本文選題：阻塞性睡眠呼吸暫停低通氣綜合征 + 慢性間歇性低氧�。� 參考：《蘭州大學》2017年碩士論文

【摘要】：目的探討阻塞性睡眠呼吸暫停低通氣綜合征(OSAHS)在普通飲食、高脂飲食條件下引起腎臟損傷的機制以及復氧后腎臟組織結構以及腎臟功能的恢復。本研究是以慢性間歇性低氧(CIH)、高脂飲食模擬OSHAS及高脂飲食,其通過激活內質網(wǎng)應激反應(ERS)介導大鼠腎臟的損傷;并以復氧模擬臨床持續(xù)氣道內正壓通氣(CPAP)治療,觀察腎臟組織結構及功能的恢復。為臨床的治療提供新的診療思路。方法將48只SPF級健康的雄性Wistar大鼠,隨機分為4組,每組12只:A組:對照組(常氧及普通飲食組)、B組:高脂組(常氧及高脂飲食組)、C組:CIH組(CIH及普通飲食組)、D組:CIH合并高脂飲食組(CIH及高脂飲食組)。6周后每組隨機選取6只,檢測血清中胱抑素C(Cys-C)、高密度脂蛋白(HDL)、并行腎臟的CHOP蛋白免疫組化,并蘇木精-伊紅(HE)染色后在顯微鏡下觀察腎臟病理結構變化,以及電鏡下觀察腎小球及腎小管超微結構變化。再在原飲食條件下復氧2周,再次重復上述檢測,并進行比較。結果B組、C組、D組中腎早損指標Cys-C水平較A組顯著升高,且在D組中值最高(均P0.05);B組、D組中血脂指標HDL水平較A組顯著下降(均P0.05),C組與A組比較有下降,但無顯著差異(P0.05);B組、C組、D組中ERS標志性蛋白CHOP平均光密度值與A組比較顯著升高,且在D組中值最高(均P0.05)。HE染色光鏡下觀察發(fā)現(xiàn):A組腎臟組織未見明顯異常,在B組、C組中腎小球未見明顯異常,腎小管上皮細胞小部分水腫,D腎小球未見明顯異常,組腎小管上皮細胞大部分水腫;電鏡下觀察,B組、C組近曲腎小管上皮細胞局灶性核固縮,刷狀緣稀疏并脫落,D組中有大片腎小管上皮細胞核固縮,刷狀緣稀疏并脫落。并復氧2周后Cys-C水平在A組、B組與復氧前比較無顯著變化(均P0.05),在C組、D組中與復氧前比較顯著降低(均P0.05);復氧后HDL水平在A組、B組與復氧前比較有下降,但無顯著性差異(均P0.05),在C組與復氧前比較顯著升高(P0.05),在D組有升高,但無顯著性差異(P0.05)。復氧后CHOP蛋白平均光密度水平在腎臟中的表達,A組、B組水平與復氧前無明顯差異(均P0.05),C組、D組水平與復氧前比較明顯降低(均P0.05)。光鏡及電鏡下觀察:A組未見明顯異常,B組與復氧前比較水腫稍有加重,復氧前C組、D組與復氧后比較腎臟組織改善。結論1.CIH合并高脂飲食的模型建立。2.CIH、高脂可通過激活ERS介導近曲腎小管上皮的凋亡,使腎臟的超微結構發(fā)生改變,進而腎臟功能損傷。3.復氧可通過改善ERS,使腎臟結構與腎功能改善。
[Abstract]:Objective to investigate the mechanism of renal injury induced by obstructive sleep apnea hypopnea syndrome (OSAHS) under general diet and high fat diet, and to investigate the recovery of renal structure and function after reoxygenation. In this study, chronic intermittent hypoxia (CIH), high-fat diet, OSHAS and high-fat diet were used to induce renal injury in rats by activating endoplasmic reticulum stress response (ERS), and reoxygenation was used to simulate clinical continuous positive airway pressure ventilation (CPAP). To observe the recovery of renal tissue structure and function. To provide a new way of diagnosis and treatment for clinical treatment. Methods 48 SPF healthy male Wistar rats were randomly divided into 4 groups. 12 rats in each group: control group (normoxic group and normal diet group) group B: high fat group (normoxic and high fat diet group) and C group (CIH and general diet group), group D: CIH combined with high-fat diet group (CIH and high-fat diet group) 6 weeks after 6 weeks, 6 rats in each group were randomly selected. Cystatin C (Cys-C), high density lipoprotein (HDL), chop protein immunohistochemical staining were used to detect cystatin C (Cys-C) and high density lipoprotein (HDL) in serum. The pathological changes of kidney were observed under microscope after hematoxylin-eosin (HE) staining, and ultrastructural changes of glomeruli and renal tubules were observed under electron microscope. After reoxygenation for 2 weeks, the above tests were repeated and compared. Results the level of Cys-C in group B was significantly higher than that in group A, and the level of HDL in group D was significantly lower than that in group A (P0.05), and the level of HDL in group D was significantly lower than that in group A (P0.05). But there was no significant difference (P0.05). The mean optical density of ERS marker protein chop in group C was significantly higher than that in group A (P0.05). There was no obvious abnormality in glomeruli in group B and C, and there was no obvious abnormality in small portion of edema of renal tubular epithelial cells and no obvious abnormality in D glomeruli, and most of renal tubular epithelial cells in group B were oedema. The focal nuclear pyknosis of proximal tubule epithelial cells in group B and C was observed under electron microscope. In group D, a large number of renal tubular epithelial nuclei were condensed and abscission. After reoxygenation, the level of Cys-C did not change significantly in group A and group B before reoxygenation (P0.05), but decreased significantly in group C and group D (P0.05), and the level of HDL decreased after reoxygenation in group A and group B before reoxygenation. But there was no significant difference (P0.05), in group C and before reoxygenation significantly increased (P0.05), in group D increased, but there was no significant difference (P0.05). Expression of chop protein in kidney after reoxygenation there was no significant difference between group A and group B (P0.05). Under light and electron microscope, there was no obvious abnormal edema in group B compared with that before reoxygenation, and the renal tissue was improved in group C before reoxygenation and in group D after reoxygenation. Conclusion 1. CIH combined with high fat diet can induce apoptosis of proximal tubule epithelium through activation of ERS, which can change the ultrastructure of kidney and then damage renal function. 2. CIH can induce apoptosis of proximal tubule epithelium by activation of ERS. Reoxygenation can improve renal structure and function by improving ERS.
【學位授予單位】：蘭州大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R766

