本文關(guān)鍵詞： 地佐辛 嗎啡 睪酮 黃體生成素 卵泡刺激素　出處：《南華大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的： 探討地佐辛(dezocine)長時程應(yīng)用對雄性小鼠生育能力的影響;初步探討地佐辛(dezocine)長時程應(yīng)用導(dǎo)致雄性小鼠生殖功能損害的可能機制。 方法： 實驗選用6周齡C57雄性小鼠60只，體重18~20g，隨機分為5組，每組12只，分別為陰性對照組(對照組)，陽性對照組嗎啡組(M組)，地佐辛D1(15mg/kg)、D2(20mg/kg)、D3(25mg/kg)組。小鼠適應(yīng)性飼養(yǎng)1周后開始腹腔注射給藥。實驗過程中，每天給藥之后即刻及用藥6小時后觀察小鼠一般情況；于實驗第21天停止給藥，，眼球取血，全自動生化分析儀檢測血T、LH及FSH水平；取睪丸組織常規(guī)石蠟組織切片，HE染色觀察小鼠睪丸病理形態(tài)學(xué)改變，免疫組織化學(xué)染色觀察促凋亡因子Bax及凋亡抑制因子Bcl-2在睪丸組織中的表達變化。 結(jié)果： 1.對照組小鼠腹腔注射后行為正常，其他各組小鼠腹腔注射后均出現(xiàn)興奮性行為改變，表現(xiàn)為豎尾、奔跑、爬籠等。注射6小時后再觀察，各組小鼠行為學(xué)表現(xiàn)均恢復(fù)正常。 2.HE染色結(jié)果顯示，對照組睪丸生精小管結(jié)構(gòu)完整、上皮細胞排列整齊，細胞層次清晰，各級生精細胞形態(tài)正常，可見大量成熟精子；M組睪丸組織基底膜不完整、生精小管層次紊亂、生精細胞層減少。D組睪丸組織基底膜破壞；生精細胞層排列紊亂、層數(shù)減少、細胞脫落、以精原細胞為主，可見精原細胞空泡變性；各級精母細胞減少、變性；精子畸形。隨著地佐辛劑量的增加，生精小管受損更為嚴(yán)重，地佐辛對于小鼠生精小管結(jié)構(gòu)的破壞存在劑量依賴性。 3.睪丸組織Bax的表達變化：M組，D1、D2、D3組均明顯高于對照組(p＜0.05),D3組與M組相比，Bax的表達顯著增加，差異有統(tǒng)計學(xué)意義(p＜0.05)；睪丸組織Bcl-2的表達變化：各用藥組明顯低于對照組(p＜0.05)；D1、D2、D3組間差異有顯著性(p＜0.05)，呈現(xiàn)劑量依賴性的表達降低； Bcl-2在D3組的表達顯著低于在M組的表達(p＜0.05),差異有統(tǒng)計學(xué)意義。 4.D3組小鼠血清卵泡刺激素(FSH)、睪酮(T)、黃體生成素(LH)的表達均低于對照組，差別有統(tǒng)計學(xué)意義(p＜0.05)；D3組FSH、T、LH的表達與M組相比，差異有顯著性(p0.05)。 結(jié)論： 地佐辛可以導(dǎo)致小鼠出現(xiàn)興奮表現(xiàn)，對小鼠睪丸組織結(jié)構(gòu)造成破壞，導(dǎo)致Bax和Bcl-2蛋白表達失衡，影響小鼠生殖功能。因此，在臨床應(yīng)用中應(yīng)該引起廣泛關(guān)注。
[Abstract]:Objective: To investigate the effect of long-term application of dizocine on the fertility of male mice. To explore the possible mechanism of reproductive dysfunction in male mice induced by long term application of dizocine. Methods: Sixty 6-week-old C57 male mice were randomly divided into 5 groups with 12 rats in each group (control group, morphine group, M group). The mice were given intraperitoneal injection of dizosin D _ (1) / kg ~ (15 mg / kg) ~ (20 mg 路kg ~ (-1) 路kg ~ (-1)) ~ (25 mg / kg)) after adaptive feeding for one week. The general situation of mice was observed immediately after administration every day and 6 hours after administration. On the 21st day of the experiment, the administration was stopped, blood was taken from the eyeball, and the levels of TLH and FSH in blood were detected by automatic biochemical analyzer. The pathological changes of testis in mice were observed by HE staining. Immunohistochemical staining was used to observe the expression of apoptosis-promoting factor Bax and apoptosis-inhibiting factor Bcl-2 in testis. Results: 1. The behavior of mice in the control group was normal after intraperitoneal injection, and the excitatory behavior of other mice was changed after intraperitoneal injection, showing as vertical tail, running, crawling cage and so on. After 6 hours of injection, the changes of excitatory behavior were observed. The behavior of each group of mice returned to normal. 2. The results of HE staining showed that the structure of testicular seminiferous tubules in the control group was intact, the epithelial cells were arranged neatly, the layers of cells were clear, the morphology of spermatogenic cells was normal, and a large number of mature sperm were observed. In group M, the basement membrane of testis was incomplete, the layer of seminiferous tubules was disordered, and the layer of spermatogenic cells was decreased. The layers of spermatogenic cells were disordered, the number of layers decreased, the cells fell off, mainly spermatogonium cells, the vacuolar degeneration of spermatogonium cells was observed. Reduction and degeneration of spermatocytes at all levels; Sperm malformation. With the increase of dizosin dose, the damage of seminiferous tubules was more serious, and the destruction of seminiferous tubules in mice was in a dose-dependent manner. 3. The expression of Bax in testis was significantly higher in group D 1 and D 2 D 3 than that in control group P < 0 05 and group D 3 compared with that in group M, and the expression of Bax in group D 1 and D 2 D 3 was significantly higher than that in group M (P < 0 05). The difference was statistically significant (P < 0.05). The changes of Bcl-2 expression in testicular tissue: the expression of Bcl-2 in each treatment group was significantly lower than that in the control group (P < 0.05); There was a significant difference between the two groups (P < 0.05), and the expression was decreased in a dose-dependent manner. The expression of Bcl-2 in group D 3 was significantly lower than that in group M (P < 0.05). 4. The expression of FSH, TX and LH in D3 group was lower than that in control group (P < 0.05). There was a significant difference in the expression of FSHT LH between group D 3 and group M (P 0.05). Conclusion: Dizosin can cause excitatory performance in mice, damage the structure of mouse testis, lead to the imbalance of Bax and Bcl-2 protein expression, and affect the reproductive function of mice. It should be paid more attention to in clinical application.
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R965

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