/kg, ip) slightly modified AchE and abolished hyperglycemia, hyperlactacidemia, and glycogenolytic effects. A combination of these drugs protected the animals from the acute toxic effects of malathion.     

氯化锰染毒对大鼠肝脏亚细胞器微量元素含量的影响

目的探讨氯化锰(MnCl2)染毒对大鼠肝细胞核、线粒体、细胞膜微量元素的影响。方法雄性SD大鼠随机分为6组(30 d染毒组,90 d染毒组,90 d+30 d染毒组,30 d对照组,90 d对照组,90 d+30 d对照组),30 d染毒组和90 d染毒组分别经腹腔连续注射MnCl26 mg/(kg·d)(以Mn计)30 d、90 d(周日除外);90 d+30 d染毒连续注射MnCl290 d后停止染毒,继续正常喂养30 d。使用电感耦合等离子体-质谱(ICP-MS)仪测量大鼠肝细胞核、线粒体、细胞膜中Mn、Ca、Cu、Mg、Fe、Zn的含量。结果细胞核和细胞膜中的微量元素在染毒90 d后分别有不同程度的升高,线粒体中的微量元素除Mn和Ca元素含量显著升高外,均显著降低。结论肝细胞线粒体是Mn蓄积的主要场所,Mn对大鼠肝脏的损伤作用主要表现在对线粒体的损伤作用,染Mn后线粒体Cu、Fe、Zn、Mg含量降低,可能是Mn中毒引起肝线粒体损害的机制之一。