本文選題：慢性不可預(yù)見性應(yīng)激 + 抑郁癥��； 參考：《新鄉(xiāng)醫(yī)學院》2012年碩士論文

【摘要】：目的 1、建立慢性不可預(yù)見性應(yīng)激(CUS)抑郁模型。 2、檢測抑郁模型大鼠海馬促分裂原活化蛋白激酶磷酸酶-1(MKP-1)表達及啟動子區(qū)DNA甲基化狀態(tài)的變化情況。 3、探討抗抑郁藥對抑郁模型大鼠海馬MKP-1表達及啟動子區(qū)DNA甲基化狀態(tài)的影響。 方法 1、動物分組及模型制作選擇曠場實驗得分相近的30只SD大鼠隨機分為3組,正常對照組(A組)10只,生理鹽水組(B組)10只,氟西汀組(C組)10只。慢性不可預(yù)見性應(yīng)激共實施42天,每天給予不同的不可預(yù)見性應(yīng)激,一種應(yīng)激在一周內(nèi)最多使用2次。用曠場實驗和體質(zhì)量來評價抑郁模型。 2、采用逆轉(zhuǎn)錄聚合酶鏈反應(yīng)(RT-PCR)方法檢測抑郁模型大鼠海馬MKP-1mRNA的表達情況。 3、采用聯(lián)合NaHSO3限制性酶切分析法(COBRA)檢測MKP-1基因啟動子區(qū)DNA甲基化情況。 4、采用統(tǒng)計軟件SPSS12.0處理,數(shù)據(jù)以均數(shù)±標準差(x±s)表示,組間比較采用單因素方差分析(ANOVA)。以P0.05為差異有統(tǒng)計學意義。 結(jié)果 1、曠場試驗 (1)水平運動：刺激之前,各組大鼠在水平運動方面差異無統(tǒng)計學意義(P=0.457)。慢性刺激21天后,生理鹽水組的水平運動距離遠于正常對照組(P=0.005),而生理鹽水組與氟西汀組比較差異無統(tǒng)計學意義(P=0.128),正常對照組與氟西汀組比較差異無統(tǒng)計學意義(P=0.148)。藥物干預(yù)21天后,生理鹽水組的水平運動距離比正常對照組水平運動距離縮短(P=0.000),但氟西汀組水平運動距離較生理鹽水組延長(P=0.000),正常對照組和氟西汀組的差異無統(tǒng)計學意義(P=0.393)。(2)垂直運動：在垂直運動方面,刺激之前,刺激21天及干預(yù)21天時3個時間點正常對照組、生理鹽水組與氟西汀組比較差異均無統(tǒng)計學意義(P=0.260,0.960,0.697)。 2、體質(zhì)量：刺激之前,各組比較差異無統(tǒng)計學意義(P=0.476)。慢性刺激21天時,生理鹽水組體質(zhì)量較正常對照組的體質(zhì)量減輕(P=0.010),氟西汀組的體質(zhì)量也較正常對照組的體質(zhì)量減輕(P=0.000),生理鹽水組體質(zhì)量與氟西汀組體質(zhì)量比較差異無統(tǒng)計學意義(P=0.109)。干預(yù)21天時,生理鹽水組體質(zhì)量較正常對照組的體質(zhì)量減輕(P=0.000),氟西汀組的體質(zhì)量也較正常對照組的體質(zhì)量減輕(PP=0.000),氟西汀組體質(zhì)量較生理鹽水組體質(zhì)量增加(P=0.026)。 3、生理鹽水組MKP-1mRNA的表達較正常對照組升高(P=0.001),較氟西汀組MKP-1mRNA的表達也升高(P=0.024)；但氟西汀組MKP-1mRNA的表達與正常對照組比較差異無統(tǒng)計學意義(P=0.097)。 4、MKP-1基因啟動子區(qū)DNA甲基化的檢測未檢測到MKP-1基因啟動子區(qū)存在DNA甲基化。 結(jié)論 1、CUS抑郁模型大鼠海馬MKP-1mRNA表達水平較正常對照組升高,MKP-1可能參與了抑郁癥的發(fā)病機制。 2、氟西汀可以明顯改善抑郁模型大鼠的抑郁行為,并能改善海馬MKP-1mRNA的高表達,提示氟西汀可能通過調(diào)節(jié)MKP-1mRNA表達參與抗抑郁劑的治療機制。 3、CUS抑郁模型大鼠海馬MKP-1基因的啟動子區(qū)未發(fā)現(xiàn)存在DNA甲基化,提示MKP-1基因啟動子區(qū)的DNA甲基化可能不參與抑郁癥的發(fā)病機制。
[Abstract]:objective
1, establish a chronic unpredictable stress (CUS) depression model.
2, we detected the expression of mitogen activated protein kinase phosphatase -1 (MKP-1) and DNA methylation status in hippocampus of depression model rats.
3, to explore the effect of antidepressants on MKP-1 expression and DNA methylation status in hippocampus of depression model rats.
Method
1, 30 SD rats were randomly divided into 3 groups, including 10 rats in the normal control group, 10 in the normal control group, 10 in the saline group (group B) and 10 in the fluoxetine group (group C). The chronic unpredictable stress was carried out for 42 days, and the different unpredictable stress was given every day. A kind of stress was used up to 2 times in a week. Depressive model was evaluated by open field experiment and body mass.
2, reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of MKP-1mRNA in hippocampus of depression model rats.
3, combined NaHSO3 restriction enzyme digestion assay (COBRA) was used to detect the DNA methylation status of MKP-1 gene promoter region.
4, the data were treated with statistical software SPSS12.0, and the data were expressed with mean standard deviation (x + s), and the single factor variance analysis (ANOVA) was used in the group. The difference was statistically significant with the difference of P0.05.
Result
1, open field test
