本文選題：胰島素 + 凋亡��； 參考：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:代謝綜合征已成為世界范圍內(nèi)的健康問題。以高血糖、肥胖、高血壓和胰島素抵抗為特征的代謝綜合征及其合并癥,對(duì)人群健康構(gòu)成嚴(yán)重威脅。胰島素抵抗及其相關(guān)的代謝綜合征,與育齡期女性的生殖問題密切相關(guān)。子宮內(nèi)膜蛻膜化對(duì)維持胚胎的正常發(fā)育具有重要作用。子宮內(nèi)膜蛻膜化的異常可導(dǎo)致胚胎無法正常獲取營養(yǎng),從而致胚胎不能正常發(fā)育。課題組在前期研究中已經(jīng)證實(shí)高水平胰島素對(duì)早孕小鼠子宮內(nèi)膜蛻膜化有影響,但其機(jī)制尚不明確。卵巢分泌的雌激素和孕酮對(duì)子宮內(nèi)膜蛻膜化至關(guān)重要。有研究已經(jīng)證實(shí)胰島素可通過一系列信號(hào)通路調(diào)節(jié)細(xì)胞凋亡,且卵巢細(xì)胞的凋亡平衡是蛻膜化正常進(jìn)行的重要保證。因此,本文旨在研究高水平胰島素對(duì)妊娠早期卵巢細(xì)胞凋亡的影響,并進(jìn)一步探討其可能的機(jī)制。方法:1.動(dòng)物模型的建立及標(biāo)本收集:購買8周齡昆明鼠飼養(yǎng),分別建立正常組和高胰島素小鼠模型。將正常(或結(jié)扎輸精管)雄鼠與雌鼠進(jìn)行交配,次日見陰栓標(biāo)記為D1(或PD1),分別收集正常組與高胰島素組D7、D8(或PD7、PD8)的血清和卵巢組織。2.高胰島素對(duì)早孕小鼠卵巢凋亡的影響:(1)TUNEL方法檢測早孕小鼠D8卵巢細(xì)胞的調(diào)亡;(2)免疫組化檢測孕D8小鼠卵巢Bax和Bcl2的表達(dá);(3)westernblot檢測正常妊娠(d7,d8)以及假孕(pd7,pd8)小鼠卵巢凋亡相關(guān)蛋白的表達(dá)。3.高濃度胰島素對(duì)早孕小鼠卵巢pi3k/akt信號(hào)通路相關(guān)蛋白的影響:(1)westernblot檢測正常妊娠(d7,d8)以及假孕(pd7,pd8)小鼠卵巢pi3k/akt信號(hào)通路相關(guān)蛋白的表達(dá);(2)宮角注射pi3k/akt信號(hào)通路特異抑制劑ly294002,進(jìn)一步分析pi3k/akt信號(hào)通路是否參與高濃度胰島素對(duì)早孕小鼠卵巢細(xì)胞凋亡的影響。結(jié)果:1.高濃度胰島素對(duì)早孕小鼠激素分泌的影響:elisa結(jié)果顯示高胰島素組小鼠d7和d8天血清中胰島素濃度顯著升高,而e2、p4濃度均顯著降低。2.高濃度胰島素對(duì)早孕小鼠卵巢凋亡的影響:tunel結(jié)果顯示高胰島素組早孕小鼠卵巢細(xì)胞凋亡顯著降低;免疫組化結(jié)果顯示高胰島素組早孕小鼠卵巢組織bax表達(dá)顯著下降而bcl2表達(dá)顯著升高;westernblot結(jié)果顯示高胰島素組早孕小鼠卵巢組織bax、cleaved-casepase3、cleaved-parp表達(dá)明顯降低而bcl2表達(dá)明顯升高。3.pi3k/akt信號(hào)通路參與高胰島素抑制的早孕小鼠卵巢細(xì)胞凋亡:westernblot結(jié)果顯示akt磷酸化在高胰島素組早孕小鼠卵巢組織中被激活。抑制劑ly294002能夠改善高水平胰島素引起的卵巢凋亡以及pi3k/akt信號(hào)通路相關(guān)蛋白的表達(dá)。結(jié)論:高胰島素可能抑制早孕小鼠卵巢組織的凋亡,pi3k/akt信號(hào)通路可能參與這一過程,但其具體機(jī)制還有待進(jìn)一步研究。
[Abstract]:Objective: metabolic syndrome has become a worldwide health problem. Metabolic syndrome and its complication, characterized by hyperglycemia, obesity, hypertension and insulin resistance, constitute a serious threat to the health of the population. Insulin resistance and its associated metabolic syndrome are closely related to reproductive problems in women of childbearing age. Endometrial deciduization The abnormal decidua of the endometrium can lead to the failure of the embryo to get the normal nutrition, so that the embryo can not develop normally. In the previous study, the research group has confirmed that the high level insulin has a shadow on the endometriosis of the endometrium in the early pregnancy mice, but the mechanism is not clear. The ovary secreted by the ovary is not clear. Hormone and progesterone are essential for endometrial decidualization. Studies have shown that insulin can regulate apoptosis through a series of signaling pathways, and the apoptosis balance of ovarian cells is an important guarantee for normal decidualization. Therefore, this article aims to study the effect of high level of insulin on the apoptosis of ovarian cells in early pregnancy and to further study the effect of high level insulin on the early ovarian cell apoptosis. To explore the possible mechanism. Methods: 1. animal model