本文選題：甲基苯丙胺　切入點(diǎn)：睪酮　出處：《昆明醫(yī)科大學(xué)》2017年碩士論文

【摘要】：[目的]探討甲基苯丙胺對(duì)雄性大鼠睪酮水平的影響及相關(guān)機(jī)制。通過(guò)檢測(cè)睪酮及相關(guān)激素水平,觀察睪丸組織學(xué)的變化,分析睪丸內(nèi)8-羥脫氧鳥(niǎo)苷表達(dá)的變化,為MA濫用對(duì)男性睪酮的水平影響及相關(guān)機(jī)制,提供科學(xué)的實(shí)驗(yàn)依據(jù)。[方法]雄性SD大鼠50只,體重230-250g,隨機(jī)分成實(shí)驗(yàn)組(25只)和對(duì)照組(25只),實(shí)驗(yàn)組和對(duì)照組再分為3天、7天、14天、28天、56天組(每組5只)。采用MA(8m/kg)進(jìn)行腹腔注射制作實(shí)驗(yàn)?zāi)Ｐ?3天、7天、14天、28天、56天時(shí),腹主動(dòng)脈放血處死大鼠,利用光鏡觀察大鼠睪丸生殖細(xì)胞形態(tài)結(jié)構(gòu)變化,用化學(xué)發(fā)光法檢測(cè)大鼠血清黃體生成素和卵泡刺激素以及血清和睪丸內(nèi)睪酮水平,采用酶聯(lián)免疫吸附法(ELISA)測(cè)定睪丸內(nèi)8-羥脫氧鳥(niǎo)苷含量。[結(jié)果](1)MA組大鼠的睪丸生精上皮層次減少,僅有2-4層,細(xì)胞排列疏松,部分排列紊亂,間質(zhì)水腫,部分精原細(xì)胞脫落、精母細(xì)胞可見(jiàn)核內(nèi)空泡化和水腫,個(gè)別精細(xì)胞壞死現(xiàn)象。(2)與對(duì)照組相比,甲基苯丙胺給藥后3天,血清中LH出現(xiàn)升高,但無(wú)顯著性差異(p0.05),隨后LH水平出現(xiàn)逐漸下降趨勢(shì),14天時(shí)下降有統(tǒng)計(jì)學(xué)差異(p0.05),并隨著MA注射時(shí)間的延長(zhǎng)而明顯降低(28天、56天p0.01)。與對(duì)照組相比,甲基苯丙胺給藥初期(3天、7天)血清FSH無(wú)明顯改變(p0.05),隨后FSH水平逐漸降低(p0.05或p0.01)。(3)睪丸中8-OHdG水平隨著MA給藥時(shí)間延長(zhǎng)而逐漸升高,14天時(shí)有統(tǒng)計(jì)學(xué)差異(p0.05)。(4)MA給藥后3天,MA給藥組血清睪酮較對(duì)照組略有升高,隨后睪酮水平逐漸下降,28天和56天MA給藥組與對(duì)照組相比有統(tǒng)計(jì)學(xué)意義(p0.05,p0.01),3天時(shí)睪丸勻漿內(nèi)睪酮也出現(xiàn)升高,但無(wú)顯著性差異(p0.05),隨后睪酮水平出現(xiàn)下降趨勢(shì),其中睪丸勻漿14天時(shí)較血清睪酮率先在統(tǒng)計(jì)學(xué)上出現(xiàn)下降(p0.05)。[結(jié)論]1、MA可以引起雄性大鼠生殖細(xì)胞病理?yè)p傷。2、MA使睪丸內(nèi)DNA氧化損傷增加,長(zhǎng)期使用MA可能是導(dǎo)致DNA氧化損傷的因素,并且呈時(shí)間依賴,造成雄性大鼠睪丸組織損害。3、MA還可以下調(diào)性腺軸上位激素LH、FHS,使大鼠的血清睪酮及睪丸內(nèi)睪酮水平下降。以上結(jié)論表明,腹腔注射MA使大鼠睪酮分泌下降,其機(jī)制為通過(guò)下調(diào)雄性大鼠LH、FHS,增加睪丸內(nèi)的氧化應(yīng)激,在兩者共同作用下使雄性大鼠睪酮的分泌受到抑制。
[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.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R749.64

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