镉对雄性大鼠脊髓下腰段运动神经元的影响
摘要
目的:研究镉对大鼠脊髓下腰段 SNB 和 DLN 运动神经元的影响
方法:成年雄性 Wistar 大鼠随机分成对照组、单纯镉组和镉加雄激素组。单纯镉组和镉加雄激素组给于腹腔内反复小剂量注射氯化镉(按 0.5mg/kg 体重和 1.0mg/kg 体重剂量,每 4d 交替注射一次,从0.5mg/kg 体重剂量开始注射)。取材前 2h,镉加雄激素组给于 TP 500μg皮下注射。灌流前经心脏采血测定血清睾酮的含量,灌流固定后取脊髓 L5-6节段进行 SNB 和 DLN 运动神经元 AR 免疫组化、光密度以及神经元胞体形态计量学分析,透射电镜观察脊髓 SNB 和 DLN 运动神经元超微结构的变化,同时采用原子吸收石墨炉法测定脊髓镉含量。
结果:染镉后 7d、10d、15d、30d,脊髓内镉含量升高。血清睾酮水平与正常比较,无显著性差异,但 30d 时血清睾酮水平下降趋势明显。染镉 7d、10d、15d,神经元细胞核内 AR 免疫阳性染色较正常组浅淡,平均光密度值降低,TP 500μg 皮下注射 2h,AR 免疫染色强度无明显加强;染镉 30d 时,AR 免疫染色强度进一步降低,平均光密度值比 7d、10d、15d 组更为降低,TP 500μg 皮下注射 2h,AR 免疫染色强度增强,但是只达到单纯染镉 7d、10d、15d 组水平。染镉后,神经元细胞内溶酶体明显增多,细胞胞体平均截面积无改变。
Objective: To investigate the effects of cadmium ( Cd ) onandrogen-dependent SNB and DLN spinal motoneurons in adult male rats
Methords: Adult, male Wistar rats were divided into three groups byrandom selection: Control, Cd, Cd+TP. Cd and Cd+TP groups were treatedintraperitoneally with cadmium chloride (CdCl2) at the alternate dose of 0.5or 1 mg/kg body weight every 4th day, starting with 0.5 mg/kg bw. Theanimals of Cd+TP groups was sacrificed 2h after 500μg TP (testosteronepropionate) subcutaneous injection. Ultrastructure, androgen receptor (AR)immunochemistry and average optical intensity of AR immunoreactivity,and the mean somatic areas of motoneurons in the SNB and DLN, serumtestosterone levels, and cadmium accumulation in the spinal cord werestudied.
Results: The content of Cd in spinal cord increased significantlyafter Cd exposure. No significant differences were detected in serumtestosterone levels after 7, 10, 15, 30 days of Cd administration. However,the serum testosterone levels at 30 days showed an obviously decreasingtrend as compared with control. In SNB and DLN motoneurons, ARimmunoreactivity was reduced after 7, 10, 15 days of Cd treatment. No
recovery was seen after TP injection. AR immunoreactivity was decreasedsignificantly after 30 days and recovered partly after TP injection. Therewere no significant differences in the mean somatic areas of motoneuronsin the SNB and DLN. Only the increased lysosomes were seen in the SNBand DLN motoneurons at the ultrastructural level after Cd administration.
