对氨基水杨酸钠对染锰大鼠脑酶的影响

每日给大鼠腹腔内注射(ip)15mg/kg/d MnCl_2·4H_2O60天,然后分别以80mg/kg/d。120mg/kg/d PAS-Na ip治疗16天。结果提示,PAS-Na能不同程度地恢复部分脑区受锰抑制的ACP和ATPase活性及各脑区的AchE活性,其中以120mg/kg/d剂量的作用更为明显。治疗结果表明,PAS-Na的作用机理可能在于其能恢复被锰抑制的有关酶活性,从而恢复神经细胞的正常功能和降低中枢胆碱能的突触功能。     

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。     

对氨基水杨酸钠对亚慢性染锰大鼠基底前脑胆碱能神经细胞的影响

[目的]探讨对氨基水杨酸钠(PAS-Na)对亚慢性染锰大鼠基底前脑胆碱能神经细胞的影响. [方法]48只雄性SD大鼠被随机分为对照Ⅰ、Ⅱ组,染锰Ⅰ、Ⅱ组,PAS-Na预防(预防)组,PAS-Na治疗(治疗)组,每组8只.染锰组、预防组、治疗组大鼠每日腹腔注射氯化锰(MnCl2·4H20 15 mg/kg),每周5d,对照组腹腔注射等容量生理盐水,预防组在染锰同时每日背部皮下注射PAS-Na(200 mg/kg),连续12周.13周开始,治疗组每日背部皮下注射PAS-Na(200 mg/kg),同时染锰Ⅱ组、对照Ⅱ组背部皮下注射等容量生理盐水至18周.采用水迷宫实验检测大鼠学习记忆能力,免疫组化染色观察胆碱乙酰转移酶(ChAT)阳性神经元形态及数量,检测基底前脑ChAT蛋白活性. [结果]12周后,染锰组逃避潜伏期、游泳路程均比对照Ⅰ组长,预防组逃避潜伏期、游泳路程均较染锰组短(P＜0.05).染锰组基底前脑垂直支臂核(vDB)/水平支臂核(hDB)ChAT阳性细胞数较对照Ⅰ组少,预防组vDB/hDB ChAT阳性细胞数较染锰组多(P＜0.05);染锰组大鼠基底前脑组织ChAT蛋白活性较对照Ⅰ组低,预防组较之回升(P＜0.05).18周后,染锰组逃避潜伏期、游泳路程都比对照组长,治疗组逃避潜伏期、游泳路程比染锰组短(P＜0.05).染锰组vDB/hDB ChAT阳性细胞数较对照组少,治疗组vDB ChAT阳性细胞数较染锰Ⅱ组多(P＜0.05). [结论]PAS-Na对亚慢性染锰引起大鼠基底前脑ChAT阳性细胞减少、ChAT蛋白活性降低和学习记忆障碍可能有拮抗作用.     

对氨基水杨酸钠对染锰大鼠学习记忆及海马GFAP阳性细胞表达的影响

目的 探讨对氨基水杨酸钠(PAS-Na)对亚急性染锰大鼠学习记忆及海马胶质原纤维酸性蛋白(GFAP)阳性细胞表达的影响.方法 雄性SD大鼠40只随机分为正常对照组(对照组)、染锰组、低和高剂量PAS-Na治疗组(L-、H-PAS组).染锰和PAS治疗大鼠每天腹腔注射(ip)MnCl2·4H2()15 mg/kg,对照组...     

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.     