【參考文獻】

相關期刊論文 前10條

1 閆曉娟;趙欣;李希平;魏永祥;;阻塞性睡眠呼吸暫停低通氣綜合征對腎素和醛固酮的影響[J];中國醫(yī)刊;2016年05期

2 石志輝;徐麟皓;周銳;;牛磺熊去氧膽酸鈉抑制小鼠間歇性低氧模型肺組織中內質網(wǎng)應激的激活[J];中南大學學報(醫(yī)學版);2015年11期

3 李婷;李秀翠;梁冬施;溫正旺;梅紅芳;曹紅超;蘇苗賞;蔡曉紅;;慢性間歇性低氧對大鼠腎臟氧化應激損傷及HIF-1α表達的影響[J];中國病理生理雜志;2015年02期

4 盧俏麗;薛蓉;董麗霞;任麗;周寧;程焱;;阻塞性睡眠呼吸暫停低通氣綜合征對缺血性腦血管病危險因素及認知功能的影響[J];中華老年心腦血管病雜志;2011年04期

5 王先酉;趙秀華;王峰;程臘梅;譚孟群;;高脂飲食引起大鼠動脈血管內皮細胞衰老[J];國際病理科學與臨床雜志;2010年02期

6 馮淑芝;田建立;張薔;張?zhí)N;陳寶元;;慢性間歇低氧對高脂飼料喂養(yǎng)大鼠不同器官超微結構的影響[J];中華結核和呼吸雜志;2010年04期

7 常曉東;甘華;杜曉剛;陳力學;;內質網(wǎng)應激在高脂血癥引起腎臟損害中的作用[J];西安交通大學學報(醫(yī)學版);2010年01期

8 余勤;汪小亞;岳紅梅;張佳賓;陽書坤;;血清胱蛋白酶抑制劑C及尿酶對阻塞性睡眠呼吸暫停低通氣綜合征早期腎功能損害的診斷價值[J];蘭州大學學報(醫(yī)學版);2008年01期

9 馮靖;陳寶元;郭美南;曹潔;趙海燕;梁東春;;間歇低氧氣體環(huán)境模型的建立[J];天津醫(yī)科大學學報;2006年04期

10 陳香美;王海燕;;提高慢性腎臟病的知曉率、治療率和控制率減輕對國民健康的危害[J];中華內科雜志;2006年06期

相關博士學位論文 前2條

1 吳艷艷;反復覺醒對心血管系統(tǒng)的影響：探究OSAHS患者心血管并發(fā)癥的發(fā)生機制[D];北京協(xié)和醫(yī)學院;2013年

2 丁巍;內質網(wǎng)應激在腎小管上皮細胞凋亡中的作用及機制研究[D];復旦大學;2012年

相關碩士學位論文 前6條

1 梁新元;血府逐瘀湯加減治療26例阻塞性睡眠呼吸暫停低通氣綜合征療效初探[D];北京中醫(yī)藥大學;2016年

2 黎嬌;氧化應激和交感神經(jīng)活性在阻塞性睡眠呼吸暫停低通氣綜合征合并高血壓發(fā)病機制中的作用[D];南昌大學醫(yī)學院;2015年

3 李蘭鳳;還原型谷胱甘肽對間歇低氧大鼠下丘腦—垂體—腎上腺軸超微結構及功能的干預機制研究[D];蘭州大學;2015年

4 王忠_";髓鞘堿性蛋白、β淀粉樣前體蛋白和腦啡肽在間歇低氧大鼠腦內的表達及還原型谷胱甘肽的保護作用[D];蘭州大學;2014年

5 邵川;慢性間歇低氧及再氧合對腎臟損害的機制研究[D];復旦大學;2011年

6 黃建釵;福州市20歲以上人群阻塞性睡眠呼吸暫停低通氣綜合征流行病學調查及危險因素分析[D];福建醫(yī)科大學;2009年

，

本文編號：2051420