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(xué)》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(jī)制以及復(fù)氧后腎臟組織結(jié)構(gòu)以及腎臟功能的恢復(fù)。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(nèi)質(zhì)網(wǎng)應(yīng)激反應(yīng)(ERS)介導(dǎo)大鼠腎臟的損傷;并以復(fù)氧模擬臨床持續(xù)氣道內(nèi)正壓通氣(CPAP)治療,觀察腎臟組織結(jié)構(gòu)及功能的恢復(fù)。為臨床的治療提供新的診療思路。方法將48只SPF級(jí)健康的雄性Wistar大鼠,隨機(jī)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(jī)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(jié)構(gòu)變化,以及電鏡下觀察腎小球及腎小管超微結(jié)構(gòu)變化。再在原飲食條件下復(fù)氧2周,再次重復(fù)上述檢測,并進(jìn)行比較。結(jié)果B組、C組、D組中腎早損指標(biāo)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(biāo)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(biāo)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(xì)胞小部分水腫,D腎小球未見明顯異常,組腎小管上皮細(xì)胞大部分水腫;電鏡下觀察,B組、C組近曲腎小管上皮細(xì)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(xì)胞核固縮,刷狀緣稀疏并脫落。并復(fù)氧2周后Cys-C水平在A組、B組與復(fù)氧前比較無顯著變化(均P0.05),在C組、D組中與復(fù)氧前比較顯著降低(均P0.05);復(fù)氧后HDL水平在A組、B組與復(fù)氧前比較有下降,但無顯著性差異(均P0.05),在C組與復(fù)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(fù)氧后CHOP蛋白平均光密度水平在腎臟中的表達(dá),A組、B組水平與復(fù)氧前無明顯差異(均P0.05),C組、D組水平與復(fù)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(fù)氧前比較水腫稍有加重,復(fù)氧前C組、D組與復(fù)氧后比較腎臟組織改善。結(jié)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(dǎo)近曲腎小管上皮的凋亡,使腎臟的超微結(jié)構(gòu)發(fā)生改變,進(jìn)而腎臟功能損傷。3.復(fù)氧可通過改善ERS,使腎臟結(jié)構(gòu)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(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R766

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