锰对大鼠生精细胞凋亡的影响

目的研究氯化锰对大鼠生精细胞凋亡的影响,探讨锰诱发生精细胞凋亡的机制。方法24只健康雄性SD大鼠随机分为3组。锰染毒组给MnCl2.4H2O(15 mg/kg,30 mg/kg)4周,对照组给予生理盐水,各组给药途径为腹腔注射,1次/d,5 d/周。应用原位末端脱氧核苷酸转移酶标记(TUNEL)技术检测睾丸生精细胞凋亡;免疫组化法检测生精细胞p53和Bcl-2蛋白的表达;化学比色法检测睾丸组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)活力。结果生精细胞凋亡指数(apoptosis index,AI)在锰染毒15 mg/kg组为(1.05±0.19)%,锰染毒30 mg/kg组为(1.80±0.21)%,均明显高于对照组(0.48±0.01)%(P<0.01);p53阳性细胞率在锰染毒15 mg/kg组为(9.83±1.15)%,锰染毒30 mg/kg组为(18.23±2.15)%,均明显高于对照组(3.72±0.35)%(P<0.01);锰染毒30 mg/kg组Bcl-2阳性细胞率(21.26±2.50)%明显低于对照组(52.46±3.57)%和锰染毒15 mg/kg组(51.34±3.87)%(P<0.01)。锰染毒组睾丸组织SOD、CAT及GSH-Px活力均明显低于对照组(P<0.01)。结论锰诱导的p53高表达、Bcl-2低表达以及抗氧化能力的下降可能是大鼠生精细胞凋亡增加的重要原因之一。     

染锰大鼠生精细胞Caspaes-3和Ki-67表达

目的 研究氯化锰对大鼠生精细胞半胱天冬酶(Caspase-3)和抗霍奇金淋巴瘤细胞核抗体(Ki-67)表达的影响及意义.方法 48只雄性SD大鼠随机分为6组:空白对照组,15和30 mg/kg MnCl2组,锰与生理盐水均为腹腔注射,1次/d,5 d/周,分别染锰4和6周.用免疫组化法检测睾丸生精细胞Caspase-3与Ki-67表达.结果 与空白对照组比较,各染锰组Caspase-3阳性细胞率均显著升高(P<0.01);染锰剂量相同,染锰6周组与4周组比较,Caspase-3阳性细胞率均显著升高(P<0.01);染锰时间相同,30 mg/kg MnCl2与15 mg/kg MnCl2组比较,Caspase-3阳性细胞率均显著升高(P<0.01).与空白对照组比较,染锰15 mg/kg MnCl24周组Ki-67阳性细胞率降低(P<0.05);染锰30 mg/kg MnCl2 4周组,15 mh/kg MnCl2 6周组,30 mg/kg MnCl2 6周组Ki-67阳性细胞率均显著降低(P<0.01);染锰时间相同,30 mg/kg MnCl2组与15 mg/kg MnCl2组比较,Ki-67阳性细胞率显著降低(P<0.01).各组大鼠生精细胞Caspase-3阳性细胞率与Ki-67阳性细胞率呈明显负相关(r=-0.798,P<0.01),结论染锰15 mg/kg 4周即可促进大鼠生精细胞Caspase-3表达和抑制大鼠生精细胞Ki-67表达,且存在一定的剂量-效应和时间-效应关系,锰的这种双重作用可能是导致大鼠生精障碍的主要机制.     

