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

【摘要】：目的通過研究間歇性低氧(IH)對大鼠肝臟的損傷及脂肪因子chemerin表達(dá)的影響,探討非酒精性脂肪性肝病(NAFLD)與脂肪因子chemerin表達(dá)的內(nèi)在關(guān)系,并研究復(fù)氧的干預(yù)作用,為臨床上OSAHS及其相關(guān)代謝性并發(fā)癥的進(jìn)一步研究及防治提供新的思路。方法選取48只健康的雄性Wistar大鼠,根據(jù)隨機數(shù)字表法隨機分為4組(n=12):常氧+普通飲食組(NC+ND組)、常氧+高脂飲食組(NC+HFD組)、間歇低氧+普通飲食組(IH+ND組)、間歇低氧+高脂飲食組(IH+HFD組)。普通飲食組給予基礎(chǔ)飼料喂養(yǎng),高脂飲食組予以高脂飼料喂養(yǎng)。IH組置于8h/d的間歇性低氧環(huán)境中,同時NC組給予間歇壓縮空氣。實驗6周末各組處死一半大鼠,稱量體重、肝濕重,計算肝指數(shù),采集動脈血及肝組織標(biāo)本,使用全自動生化分析儀檢測大鼠肝酶、血脂水平,空腹血糖(FPG)通過葡萄糖氧化酶法檢測,空腹胰島素(FINS)使用放射免疫法測定,用胰島素敏感指數(shù)(ISI)及胰島素抵抗指數(shù)(IRI)系統(tǒng)評價胰島素抵抗,光鏡、透射電鏡觀察肝臟組織形態(tài)學(xué)及超微結(jié)構(gòu)改變,ELISA(雙抗體夾心法)檢測大鼠血清及肝組織chemerin的表達(dá)。余IH組大鼠予以復(fù)氧干預(yù)2周,普通飲食組繼續(xù)給予基礎(chǔ)飼料喂養(yǎng),高脂飲食組予以高脂飼料喂養(yǎng),實驗8周末處死剩余大鼠,各檢測指標(biāo)及檢測方法同上所述。結(jié)果1.與NC+ND組相比,IH+ND組大鼠血清ALT、AST、FPG、FINS、IRI、TC、TG、LDL-C均顯著升高;與NC+HFD組相比,IH+HFD組大鼠血清AST、FINS、IRI水平升高;與IH+ND組相比,IH+HFD組大鼠血清AST、FPG、TC均升高,LDL-C水平顯著升高。余各項指標(biāo)間未見明顯差異。2.與NC+ND組相比,在光學(xué)顯微鏡和透射電子顯微鏡下,NC+HFD組、IH+ND組和IH+HFD組大鼠肝組織學(xué)特點均表現(xiàn)為非酒精性脂肪性肝病:NC+HFD組表現(xiàn)為單純性脂肪肝;IH+ND組表現(xiàn)為脂肪性肝炎,IH+HFD組損傷表現(xiàn)均明顯重于IH+ND組和NC+HFD組,表現(xiàn)為脂肪性肝炎甚至輕度肝臟纖維化。3.與NC+ND組相比,IH+ND組大鼠血清chemerin表達(dá)水平顯著升高;與NC+HFD組和IH+ND組相比,IH+HFD組大鼠血清chemerin水平亦有顯著表達(dá)。其余各項指標(biāo)間未見明顯統(tǒng)計學(xué)意義。4.大鼠血清chemerin表達(dá)水平與ALT(r=0.526)呈正相關(guān),與AST(r=0.742)、FPG(r=0.751)、FINS(r=0.764)、IRI(r=0.765)、TC(r=0.791)、LDL-C(r=0.818)、體重(r=0.685)呈明顯正相關(guān),與ISI(r=-0.692)呈明顯負(fù)相關(guān)。5.以是否發(fā)生OSAHS相關(guān)NAFLD為因變量,以肝重、體重、LBR、AST、ALT、FPG、FINS、IRI、ISI、TC、TG、LDL-C、血清chemerin及肝臟chemerin為自變量,行Logistic逐步回歸分析后得出結(jié)果,血清chemerin的表達(dá)是發(fā)生OSAHS相關(guān)NAFLD的危險因素(OR=1.197,P0.01)。6.與復(fù)氧前相比,復(fù)氧后IH+ND組大鼠體重升高,IRI水平降低,血清FPG、血清chemerin表達(dá)水平顯著降低,在光學(xué)顯微鏡和透射電子顯微鏡下,肝組織學(xué)特點仍表現(xiàn)為脂肪性肝炎;與復(fù)氧前相比,復(fù)氧后IH+HFD組大鼠血清FPG水平降低,血清chemerin表達(dá)水平顯著降低,肝組織學(xué)特點亦仍表現(xiàn)為脂肪性肝炎甚至輕度肝臟纖維化。結(jié)論1.間歇性低氧可導(dǎo)致大鼠發(fā)生糖脂代謝紊亂及肝損傷,主要表現(xiàn)為NAFLD,在間歇性低氧合并高脂飲食的情況下,這種代謝紊亂與肝損傷更為嚴(yán)重。提示間歇性低氧可能是NAFLD發(fā)生與進(jìn)展的獨立危險因素。2.暴露于間歇性低氧條件下的大鼠發(fā)生OSAHS相關(guān)NAFLD時,血清chemerin水平呈高表達(dá)狀態(tài),肝臟chemerin水平無顯著變化,行Logistic逐步回歸分析結(jié)果顯示,血清chemerin是發(fā)生NAFLD的危險因素,提示血清chemerin可作為早期預(yù)測OSAHS相關(guān)NAFLD的脂肪因子。3.兩周的復(fù)氧干預(yù)治療并不能引起大鼠肝臟病理表現(xiàn)和血清轉(zhuǎn)氨酶水平的明顯改觀,但可以降低FPG水平,甚至減輕胰島素抵抗,并使得血清chemerin表達(dá)水平顯著下降,提示短期CPAP治療無法有效改善OSAHS相關(guān)NAFLD,但在一定程度上可能會穩(wěn)定和延緩其進(jìn)展,血清chemerin可能作為未來治療OSAHS相關(guān)NAFLD新的非侵入性標(biāo)記物。
[Abstract]:Objective to study the effect of intermittent hypoxia (IH) on the liver injury and the expression of fat factor Chemerin in rats, to explore the intrinsic relationship between the expression of nonalcoholic fatty liver disease (NAFLD) and fat factor Chemerin, and to study the intervention of reoxygenation, and provide a new method for the further study and prevention of the clinical OSAHS and its related metabolic complications. Methods 48 healthy male Wistar rats were randomly divided into 4 groups (n=12): normal oxygen + ordinary diet group (group NC+ND), normal oxygen + high fat diet group (group NC+HFD), intermittent hypoxia + ordinary diet group (IH+ND group), intermittent hypoxia + high fat diet group (group IH+HFD). The ordinary diet group was given basic feed, high fat drink. The diet group was given high fat diet for.IH group to be placed in the intermittent hypoxia environment of 8h/d, while group NC was given intermittent compressed air. At the end of the 6 week, half of the rats were killed, weighing weight, liver wet weight, calculating liver index, collecting arterial blood and liver tissue specimens, using an automatic biochemical analyzer to detect rat liver enzyme, blood lipid level, fasting blood glucose (FPG Through the glucose oxidase assay, the fasting insulin (FINS) was measured by radioimmunoassay, insulin resistance index (ISI) and insulin resistance index (IRI) system were used to evaluate insulin resistance, light microscopy and transmission electron microscopy