【摘要】：研究目的 OSAHS是以反復(fù)發(fā)生上氣道完全或部分阻塞導(dǎo)致呼吸暫�；虻屯�,其突出的病理生理過(guò)程是夜間反復(fù)發(fā)作性低氧/復(fù)氧。反復(fù)發(fā)作性低氧/復(fù)氧-即慢性間歇缺氧可以導(dǎo)致多器官損害,神經(jīng)系統(tǒng)損害尤其常見(jiàn),例如記憶力下降,認(rèn)知功能受損等。大量海馬組織神經(jīng)元凋亡是OSAHS患者學(xué)習(xí)和認(rèn)知功能損害的關(guān)鍵,活性氧在慢性間歇缺氧對(duì)海馬神經(jīng)元長(zhǎng)期損害中起關(guān)鍵作用。 持續(xù)氣道正壓通氣(CPAP)是目前治療OSAHS中療效最確切的一種方法,但仍有部分患者白天嗜睡改善不明顯,有部分患者不能耐受呼吸機(jī)而放棄治療,尤其是輕中度睡眠呼吸暫停患者順從性差。 慢性間歇缺氧是OSAHS患者最重要的病理生理特征,因此用OSAHS動(dòng)物模型探討慢性間歇缺氧對(duì)靶器官損害的機(jī)制及相應(yīng)的干預(yù)方法目前已成為臨床研究的熱點(diǎn)。為此,我們選用慢性間歇缺氧大鼠模型研究OSAHS患者存在的缺氧/再?gòu)?fù)氧病理生理過(guò)程,同時(shí)應(yīng)用抗氧化劑褪黑素進(jìn)行治療,觀察慢性間歇缺氧海馬組織中氧化應(yīng)激指標(biāo)MDA、SOD及bcl-2,bax蛋白的表達(dá)及海馬神經(jīng)元凋亡情況。探討抗氧化劑MT在CIH大鼠模型中的治療作用及其相關(guān)作用機(jī)制。 方法 將30只2月齡SD健康雄性大鼠隨機(jī)分為常氧+2%的乙生理鹽水腹腔注射對(duì)照組(A, n=10);慢性間歇缺氧+2%的醇理鹽水腹腔注射組(B, n=10);慢性間歇缺氧+2%的乙醇黑素腹腔注射組(C, n=10)。采用化學(xué)比色法檢測(cè)海馬組織化應(yīng)激指標(biāo)超:超氧化物歧化酶(SOD)、丙二醛(MDA)水平;用免疫組化學(xué)SP法檢測(cè)海馬組織凋亡指標(biāo):bax,bcl-2蛋白的表達(dá)水平;采用TUNEL法檢測(cè)海馬組織神經(jīng)元凋亡率。 結(jié)果 MT治療組海馬組織中MDA水平[(0.6760±0.0687)nmol/mg蛋白]顯著低于正常對(duì)照組[(1.1±0.16)nmol/mg蛋白]和CIH組[ (1.7±0.17)nmol/mg蛋白)],各組大鼠海馬組織中MDA水平,組間比較差異有統(tǒng)計(jì)學(xué)意(F=12.876,P0.01)。MT治療組大鼠海馬組織中SOD活性[(46.92±5.66)U/mg蛋白明顯高于CIH組([32.288±2.984)U/mg蛋白],但低于正常對(duì)照組[(64.28±5.29)U/mg蛋白],各組間比較均有統(tǒng)計(jì)學(xué)差異(F=11.2525,P0.01)。MT治療組的bcl-2蛋白的陽(yáng)性表達(dá)細(xì)胞灰度值(0.220±0.029)較CIH組(0.0968±0.0173)及正常組(0.142±0.0178)明顯增高F=64.138,P0.0差異有統(tǒng)計(jì)學(xué)意義。MT治療組組的bax蛋白的陽(yáng)性表達(dá)灰度值(0.135±0.00688)較CIH組(0.222±0.0256)及正常對(duì)照組降低(0.176±0.012),F=34.759,P0.05),差異有統(tǒng)計(jì)學(xué)意義。MT治療組的凋亡細(xì)胞陽(yáng)性表達(dá)細(xì)胞灰度值(0.1930±0.0202)較CIH組(0.335±0.0532)明顯降低,但較正常對(duì)照(0.0675±0.0125)高,(F=64.138 P0.05)差異有統(tǒng)計(jì)學(xué)意義 結(jié)論 褪黑素對(duì)慢性間歇缺氧大鼠海馬神經(jīng)元凋亡有明顯的抑制及抗氧化應(yīng)激作用,bcl-2表達(dá)降低和bax表達(dá)增加可能是其凋亡機(jī)制之一
[Abstract]:Objective OSAHS is caused by apnea or hypopnea caused by repeated complete or partial obstruction of upper airway. The prominent pathophysiological process of OSAHS is repeated paroxysmal hypoxia / reoxygenation at night. Recurrent hypoxic / reoxygenation-chronic intermittent hypoxia can lead to multiple organ damage, especially in the nervous system, such as memory loss, cognitive impairment and so on. A large number of hippocampal neurons apoptosis is the key to learning and cognitive impairment in patients with OSAHS. Reactive oxygen species (Ros) play a key role in the long-term damage of hippocampal neurons caused by chronic intermittent hypoxia. Continuous positive airway pressure ventilation (CPAP) is the most effective method in the treatment of OSAHS, but there are still some patients who are unable to tolerate ventilator and give up treatment. Especially mild to moderate sleep apnea patients with poor compliance. Chronic intermittent hypoxia is the most important pathophysiological feature in patients with OSAHS. Therefore, the mechanism of chronic intermittent hypoxia on target organ damage and the corresponding intervention