对氨基水杨酸钠对锰染毒大鼠丘脑原代小胶质细胞氧化损伤及炎症反应的影响

[目的]探讨对氨基水杨酸钠(PAS-Na)对体外染锰大鼠丘脑原代小胶质细胞氧化损伤、炎症反应的影响。[方法]将提纯、鉴定后的SD大鼠丘脑小胶质细胞分别给予含不同浓度氯化锰(MnCl_2)(0、200、300、400、500μmol/L)、PAS-Na(50、150、450μmol/L)的完全培养基(DMEM+FBS)培养24 h,采用MTT法检测细胞存活率,根据结果选择染锰的毒性剂量并选定PAS-Na的无毒剂量。随后将细胞随机分为对照组、400μmol/L MnCl_2组、400μmol/L MnCl_2+(50、150、450μmol/L)PAS-Na组、450μmol/L PAS-Na组,共6组。采用MTT法检测各组小胶质细胞存活率;运用DCFH-DA探针标记,荧光倒置显微镜下观察小胶质细胞内活性氧(ROS)的产生情况;ELISA法测定炎症因子白介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α的蛋白分泌量和荧光定量PCR法测IL-1β,TNF-αmRNA表达水平。[结果]400、500μmol/L MnCl_2染毒组的细胞存活率为(85.83±12.53)%、(83.30±6.33)%,低于对照组(均P0.05),故选择400μmol/L作为锰的染毒剂量;与对照组比较,50、150、450μmol/L PAS-Na组的细胞存活率无明显变化(均P0.05)。400μmol/L MnCl_2+(50、150、450μmol/L)PAS-Na组的细胞存活率分别为(96.00±18.11)%、(106.13±18.32)%、(110.21±15.13)%,均比400μmol/L MnCl_2组高(均P0.05)。与对照组比较,400μmol/L MnCl_2组细胞ROS水平、IL-1β和TNF-α的蛋白及mR NA表达水平均升高(均P0.05)。与400μmol/L MnCl_2组比较,400μmol/L MnCl_2+(50、150、450μmol/L)PAS-Na组的ROS水平、TNF-α分泌量和IL-1βmRNA表达量均降低(均P0.05),400μmol/L MnCl_2+(150、450μmol/L)PAS-Na组的TNF-αmRNA表达量降低(均P0.05)。[结论]PAS-Na可减轻锰致大鼠丘脑原代小胶质细胞氧化损伤、炎症反应的程度。     

对氨水杨酸钠诊断性治疗锰中毒1例报告

本文报道对氨水杨酸钠(PAS-Na)诊断性治疗锰中毒一例,经PAS-Na 8g/d,加入10%葡萄糖500ml中静脉滴注,连续用药4日,间隔停药3日为一疗程,共治疗6个疗程,用PAS-Na总量192g,患者症状和体征明显改善,为本例锰中毒的诊断提供了佐证。     

对氨基水杨酸钠干预锰致大鼠海马神经元损伤的体外研究

目的 探讨对氨基水杨酸钠(PAS-Na)体外染锰致大鼠原代海马神经元损伤的干预作用.方法 培养至第8天的海马神经元随机分为对照组、染锰组、低、中和高剂量PAS-Na干预组(L-PAS、M-PAS、H-PAS组).对照组给予培养液培养48 h;染锰组神经元暴露于MnCl2·4H2O 50/μmol/L培养液培养24 h后...     

PAS－Na治疗锰中毒大鼠中枢神经系统病变的观察

利用光镜和电镜观察了染锰（ＭｎＣｉ２·４Ｈ２Ｏ，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棘即减少；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），核染色质边集和核膜受损（尾壳核）的表现。经ＰＡＳ－Ｎａ治疗后，树突棘数有所恢复，发生了改变的神经细胞也基本恢复正常。提示ＰＡＳ－Ｎａ是一种治疗锰中毒的有效药物。     

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。     

A report of two cases of chronic serious manganese poisoning treated with sodium para-aminosalicylic acid.

Two cases of chronic manganese poisoning were treated with sodium para-aminosalicylic acid (PAS-Na; 6 g/day in 500 ml of 10% glucose solution by intravenous drip). The results indicated that one had been clinically cured and that the other had obviously improved in clinical symptoms and signs. Thus PAS-Na appears to be an effective drug for treatment of serious chronic manganese poisoning.     

A report of two cases of chronic serious manganese poisoning treated with sodium para-aminosalicylic acid.

Two cases of chronic manganese poisoning were treated with sodium para-aminosalicylic acid (PAS-Na; 6 g/day in 500 ml of 10% glucose solution by intravenous drip). The results indicated that one had been clinically cured and that the other had obviously improved in clinical symptoms and signs. Thus PAS-Na appears to be an effective drug for treatment of serious chronic manganese poisoning.     