establishment and specimen collection: 8 weeks old Kunming mice were bought to establish normal group and high insulin mouse model. Normal (or ligated vasa) male rats were copulated with female rats. The second day was D1 (or PD1), and the normal group and the high insulin group were collected, D7, D8 (or PD7, PD8), respectively. The effect of.2. hyperinsulinemia in serum and ovarian tissue on ovarian apoptosis in early pregnancy mice: (1) TUNEL method was used to detect the apoptosis of D8 ovarian cells in early pregnant mice; (2) immunohistochemistry was used to detect the expression of Bax and Bcl2 in the ovary of pregnant D8 mice; (3) Westernblot detection of normal pregnancy (D7, D8) and the expression of apoptosis related proteins in the ovary of mice (pd7, pd8) were highly concentrated The effect of insulin on the pi3k/akt signaling pathway related proteins in the ovary of early pregnancy mice: (1) Westernblot detection of normal pregnancy (D7, D8) and the expression of pi3k/akt signal pathway related proteins in the ovary of mice (pd7, pd8); (2) a specific inhibitor of pi3k/akt signaling in the uterine horn, LY294002, to further analyze the involvement of pi3k/akt signaling pathway. Effect of insulin concentration on the apoptosis of ovarian cells in early pregnancy mice. Results: 1. the effect of high insulin on the hormone secretion in early pregnancy mice: ELISA results showed that the serum insulin concentration in D7 and D8 days in high insulin group increased significantly, while E2, P4 concentration significantly reduced the effect of.2. high concentration insulin on premature ovarian apoptosis in mice: tunel The results showed that the apoptosis of ovarian cells in the early pregnancy mice was significantly lower than that in the high insulin group, and the immunohistochemical results showed that the expression of Bax in the ovarian tissue of the early pregnant mice was significantly decreased while the expression of BCL2 in the early pregnancy mice increased significantly, and the results of Westernblot showed that the expression of Bax, cleaved-casepase3 and cleaved-parp in the early pregnancy mice of the hyperinsulinic group was significantly reduced by BC. L2 expression significantly increased.3.pi3k/akt signaling pathway involved in the apoptosis of ovarian cells in early pregnancy mice with high insulin inhibition. Westernblot results showed that Akt phosphorylation was activated in the ovarian tissue of early pregnant mice with high insulin. Inhibitor LY294002 could improve the ovarian apoptosis induced by high level insulin and pi3k/akt signaling pathway related proteins. Conclusion: high insulin may inhibit the apoptosis of ovarian tissue in early pregnancy mice. Pi3k/akt signaling pathway may be involved in this process, but its specific mechanism remains to be further studied.

【學(xué)位授予單位】：重慶醫(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)】：R714

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