methods have become the focus of clinical research. Therefore, we selected the chronic intermittent hypoxia rat model to study the pathophysiological process of hypoxia / reoxygenation in patients with OSAHS, and treated with antioxidant melatonin, and observed the oxidative stress index MDA, in the hippocampus of chronic intermittent hypoxia. Expression of SOD and bcl-2,bax protein and apoptosis of hippocampal neurons. To investigate the therapeutic effect of antioxidant MT in CIH rat model and its related mechanism. Methods Thirty 2-month-old SD healthy male rats were randomly divided into 2% normoxic saline group (A, n = 10), chronic intermittent hypoxia group (B, n = 10), chronic intermittent hypoxia group (B, n = 10) and chronic intermittent hypoxia group (n = 2). Chronic intermittent hypoxia 2% ethanol melanin intraperitoneal injection group (C 10). The levels of superoxide dismutase (SOD),) malondialdehyde (MDA) and apoptosis index (bax,bcl-2 protein) in hippocampus were detected by chemical colorimetry and immunohistochemistry (SP method) respectively. The apoptosis rate of hippocampal neurons was detected by TUNEL method. Results the level of MDA [(0.6760 鹵0.0687) nmol/mg protein] in hippocampus in MT group was significantly lower than that in normal control group [(1.1 鹵0.16) nmol/mg protein] and CIH group [(1.7 鹵0.17) nmol/mg protein]. The level of MDA in hippocampal tissue of rats in each group was significantly higher than that in the control group (F = 12.876, P < 0.05). The activity of SOD in hippocampus of P0.01). MT group [(46.92 鹵5.66) U/mg protein] was significantly higher than that of CIH group ([32.288 鹵2.984) U/mg protein], but lower than that of normal control group [(64.28 鹵5.29) U/mg protein]. There were statistical differences among the three groups (F = 11.2525, F = 11.2525). Compared with CIH group (0.0968 鹵0.0173) and normal group (0.142 鹵0.0178), the gray value of bcl-2 protein positive cells in P0.01). MT treatment group (0.220 鹵0.029) was significantly higher than that in CIH group (0.142 鹵0.0178). The expression of bax protein in MT group (0.135 鹵0.00688) was significantly lower than that in CIH group (0.222 鹵0.0256) and normal control group (0.176 鹵0.012). The gray value of apoptotic cells in MT group (0.1930 鹵0.0202) was significantly lower than that in CIH group (0.335 鹵0.0532), but higher than that in normal control group (0.0675 鹵0.0125). Conclusion melatonin has obvious inhibitory effect on apoptosis of hippocampal neurons in chronic intermittent hypoxia rats and antioxidant stress. The decrease of bcl-2 expression and the increase of bax expression may be one of the mechanisms of apoptosis.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R766.43

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相關(guān)期刊論文 前1條

1 劉輝國(guó);張志鋒;張珍祥;高永平;牛汝楫;;間歇缺氧大鼠海馬神經(jīng)元凋亡及其機(jī)制[J];中華結(jié)核和呼吸雜志;2007年05期

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本文編號(hào)：2319929