Erythrocyte magnesium fluxes in mice with nutritionally and genetically low magnesium status

Summary Low intracellular magnesium (Mg) contents may be observed in case of severe Mg insufficient intake or because of genetic regulation. This work was conducted to investigate the influence of intracellular Mg content on erythrocyte Mg²⁺ influx and efflux in mice with low nutritionally and genetically (MGL and MGH mice) Mg status. C57BL6 mice were fed for 2 wks a diet containing 1000 mg Mg/kg diet Mg (control group), 100 mg Mg/kg diet (Mg–marginal group) or 30 mg Mg/kg diet (Mgdeficient group), while mice with low (MGL) and high (MGH) Mg levels were fed a control diet for 2 wks. The quantification of erythrocyte Mg²⁺ influx and efflux was performed using a stable isotope of Mg. Our results showed that erythrocyte Mg²⁺ influx and efflux were respectively increased and decreased in nutritional Mg deficiency; while in genetically determined Mg status Mg²⁺ fluxes were lower in MGL mice compared to MGH mice. Moreover Mg²⁺ efflux was significantly correlated to Mg level in erythrocytes in all the mice studied (p < 0.001). In conclusion, erythrocyte Mg²⁺ influx and efflux are modulated by low Mg status, namely decreased Mg²⁺ efflux compensate for nutritional Mg deficiency, while the genetic regulation of erythrocyte Mg²⁺ content depends on modification of Mg²⁺ influx.     

PAS-Na对染锰大鼠学习记忆及海马神经微丝蛋白表达的影响

[目的]探讨对氨基水杨酸钠（PAS．Na）对染锰大鼠学习记忆功能及神经微丝蛋白（NF）表达的影响。[方法]将48只雄性sD大鼠随机分为对照组、染锰组、PAS—Na低、高剂量治疗组（L—PAS、H．PAS）四组,染锰组、L-PAS组、H—PAS组大鼠每日腹腔注射（ip）氯化锰（MnCl2·4H2O,15mg／kg）,每周5d,共3周。然后,L-PAS、H—PAS组大鼠每日分别于背部皮下注射（sc）PATS．Na100mg／kg、200mg／kg,持续5周。采用Morris水迷宫检测大鼠学习记忆能力,免疫组织化学方法检测海马齿状回颗粒细胞下层微丝蛋白（NF）阳性细胞数。[结果]染锰组逃避潜伏期、游泳总路程均比正常对照组长（P〈0．05）;H．PAS组逃避潜伏期和游泳总路程比染锰组缩短（P〈0．05）。染锰组NF阳性细胞数比正常对照组减少（P〈0．01）,H．PAS组NF阳性细胞数较染锰组增多（P〈0．01）,但是仍达不到正常对照组水平（P〈0．01）。[结论]高剂量PAS—Na对锰致学习记忆能力及海马颗粒细胞受损可能有作用。     

Marginal protein intake results in reduced plasma IGF-I levels and skeletal muscle fiber atrophy in elderly women

We investigated the effects of dietary protein on plasma IGF-I levels and muscle fiber cross-sectional area (CSA). Twelve healthy elderly women were randomly assigned to a weight-maintaining diet containing either 1.47 (marginal) or 2.94 (adequate) g protein/kg body cell mass (BCM)/d, (0.45 and 0.92 g/kg body weight/d, respectively) for 10wks. Plasma IGF-I levels and muscle fiber areas and distributions were evaluated at baseline and 10wks. After 10wks, both IGF-I and type I fiber CSA had declined significantly in subjects fed the marginal diet (30.1+/-2.1% and 32.7+/-7.9%, respectively) while they increased in those fed the adequate diet (19.5+/-7.0% and 22.3+/-7.5%, for IGF-I and type I CSA, respectively). The change in IGF-I was the only significantly associated with the change in type I fiber CSA (r2=0.70; p<0.03). These findings show that marginal dietary protein intakes will result in losses of muscle mass in the elderly and suggest a role for plasma IGF-I as a biochemical marker for the histological changes in skeletal muscle.