本文選題：尿毒癥 + 血管鈣化　； 參考：《天津醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：心血管疾病(cardiovascular disease, CVD)是終末期腎臟病(end-stage renal disease, ESRD)的主要死因,大約50%ESRD患者死于CVD,是普通人群的20-30倍。因此,有關(guān)ESRD心血管并發(fā)癥的原因及防治措施一直是國(guó)內(nèi)外學(xué)者探討的的重點(diǎn)課題。血管鈣化是ESRD患者發(fā)生CVD的獨(dú)立危險(xiǎn)因素�，F(xiàn)有研究認(rèn)為,影響CKD患者血管鈣化的因素除了傳統(tǒng)因素(如高血壓、脂代謝異常、糖尿病,高齡、吸煙)外,還包括非傳統(tǒng)因素,如鈣磷代謝異常、氧化應(yīng)激、炎癥介質(zhì)等。NF-κB是炎癥的重要介質(zhì)。已經(jīng)證實(shí),NF-κB參與了尿毒癥血管鈣化過(guò)程。本研究旨在探討NF-κB抑制劑吡咯烷二硫代甲酸銨(PDTC)對(duì)尿毒癥大鼠主動(dòng)脈鈣化的干預(yù)作用及相關(guān)機(jī)制。 方法：16只雄性Sprague-Dawley大鼠,隨機(jī)分為尿毒癥模型組及PDTC干預(yù)組,均以0.75%腺嘌呤及高磷飲食喂養(yǎng),制備尿毒癥動(dòng)脈鈣化模型,干預(yù)組同時(shí)腹腔注射PDTC100mg/kg/d。另取8只匹配大鼠作為健康對(duì)照組。8周后處死大鼠,HE及von Kossa染色觀察腹主動(dòng)脈病理改變及鈣化情況,免疫組織化學(xué)方法檢測(cè)OPN、Cbfa-1在主動(dòng)脈的定位表達(dá),Western印跡檢測(cè)主動(dòng)脈NF-κB總p65與細(xì)胞核p-p65、骨橋蛋白(OPN)、核心結(jié)合因子al (Cbfa-1)蛋白表達(dá)。 結(jié)果：造模4周及8周,尿毒癥組、PDTC干預(yù)組大鼠血清Scr、血磷、鈣磷乘積均顯著高于對(duì)照組(均P0.01),但此兩組間差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)；給藥8周,主動(dòng)脈均出現(xiàn)明顯鈣化,以中膜鈣化為主,但PDTC干預(yù)組程度較輕(P0.05)；免疫組化顯示,大鼠主動(dòng)脈OPN表達(dá)于中膜及外膜,Cbfa-1表達(dá)于中膜細(xì)胞核,二者在PDTC干預(yù)組表達(dá)均較尿毒癥組下降(均P0.05)；Western印跡結(jié)果顯示,PDTC干預(yù)組主動(dòng)脈NF-κB總p65、核p-p65、OPN、Cbfa-1表達(dá)均較尿毒癥組下降(均P0.01),且Cbfa-1表達(dá)與p65、核p-p65表達(dá)均呈正相關(guān)(r=0.707, P=0.000; r=0.507, P=0.000)。 結(jié)論：PDTC可部分阻斷NF-κB p65核轉(zhuǎn)位所致尿毒癥大鼠血管平滑肌細(xì)胞向成骨細(xì)胞轉(zhuǎn)分化及主動(dòng)脈鈣化。
[Abstract]:Objective: cardiovascular disease (CVD) is the main cause of death of end-stage renal disease, ESRD) in end-stage renal disease, about 20-30 times of that in the general population. Therefore, the causes and preventive measures of cardiovascular complications in ESRD have been the focus of domestic and foreign scholars. Vascular calcification is an independent risk factor for CVD in patients with ESRD. Current studies suggest that the factors affecting vascular calcification in patients with CKD include non-traditional factors, such as abnormal calcium and phosphorus metabolism, oxidative stress, in addition to traditional factors (such as hypertension, abnormal lipid metabolism, diabetes, old age, smoking). NF- 魏 B is an important mediator of inflammation. NF- 魏 B has been confirmed to be involved in the vascular calcification process in uremia. The aim of this study was to investigate the effect of NF- 魏 B inhibitor, ammonium pyrrolidine dithiocarbamate, on aortic calcification in uremic rats. Methods Sixteen male Sprague-Dawley rats were randomly divided into two groups: uremic model group and PDTC intervention group. The rats were fed with 0.75% adenine and high phosphorus diet to establish the model of arterial calcification of uremia. The intervention group was injected with PDTC 100 mg / kg / d intraperitoneally at the same time. In addition, 8 matched rats were used as control group. After 8 weeks, the rats were killed to observe the pathological changes and calcification of abdominal aorta by HE and von Kossa staining. The expression of OPN- Cbfa-1 in aorta was detected by immunohistochemical method. Western blot was used to detect the expression of total p65 of NF- 魏 B and p-p65 in nucleus, OPN of osteopontin and Cbfa-1). Results: after 4 and 8 weeks of modeling, the serum Scrs, serum phosphorus, calcium and phosphorus products in the uremic group were significantly higher than those in the control group (P 0.01), but there was no significant difference between the two groups (P 0.05), and at 8 weeks of administration, calcification was observed in the aorta. Medial calcification was predominant, but the degree of PDTC intervention group was mild (P0.05A), and the expression of OPN in rat aorta was found in the medial membrane and adventitia Cbfa-1 in the nucleus of the mesangium, and the expression of Cbfa-1 in the rat aorta was observed by immunohistochemistry. The expression of NF- 魏 B in aorta of PDTC intervention group was lower than that of uremia group (P 0.05). The expression of Cbfa-1 in nucleus p-p65 was significantly lower than that in uremia group (P 0.01), and the expression of Cbfa-1 was positively correlated with p65. The expression of nuclear p-p65 was positively correlated with that of P0. 707, P0. 000, rn 0. 507, P0. 000. Conclusion the osteoblast transdifferentiation and aortic calcification of vascular smooth muscle cells induced by nuclear translocation of NF- 魏 B p65 in rats with uremia were partially blocked by 1: PDTC.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R692.5

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