甲基苯丙胺对雄性大鼠睾酮水平的影响及相关机制研究

发布时间：2018-04-10 09:11

本文选题：甲基苯丙胺　切入点：睾酮　出处：《昆明医科大学》2017年硕士论文

【摘要】：[目的]探讨甲基苯丙胺对雄性大鼠睾酮水平的影响及相关机制。通过检测睾酮及相关激素水平,观察睾丸组织学的变化,分析睾丸内8-羟脱氧鸟苷表达的变化,为MA滥用对男性睾酮的水平影响及相关机制,提供科学的实验依据。[方法]雄性SD大鼠50只,体重230-250g,随机分成实验组(25只)和对照组(25只),实验组和对照组再分为3天、7天、14天、28天、56天组(每组5只)。采用MA(8m/kg)进行腹腔注射制作实验模型,3天、7天、14天、28天、56天时,腹主动脉放血处死大鼠,利用光镜观察大鼠睾丸生殖细胞形态结构变化,用化学发光法检测大鼠血清黄体生成素和卵泡刺激素以及血清和睾丸内睾酮水平,采用酶联免疫吸附法(ELISA)测定睾丸内8-羟脱氧鸟苷含量。[结果](1)MA组大鼠的睾丸生精上皮层次减少,仅有2-4层,细胞排列疏松,部分排列紊乱,间质水肿,部分精原细胞脱落、精母细胞可见核内空泡化和水肿,个别精细胞坏死现象。(2)与对照组相比,甲基苯丙胺给药后3天,血清中LH出现升高,但无显著性差异(p0.05),随后LH水平出现逐渐下降趋势,14天时下降有统计学差异(p0.05),并随着MA注射时间的延长而明显降低(28天、56天p0.01)。与对照组相比,甲基苯丙胺给药初期(3天、7天)血清FSH无明显改变(p0.05),随后FSH水平逐渐降低(p0.05或p0.01)。(3)睾丸中8-OHdG水平随着MA给药时间延长而逐渐升高,14天时有统计学差异(p0.05)。(4)MA给药后3天,MA给药组血清睾酮较对照组略有升高,随后睾酮水平逐渐下降,28天和56天MA给药组与对照组相比有统计学意义(p0.05,p0.01),3天时睾丸匀浆内睾酮也出现升高,但无显著性差异(p0.05),随后睾酮水平出现下降趋势,其中睾丸匀浆14天时较血清睾酮率先在统计学上出现下降(p0.05)。[结论]1、MA可以引起雄性大鼠生殖细胞病理损伤。2、MA使睾丸内DNA氧化损伤增加,长期使用MA可能是导致DNA氧化损伤的因素,并且呈时间依赖,造成雄性大鼠睾丸组织损害。3、MA还可以下调性腺轴上位激素LH、FHS,使大鼠的血清睾酮及睾丸内睾酮水平下降。以上结论表明,腹腔注射MA使大鼠睾酮分泌下降,其机制为通过下调雄性大鼠LH、FHS,增加睾丸内的氧化应激,在两者共同作用下使雄性大鼠睾酮的分泌受到抑制。
[Abstract]:[objective] to investigate the effect of methamphetamine on testosterone level in male rats and its related mechanism.By detecting testosterone and related hormones, observing the changes of testis histology and analyzing the changes of 8-hydroxydeoxyguanosine (8-hydroxydeoxyguanosine) expression in testis, this paper provides a scientific experimental basis for the effect of MA abuse on male testosterone level and its related mechanism.[methods] 50 male Sprague-Dawley rats weighing 230-250 g were randomly divided into two groups: the experimental group (n = 25) and the control group (n = 25). The experimental group and the control group were further divided into 3 days, 7 days, 14 days, 28 days and 56 days group (5 rats in each group).The experimental model was made by intraperitoneal injection with 8 m / kg MAG. The rats were sacrificed by abdominal aorta bloodletting for 3 days, 14 days and 28 days and 56 days. The morphological and structural changes of germ cells in testis were observed by light microscope.The levels of luteinizing hormone and follicle stimulating hormone in serum and testosterone in serum and testis of rats were detected by chemiluminescence assay and 8-hydroxydeoxyguanosine in testis was determined by enzyme linked immunosorbent assay (Elisa).[results] the levels of testicular spermatogenic epithelium in the MA group decreased, with only 2-4 layers. The cells were loosely arranged, partially disordered, interstitial edema, some spermatogonium cells fell off, and vacuolation and edema were observed in the nucleus of spermatocytes.Compared with the control group, serum LH level increased 3 days after methamphetamine administration.However, there was no significant difference in the level of LH between the two groups. The level of LH decreased gradually at the 14th day, and decreased significantly with the prolongation of the time of MA injection, and decreased significantly at the end of 28 days and 56 days after the injection of MA (P 0.01).Compared with the control group,Compared with the control group, the serum testosterone of the group treated with TMA was slightly higher than that of the control group.The testosterone levels in the testis homogenate of the MA group were significantly higher than those of the control group on the 28th and 56th day after treatment, but there was no significant difference in testosterone level between the two groups, but there was no significant difference in the testosterone level between the two groups, and then the level of testosterone decreased, and the level of testosterone in the testis homogenate increased at the 3rd day after the treatment, but there was no significant difference in the testosterone level between the two groups.The testicular homogenate at 14 days was the first to show a statistical decrease in serum testosterone (p 0.05).[conclusion] (1) DNA oxidative damage in testis of male rats was increased by MA. The long-term use of MA may be the cause of DNA oxidative damage in a time dependent manner.The damage of testicular tissue in male rats. 3MA can also down-regulate the upper gonadal axis hormone (LHH) FHSs, and decrease the levels of serum testosterone and testosterone in testis of male rats.These results suggest that intraperitoneal injection of MA can decrease testosterone secretion in male rats through down-regulation of LHH FHSs and increase oxidative stress in testis, and inhibit testosterone secretion in male rats under the combined action of both.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.64

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