were used to observe the changes of the liver histomorphology and ultrastructure, and the ELISA (double antibody sandwich method) was used to detect the chemer in the serum and liver tissue of rats. The expression of in. The rats in group IH were treated with reoxygenation for 2 weeks. The normal diet group continued to feed the basal diet, the high fat diet group was fed with high fat diet, and the remaining rats were killed at the end of the 8 week. The results 1. were compared with the NC+ND group. The serum ALT, AST, FPG, FINS, IRI, TC, TG, LDL-C were all significant compared with the group IH+ND. The level of serum AST, FINS and IRI in group IH+HFD was higher than that in group NC+HFD. Compared with group IH+ND, the serum AST, FPG, TC of rats in group IH+HFD increased and LDL-C level increased significantly. The histological features were all nonalcoholic fatty liver disease: NC+HFD group showed simple fatty liver, IH+ND group showed fatty hepatitis, and group IH+HFD was significantly more serious than group IH+ND and NC+HFD group. The expression of.3. in fatty hepatitis and even mild liver fibrosis was compared with that of group NC+ND, and the serum Chemerin expression level of IH+ND group was significantly higher than that of group NC+ND. As compared with group NC+HFD and group IH+ND, the level of serum Chemerin in group IH+HFD was also significantly expressed. There was no significant statistical significance between the other indexes. The level of Chemerin expression in the serum of.4. rats was positively correlated with the ALT (r=0.526) and AST (r=0.742), FPG (r=0.751). 685) there was a significant positive correlation and a significant negative correlation with ISI (r=-0.692), which was negatively correlated with.5., with the occurrence of OSAHS related NAFLD as the dependent variable, with liver weight, weight, LBR, AST, ALT, FPG, FINS, IRI, ISI, serum and liver as independent variables. The risk factors (OR=1.197, P0.01).6. were compared with that before reoxygenation. After reoxygenation, the body weight of the rats in the IH+ND group, the IRI level, the serum FPG, the serum Chemerin expression level decreased significantly. The histological characteristics of the liver were still fatty hepatitis in the optical microscope and transmission electron microscope, and the serum FPG in IH+HFD group after reoxygenation was compared with the reoxygenation. The level of serum Chemerin expression decreased significantly and the liver histology was still characterized by fatty hepatitis and even mild liver fibrosis. Conclusion 1. intermittent hypoxia can lead to glucose and lipid metabolism disorder and liver injury in rats. The main manifestation is NAFLD. In the case of intermittent hypoxic combined with high fat diet, this metabolic disorder and liver disease It is suggested that intermittent hypoxia may be an independent risk factor for the occurrence and progression of NAFLD. When.2. exposure to intermittent hypoxia, the level of serum Chemerin is highly expressed, and the level of Chemerin in the liver is not significantly changed. The result of Logistic stepwise regression analysis shows that serum Chemerin is the hair of hair. The risk factors of birth NAFLD suggest that serum Chemerin can be used as an early prediction of OSAHS related NAFLD for.3. two weeks of reoxygenation, which can not cause a significant change in liver pathological manifestation and serum transaminase level, but can reduce the level of FPG, even reduce islet resistance, and make the level of serum Chemerin significant. Decline, suggesting that short term CPAP therapy does not effectively improve OSAHS related NAFLD, but may stabilize and delay its progress to a certain extent. Serum Chemerin may be a new noninvasive marker for the future treatment of OSAHS related NAFLD.

【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R575;R766

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