(1) horizontal exercise: before stimulation, there was no significant difference in horizontal movement between the rats in each group (P=0.457). 21 days after the chronic stimulation, the horizontal movement distance of the saline group was far higher than that of the normal control group (P=0.005), while the difference of the normal saline group and the fluoxetine group had no statistical significance (P=0.128), and the normal control group was less than the fluoxetine group. There was no statistical significance (P=0.148). The horizontal movement distance of the normal saline group was shorter than that of the normal control group (P=0.000) after 21 days of drug intervention, but the horizontal movement distance of the fluoxetine group was longer than that of the normal saline group (P=0.000), and there was no significant difference between the normal control group and the fluoxetine group (P=0.393). (2) the vertical movement was in drooping. There was no significant difference between the normal saline group and the fluoxetine group before the stimulation, the stimulation for 21 days and the 3 time points of the intervention for 21 days, and there was no significant difference between the normal saline group and the fluoxetine group (P=0.260,0.960,0.697).
2, body mass: before stimulation, there was no significant difference between each group (P=0.476). At 21 days of chronic stimulation, the mass of the saline group was less than that of the normal control group (P=0.010), and the body mass of the fluoxetine group was also less than that of the normal control group (P=0.000), and the quality of the saline group was compared with the quality of the fluoxetine group. There was no statistical significance (P=0.109). The body mass of the saline group was less than that of the normal control group (P=0.000) at 21 days, and the body mass of the fluoxetine group was also less than that of the normal control group (PP=0.000), and the mass of the fluoxetine group was higher than that of the saline group (P=0.026).
3, the expression of MKP-1mRNA in the normal saline group was higher than that in the normal control group (P=0.001), and the expression of MKP-1mRNA in the fluoxetine group increased (P=0.024), but the expression of MKP-1mRNA in the fluoxetine group was not significantly different from that of the normal control group (P=0.097).
4, detection of DNA methylation in the promoter region of MKP-1 gene did not detect DNA methylation in the promoter region of MKP-1 gene.
conclusion
1, the expression level of MKP-1mRNA in hippocampus of CUS depression model rats is higher than that of normal control group. MKP-1 may be involved in the pathogenesis of depression.
2, fluoxetine can obviously improve the depressive behavior of the depression model rats and improve the high expression of MKP-1mRNA in the hippocampus, suggesting that fluoxetine may be involved in the treatment mechanism of antidepressant by regulating the expression of MKP-1mRNA.
3, DNA methylation was not found in the promoter region of MKP-1 gene in the CUS depression model rats, suggesting that DNA methylation in the promoter region of the MKP-1 gene may not be involved in the pathogenesis of depression.
【學位授予單位】：新鄉(xiāng)醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R749.4

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相關(guān)期刊論文 前1條

1 王長虹;謝春朋;李晏;千新來;師天元;;慢性應(yīng)激抑郁模型大鼠血清腦源性神經(jīng)營養(yǎng)因子水平的研究[J];新鄉(xiāng)醫(yī)學院學報;2010年05期

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本文編號：2066097