本文關(guān)鍵詞：調(diào)控凝血活性對(duì)老年大鼠炎癥反應(yīng)影響的機(jī)制研究　出處：《中國人民解放軍軍醫(yī)進(jìn)修學(xué)院》2006年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 炎癥 纖維蛋白沉積 凝血酶受體 衰老 肺組織 腎臟

【摘要】：背景 凝血異常和纖維蛋白沉積見于人類許多類型的炎癥反應(yīng),并且與炎癥損害密切相關(guān),基礎(chǔ)研究表明,凝血系統(tǒng)參與炎癥調(diào)節(jié)。臨床資料和我們的前期研究發(fā)現(xiàn),老年機(jī)體存在高凝狀態(tài),同時(shí)老年個(gè)體較青年個(gè)體對(duì)各種炎癥刺激和病理損傷更加易感,因此我們推測(cè)老年個(gè)體的高凝狀態(tài)促進(jìn)了炎癥反應(yīng)。但老年個(gè)體高凝狀態(tài)的原因及其對(duì)老年個(gè)體炎癥反應(yīng)影響的機(jī)制目前尚不十分清楚。目的 為驗(yàn)證我們的假說,本研究首先觀察生理與炎癥狀態(tài)下老年大鼠肺組織和腎臟局部凝血活性的改變,探討老年機(jī)體高凝狀態(tài)形成的機(jī)制;其次,觀察調(diào)控凝血活性對(duì)炎癥的影響,從整體水平探討高凝狀態(tài)促進(jìn)老年大鼠炎癥反應(yīng)的機(jī)制;最后從細(xì)胞水平闡明凝血系統(tǒng)調(diào)節(jié)炎癥反應(yīng)的分子機(jī)制。方法 雌性Wistar 3月齡(青年鼠)和27月齡(老年鼠)大鼠均隨機(jī)分為正常對(duì)照組(NC組)、脂多糖組(L組)、脂多糖+氨甲環(huán)酸組(LT組)、脂多糖+氨甲環(huán)酸+肝素組(LTH組)、脂多糖+氨甲環(huán)酸+尿激酶組(LTU組)以及氨甲環(huán)酸組(T組)。以LPS腹腔注射誘導(dǎo)大鼠急性炎癥,并用氨甲環(huán)酸(TA)和肝素/或尿激酶(UK)調(diào)控凝血活性。分別采用免疫組化、Western Blot與Northern Blot檢測(cè)各指標(biāo)蛋白質(zhì)與基因表達(dá)。比較同一鼠齡組內(nèi)各處理組間以及相同處理的兩鼠齡組間纖溶酶原活化抑制物1(PAI-1)、血栓調(diào)節(jié)蛋白(TM)、凝血酶受體(TR)蛋白質(zhì)與mRNA表達(dá)水平和纖維蛋白沉積水平;以及浸潤的炎細(xì)胞數(shù)目、單核細(xì)胞趨化蛋白1(MCP-1)、細(xì)胞間粘附分子1(ICAM-1)蛋白質(zhì)和mRNA的表達(dá)。并在體外實(shí)驗(yàn)比較纖維蛋白和TR途徑對(duì)內(nèi)皮細(xì)胞ICAM-1表達(dá)和黏附單核細(xì)胞能力的影響。結(jié)果 (1)青年鼠和老年鼠NC組的肺組織和腎組織均無PAI-1表達(dá),而TM表達(dá)豐富;L組青年鼠和老年鼠肺組織和腎組織PAI-1的蛋白質(zhì)與mRNA表達(dá)水平均上調(diào),老年鼠上調(diào)幅度明顯高于青年鼠(P0.05),而青年鼠和老年鼠幾乎無TM表達(dá)。(2)青年鼠和老年鼠NC組的肺組織和腎組織均無纖維蛋白沉積,有少量TR表達(dá);兩鼠齡的L組纖維蛋白
[Abstract]:Background abnormal coagulation and fibrin deposition are found in many types of inflammatory reactions in humans and are closely related to inflammatory damage. Coagulation system is involved in inflammation regulation. Clinical data and our previous studies found that the elderly have hypercoagulable state, and elderly individuals are more susceptible to various inflammatory stimuli and pathological damage than young individuals. Therefore, we speculate that hypercoagulability promotes inflammation in elderly individuals, but the causes of hypercoagulability and the mechanism of its influence on inflammation in elderly individuals are still unclear. To test our hypothesis. In this study, we first observed the changes of local coagulation activity in lung tissue and kidney of aged rats under physiological and inflammatory conditions, and explored the mechanism of hypercoagulability in aged rats. Secondly, the effect of regulating coagulation activity on inflammation was observed, and the mechanism of hypercoagulability promoting inflammation in aged rats was discussed from the whole level. Finally, the molecular mechanism of coagulation system regulating inflammatory response was elucidated at the cellular level. Methods female Wistar 3-month-old (young) and 27-month-old (aged) rats were randomly divided into normal control group (P < 0.05). NC group). Lipopolysaccharide group (L group), lipopolysaccharide formic acid group (LT group), lipopolysaccharide carbamate heparin group (LTH group). The acute inflammation was induced by intraperitoneal injection of LPS. The coagulation activity was regulated by TAA and UK. Immunohistochemistry was used respectively. Western Blot and Northern. Blot was used to detect the expression of protein and gene. Plasminogen activator inhibitor 1 (plasminogen activator inhibitor 1) was compared between different treatment groups within the same age group and two groups with the same treatment. PAI-1). Thrombomodulin (TMN), thrombin receptor (TRT) protein and mRNA expression level and fibrin deposition level; And the number of infiltrating inflammatory cells, monocyte chemoattractant protein (MCP-1). Intercellular adhesion molecule 1 (ICAM-1). Expression of protein and mRNA. Effects of fibrin and tr pathway on ICAM-1 expression and monocyte adhesion in endothelial cells were compared in vitro. There was no PAI-1 expression in lung and kidney tissues of young rats and old rats in NC group. The expression of TM was abundant. In group L, the expression of PAI-1 protein and mRNA was up-regulated in lung and kidney tissues of young and aged rats, and the up-regulation of mRNA in aged rats was significantly higher than that in young rats (P0.05). However, there was almost no TM expression in young rats and aged rats. (2) there was no fibrin deposition in lung and kidney tissues of young rats and old rats in NC group, but a small amount of tr expression. L-Group Fibrin of two Rat Ages
【學(xué)位授予單位】：中國人民解放軍軍醫(yī)進(jìn)修學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類號(hào)】：R363

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