本文選題：縮膽囊素 + 腫瘤壞死因子　； 參考：《河北醫(yī)科大學(xué)》2006年博士論文

【摘要】： 類風(fēng)濕關(guān)節(jié)炎(rheumatoid arthritis RA)的主要病變在關(guān)節(jié),在關(guān)節(jié)內(nèi)可以看到滑膜組織異常增生、大量炎性細胞浸潤以及軟骨與骨進行性破壞,在關(guān)節(jié)外則表現(xiàn)為血管炎。疾病過程綜合體現(xiàn)了滑膜組織增生、炎癥、自身免疫這三種病理生理過程,它們之間相互作用、相互關(guān)聯(lián),形成了一個錯綜復(fù)雜的網(wǎng)絡(luò)機制。成纖維樣滑膜細胞(fibroblast-like synoviocytes,FLSs)是從RA滑膜中分離得到的外觀類似成纖維細胞的一類滑膜細胞。目前認為,RA FLSs過度增生是造成滑膜增厚的主要原因。FLSs分泌IL-6、IL-8、粒-巨噬細胞集落刺激因子( granulocyte-macrophage colony-stimulating factor,GM-CSF)、前列腺素(prostaglandins,PGs)、基質(zhì)金屬蛋白酶(matrix metalloproteinases,MMPs)以及聚合素酶(aggrecanase)和組織蛋白酶等效應(yīng)分子,對骨與軟骨組織造成侵蝕,FLSs被認為是介導(dǎo)RA關(guān)節(jié)破壞的主要效應(yīng)細胞,而TNF-α則是參與FLSs反應(yīng)的關(guān)鍵性細胞因子。FLSs增殖和分泌在RA發(fā)病過程中發(fā)揮關(guān)鍵性作用。所以尋找具有調(diào)節(jié)FLSs上述功能的抗炎制劑已成為研究的熱點。八肽膽囊收縮素(cholecystokinin octapeptide,CCK-8)是一種內(nèi)源性腦腸肽,近年研究表明CCK-8具有抗炎和免疫調(diào)節(jié)作用。已有報道CCK-8對角叉菜膠誘導(dǎo)的大鼠關(guān)節(jié)炎有緩解作用。本室先前研究表明,CCK-8對TNF-α誘導(dǎo)膠原性關(guān)節(jié)炎(collagen-induced arthritis, CIA)大鼠滑膜細胞增殖及大鼠成纖維樣滑膜細胞RSC-364增殖和MMP-2、MMP-9分泌皆有抑制作用,提示CCK-8對RA可能具有積極的藥理作用。 MMPs和MMPs組織抑制劑(tissue inhibitor of MMPs,TIMPs)系統(tǒng)失衡在RA軟骨破壞中起關(guān)鍵作用。CCK-8對MMPs/ TIMPs系統(tǒng)有何影響,尚未見報道。調(diào)控MMPs表達及合成的信號轉(zhuǎn)導(dǎo)機制極其復(fù)雜,它們往往同時參與RA其它炎性介質(zhì)的合成及細胞增殖等過程。已知活化蛋白-1(activator protein-1, AP-1)是參與TNF-α誘導(dǎo)RA滑膜細胞MMPs基因表達、增殖及炎癥反應(yīng)的一個十分重要的轉(zhuǎn)錄因子。本室前期研究發(fā)
[Abstract]:The main lesions of rheumatoid arthritis RAA are in the joint. The synovial tissue is abnormally proliferated, a large number of inflammatory cells infiltrate, and the cartilage and bone are destroyed progressively in the joint, and the vasculitis is seen outside the joint. The disease process embodies three pathophysiological processes of synovial tissue proliferation inflammation and autoimmunity which interact and correlate with each other and form a complicated network mechanism. Fibroblast-like synoviocytes-FLSs (fibroblast-like synoviocytes-FLSs) are fibroblast-like synoviocytes-like synovial cells isolated from RA synoviocytes. At present, it is believed that the excessive proliferation of RA FLSs is the main cause of synovial thickening. FLSs secrete IL-6 and IL-8, granulocyte-macrophage colony-stimulating factor-GM-CSFN, prostaglandins, matrix metalloproteinases, polymerase aggrecanase and cathepsin, etc. FLSs are considered to be the main effector cells involved in the destruction of RA joints, and TNF- 偽 is the key cytokine involved in the FLSs response. FLSs proliferation and secretion play a key role in the pathogenesis of RA. Therefore, the search for anti-inflammatory agents with the function of regulating FLSs has become a hot spot. Cholecystokinin octapeptidein (CCK-8) is an endogenous brain-gut peptide. Recent studies have shown that CCK-8 has anti-inflammatory and immunomodulatory effects. It has been reported that CCK-8 can relieve arthritis induced by carrageenin in rats. Previous studies in our laboratory showed that CCK-8 inhibited the proliferation of synovial cells and the secretion of MMP-2 MMP-9 in fibroblast synoviocytes and collagen-induced synovial cells induced by TNF- 偽 in rats, suggesting that CCK-8 may have a positive pharmacological effect on RA. MMPs and tissue inhibitor of MMPs tissue inhibitor of tissue TIMPs) system imbalance plays a key role in RA cartilage damage. How CCK-8 affects MMPs/ TIMPs system has not been reported. The mechanism of signal transduction regulating MMPs expression and synthesis is very complicated, and they are often involved in the synthesis of other inflammatory mediators of RA and the proliferation of RA cells at the same time. Activator protein-1 (AP-1) is known to be a very important transcription factor involved in the expression, proliferation and inflammatory response of MMPs gene in RA synovial cells induced by TNF- 偽. Prophase research in this room
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2006
【分類號】：R363