Conclusion: With alternate, low dose Cd exposure, Cd can deposit inspinal cord of male rats. It can cause the changes of the function andstructure of the SNB and DLN motoneurons,
方法:成年雄性 Wistar 大鼠随机分成对照组、单纯镉组和镉加雄激素组。单纯镉组和镉加雄激素组给于腹腔内反复小剂量注射氯化镉(按 0.5mg/kg 体重和 1.0mg/kg 体重剂量,每 4d 交替注射一次,从0.5mg/kg 体重剂量开始注射)。取材前 2h,镉加雄激素组给于 TP 500μg皮下注射。灌流前经心脏采血测定血清睾酮的含量,灌流固定后取脊髓 L5-6节段进行 SNB 和 DLN 运动神经元 AR 免疫组化、光密度以及神经元胞体形态计量学分析,透射电镜观察脊髓 SNB 和 DLN 运动神经元超微结构的变化,同时采用原子吸收石墨炉法测定脊髓镉含量。
结果:染镉后 7d、10d、15d、30d,脊髓内镉含量升高。血清睾酮水平与正常比较,无显著性差异,但 30d 时血清睾酮水平下降趋势明显。染镉 7d、10d、15d,神经元细胞核内 AR 免疫阳性染色较正常组浅淡,平均光密度值降低,TP 500μg 皮下注射 2h,AR 免疫染色强度无明显加强;染镉 30d 时,AR 免疫染色强度进一步降低,平均光密度值比 7d、10d、15d 组更为降低,TP 500μg 皮下注射 2h,AR 免疫染色强度增强,但是只达到单纯染镉 7d、10d、15d 组水平。染镉后,神经元细胞内溶酶体明显增多,细胞胞体平均截面积无改变。
Objective: To investigate the effects of cadmium ( Cd ) onandrogen-dependent SNB and DLN spinal motoneurons in adult male rats
Methords: Adult, male Wistar rats were divided into three groups byrandom selection: Control, Cd, Cd+TP. Cd and Cd+TP groups were treatedintraperitoneally with cadmium chloride (CdCl2) at the alternate dose of 0.5or 1 mg/kg body weight every 4th day, starting with 0.5 mg/kg bw. Theanimals of Cd+TP groups was sacrificed 2h after 500μg TP (testosteronepropionate) subcutaneous injection. Ultrastructure, androgen receptor (AR)immunochemistry and average optical intensity of AR immunoreactivity,and the mean somatic areas of motoneurons in the SNB and DLN, serumtestosterone levels, and cadmium accumulation in the spinal cord werestudied.
Results: The content of Cd in spinal cord increased significantlyafter Cd exposure. No significant differences were detected in serumtestosterone levels after 7, 10, 15, 30 days of Cd administration. However,the serum testosterone levels at 30 days showed an obviously decreasingtrend as compared with control. In SNB and DLN motoneurons, ARimmunoreactivity was reduced after 7, 10, 15 days of Cd treatment. No
recovery was seen after TP injection. AR immunoreactivity was decreasedsignificantly after 30 days and recovered partly after TP injection. Therewere no significant differences in the mean somatic areas of motoneuronsin the SNB and DLN. Only the increased lysosomes were seen in the SNBand DLN motoneurons at the ultrastructural level after Cd administration.
Conclusion: With alternate, low dose Cd exposure, Cd can deposit inspinal cord of male rats. It can cause the changes of the function andstructure of the SNB and DLN motoneurons,
引文
[1] 刘杰. 镉的毒性和毒理学研究进展[J]. 中华劳动卫生职业病杂志, 1998, 16(1): 2-4
[2] 许舸,徐晨. 镉对中枢神经系统影响的研究进展[J]. 国外医学卫生学分册, 2005, 32(1):19-24
[3] Volchegorskii IA, Telesheva IB, Turygin VV. Age-related changes in cadmium content and oxidative modification of proteins in different regions of human spinal cord[J]. Bull Exp Biol Med, 2004, 137(5):440-442.
[4] Murphy VA, Embrey EC, Rosenberg JM, et al. Calcium deficiency enhances cadmium accumulation in the central nervous system[J]. Brain Res, 1991, 557(1-2):280-284.
[5] 李维信,廖晓岗,唐宜,等. 镉对大鼠睾丸的损伤及锌保护作用的超微结构研究[J]. 解剖学报, 1988, 19(1):74-78
[6] 徐晨,李维信. 镉对大鼠精囊腺超微结构及 TPPase 细胞化学和血清睾酮含量的影响[J]. 解剖学报,1997,28(3):209-214
[7] 廖晓岗,李维信. 镉对大鼠附睾的损伤及锌保护作用的超微结构研究[J]. 解剖学报,1997,28(3):215-220
[8] 廖晓岗,李维信. 镉对大鼠睾丸间质细胞损伤及锌对其保护的形态学研究[J].生殖与避孕,1999,19(5):290-295
[9] 罗子国,李维信. 镉对大鼠输精管损伤及锌保护的超微结构与葡萄糖-6-磷酸酶细胞化学的研究[J]. 解剖学报,1999,30(1):86-89
[10]罗子国,李维信. 镉对大鼠前列腺损伤及锌保护的超微结构与硫胺素焦磷酸酶细胞化学的研究. 解剖学报,2000,31(4):366-371
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[2] 许舸,徐晨. 镉对中枢神经系统影响的研究进展[J]. 国外医学卫生学分册, 2005, 32(1):19-24
[3] Volchegorskii IA, Telesheva IB, Turygin VV. Age-related changes in cadmium content and oxidative modification of proteins in different regions of human spinal cord[J]. Bull Exp Biol Med, 2004, 137(5):440-442.