【參考文獻】

相關(guān)期刊論文 前10條

1 金玉懷,趙占勝,徐錦榮,劉品力,李淑瑾,凌亦凌,叢斌;八肽膽囊收縮素對大鼠滑膜細胞株RSC-364增生的影響及其可能的分子機制[J];中華風(fēng)濕病學(xué)雜志;2003年03期

2 金玉懷,趙占勝,叢斌,徐錦榮,姚玉霞,李淑瑾,凌亦凌;八肽膽囊收縮素對大鼠滑膜細胞株RSC-364基質(zhì)金屬蛋白酶-2和-9產(chǎn)生的影響[J];中華風(fēng)濕病學(xué)雜志;2005年04期

3 陳大慶,倪宏;縮膽囊素生物學(xué)作用的多樣性[J];國外醫(yī)學(xué)(兒科學(xué)分冊);2002年03期

4 孟愛宏,凌亦凌,趙曉云,單保恩;絲裂素活化蛋白激酶在膽囊收縮素對脂多糖刺激小鼠脾細胞增殖中的作用[J];河北醫(yī)科大學(xué)學(xué)報;2002年01期

5 趙占勝,金玉懷,徐錦榮,李淑瑾,于丹軍,凌亦凌,叢斌;八肽膽囊收縮素對大鼠滑膜細胞株RSC-364分泌IL-6的影響[J];基礎(chǔ)醫(yī)學(xué)與臨床;2003年01期

6 倪志宇,李淑瑾,叢斌,姚玉霞,王春艷;CC-K8抑制LPS誘導(dǎo)的大鼠肺間質(zhì)巨噬細胞TLR4及IL-1β的表達[J];基礎(chǔ)醫(yī)學(xué)與臨床;2005年02期

7 凌亦凌，黃善生，王樂豐，張君嵐，萬梅，，郝榮利;八肽膽囊收縮素抗內(nèi)毒素休克的實驗研究[J];生理學(xué)報;1996年04期

8 項鵬,陳曼玲,吳兆鋒;膽囊收縮素8對大鼠大腦皮質(zhì)細胞鈣調(diào)素和蛋白激酶C活性的影響[J];中國生物化學(xué)與分子生物學(xué)報;2001年04期

9 金玉懷;趙占勝;叢斌;徐錦榮;姚玉霞;李淑瑾;凌亦凌;;八肽膽囊收縮素對大鼠滑膜細胞株RSC-364 TNF受體基因表達的影響[J];中國生物制品學(xué)雜志;2006年03期

10 叢斌,凌亦凌,谷振勇,王俊霞,姚玉霞;八肽膽囊收縮素對脂多糖誘導(dǎo)大鼠肺組織NF-κB活性增高的抑制作用[J];中國病理生理雜志;2002年06期

相關(guān)博士學(xué)位論文 前3條

1 高維娟;CCK-8抗炎作用的受體及cAMP-PKA信號轉(zhuǎn)導(dǎo)機制研究[D];河北醫(yī)科大學(xué);2004年

2 倪志宇;CCK-8對炎癥反應(yīng)中促炎及抗炎性細胞因子表達的調(diào)控機制研究[D];河北醫(yī)科大學(xué);2005年

3 鄭詠秋;大鼠佐劑性關(guān)節(jié)炎滑膜細胞G蛋白偶聯(lián)信號通路與MAPK信號通路的關(guān)系及白芍總苷的作用[D];安徽醫(yī)科大學(xué);2004年

本文編號：1862821