[4] Murphy VA, Embrey EC, Rosenberg JM, et al. Calcium deficiency enhances cadmium accumulation in the central nervous system[J]. Brain Res, 1991, 557(1-2):280-284.
[5] 李维信,廖晓岗,唐宜,等. 镉对大鼠睾丸的损伤及锌保护作用的超微结构研究[J]. 解剖学报, 1988, 19(1):74-78
[6] 徐晨,李维信. 镉对大鼠精囊腺超微结构及 TPPase 细胞化学和血清睾酮含量的影响[J]. 解剖学报,1997,28(3):209-214
[7] 廖晓岗,李维信. 镉对大鼠附睾的损伤及锌保护作用的超微结构研究[J]. 解剖学报,1997,28(3):215-220
[8] 廖晓岗,李维信. 镉对大鼠睾丸间质细胞损伤及锌对其保护的形态学研究[J].生殖与避孕,1999,19(5):290-295
[9] 罗子国,李维信. 镉对大鼠输精管损伤及锌保护的超微结构与葡萄糖-6-磷酸酶细胞化学的研究[J]. 解剖学报,1999,30(1):86-89
[10]罗子国,李维信. 镉对大鼠前列腺损伤及锌保护的超微结构与硫胺素焦磷酸酶细胞化学的研究. 解剖学报,2000,31(4):366-371
[11]Schroder HD. Organization of the motoneurons innervating the pelvic muscles of the male rat[J]. J Comp Neurol, 1980, 192(3):567-587.
[12]McKenna, K. E. and Nadelhaft I. The organization of the pudendal nerve in the male and female rat[J]. J Comp Neurol, 1986, 248(4): 532-549.
[13]Hodges LL, Jordan CL, Breedlove SM. Hormone-sensitive periods for the control of motoneuron number and soma size in the dorsolateral nucleus of the rat spinal cord[J]. Brain Res, 1993, 602(2):187-190.
[14]Nordeen EJ, Nordeen KW, Sengelaub DR, et al. Androgens prevent normally occurring cell death in a sexually dimorphic spinal nucleus[J]. Science, 1985, 229(4714): 671-673.
[15]Ward OB, Wexler AM, Carlucci JR, et al. Critical periods of sensitivity of sexually dimorphic spinal nuclei to prenatal testosterone exposure in female rats[J]. Horm Behav, 1996, 30(4):407-415.
[16]Goldstein LA, Sengelaub DR. Motoneuron morphology in the dorsolateral nucleus of the rat spinal cord: normal development and androgenic regulation[J]. J Comp Neurol, 1993, 338(4):588-600.
[17]Collins WF 3rd, Seymour AW, Klugewicz SW. Differential effect of castration on the somal size of pudendal motoneurons in the adult male rat[J]. Brain Res, 1992, 577(2):326-330.
[18]Breedlove SM, Arnold AP. Sexually dimorphic motor nucleus in the rat lumbar spinal cord: response to adult hormone manipulation, absence in androgen-insensitive rats[J]. Brain Res, 1981, 225(2):297-307.
[19]Burke KA, Widows MR, Sengelaub DR. Synergistic effects of testosterone metabolites on the development of motoneuron morphology in a sexually dimorphic rat spinal nucleus[J]. J Neurobiol, 1997, 33(1):1-10.
[20]Watson NV, Freeman LM, Breedlove SM. Neuronal size in the spinal nucleus of the bulbocavernosus: direct modulation by androgen in rats with mosaic androgen insensitivity[J]. J Neurosci, 2001, 21(3):1062-1066.
[21]Kurz EM, Brewer RG, Sengelaub DR. Hormonally mediated plasticity of motoneuron morphology in the adult rat spinal cord: a cholera toxin-HRP study[J]. J Neurobiol, 1991, 22(9):976-988.
[22]Kurz EM, Sengelaub DR, Arnold AP. Androgens regulate the dendritic length of mammalian motoneurons in adulthood[J]. Science, 1986, 232(4748):395-398.
[23]Leedy MG, Beattie MS, Bresnahan JC. Testosterone-induced plasticity of synaptic inputs to adult mammalian motoneurons[J]. Brain Res, 1987, 424(2):386-390.
[24]Matsumoto A, Micevych PE, Arnold AP. Androgen regulates synaptic input to motoneurons of the adult rat spinal cord[J]. J Neurosci, 1988, 8(11):4168-4176.
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