IL-22調(diào)控枯否細(xì)胞極化抑制肝纖維化的機(jī)制研究
發(fā)布時(shí)間:2021-03-23 12:32
肝纖維化是肝臟慢性炎癥損傷時(shí)引發(fā)持續(xù)性損傷修復(fù)反應(yīng),導(dǎo)致肝組織內(nèi)細(xì)胞外基質(zhì)異常沉積,進(jìn)一步引發(fā)肝臟結(jié)構(gòu)和肝功能異常改變的一種病理過程。肝纖維化時(shí)多種免疫因子的失衡導(dǎo)致和促進(jìn)了肝纖維化的發(fā)生和發(fā)展。研究表明,巨噬細(xì)胞具有高度的可塑性,在不同的免疫內(nèi)環(huán)境作用下可極化成不同的表型并發(fā)揮不同的功能。如脂多糖(lipopolysaccharides,LPS)及IFN-γ可促進(jìn)巨噬細(xì)胞分化成經(jīng)典活化的M1型;M1型巨噬細(xì)胞可產(chǎn)生炎癥因子促進(jìn)機(jī)體炎癥反應(yīng);而IL-4及IL-13可誘導(dǎo)巨噬細(xì)胞分化成選擇性活化的M2型,M2型巨噬細(xì)胞可產(chǎn)生抗炎因子如IL-10、TGF-β減輕炎癥反應(yīng),減少氧化應(yīng)激、炎癥損傷及促進(jìn)組織修復(fù)。枯否細(xì)胞(Kupffer cells,KCs)是體內(nèi)最大的組織巨噬細(xì)胞群,是肝臟固有免疫系統(tǒng)的重要功能細(xì)胞。臨床研究及動(dòng)物實(shí)驗(yàn)已經(jīng)證實(shí)在酒精性及非酒精性脂肪肝病中,M1型KCs細(xì)胞可促進(jìn)肝細(xì)胞的脂肪變性及凋亡,炎性細(xì)胞募集,從而導(dǎo)致纖維化,而限制M1型KC...
【文章來源】:廣西醫(yī)科大學(xué)廣西壯族自治區(qū)
【文章頁(yè)數(shù)】:177 頁(yè)
【學(xué)位級(jí)別】:博士
【部分圖文】:
人體肝組織IL-22免疫熒光染色Figure1IL-22immunofluorescencestainingofhumanlivertissue(2)M1型KCs(F4/80+/iNOS+)(圖2)及M2型KCs(F4/80+/CD206+)(圖3)
人體肝組織M1型KCs免疫熒光染色Figure2M1-KCsimmunofluorescencestainingofhumanlivertissue
圖 3 人體肝組織 M2型 KCs 免疫熒光染色Figure 3 M2-KCs immunofluorescence staining of human liver tissue(3)M2/M1比值隨著肝纖維化的進(jìn)展呈現(xiàn)峰值改變,其中該比值在 G2S2 期(0.62%±0.08%)最高,與 control 組(0.34%±0.05%)比較具有顯著統(tǒng)計(jì)學(xué)差異(P<0.01)(圖 4-e)。
【參考文獻(xiàn)】:
期刊論文
[1]Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines[J]. Dong-Hong Lu,Xiao-Yun Guo,Shan-Yu Qin,Wei Luo,Xiao-Li Huang,Mei Chen,Jia-Xu Wang,Shi-Jia Ma,Xian-Wen Yang,Hai-Xing Jiang. World Journal of Gastroenterology. 2015(05)
[2]Effects of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease and inflammation[J]. Xing-Chun Wang,Aaron M Gusdon,Huan Liu,Shen Qu. World Journal of Gastroenterology. 2014(40)
[3]FXR agonist GW4064 alleviates endotoxin-induced hepatic inflammation by repressing macrophage activation[J]. Jun Yao,Chun-Suo Zhou,Xiong Ma,Bai-Qing Fu,Li-Sheng Tao,Miao Chen,Ya-Ping Xu. World Journal of Gastroenterology. 2014(39)
[4]Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet[J]. Hideto Kawaratani,Tatsuhiro Tsujimoto,Toshiyuki Kitazawa,Mitsuteru Kitade,Hitoshi Yoshiji,Masahito Uemura,Hiroshi Fukui. World Journal of Gastroenterology. 2008(43)
[5]Role of Kupffer cells in the pathogenesis of liver disease[J]. George Kolios,Vassilis Valatas,Elias Kouroumalis. World Journal of Gastroenterology. 2006(46)
本文編號(hào):3095798
【文章來源】:廣西醫(yī)科大學(xué)廣西壯族自治區(qū)
【文章頁(yè)數(shù)】:177 頁(yè)
【學(xué)位級(jí)別】:博士
【部分圖文】:
人體肝組織IL-22免疫熒光染色Figure1IL-22immunofluorescencestainingofhumanlivertissue(2)M1型KCs(F4/80+/iNOS+)(圖2)及M2型KCs(F4/80+/CD206+)(圖3)
人體肝組織M1型KCs免疫熒光染色Figure2M1-KCsimmunofluorescencestainingofhumanlivertissue
圖 3 人體肝組織 M2型 KCs 免疫熒光染色Figure 3 M2-KCs immunofluorescence staining of human liver tissue(3)M2/M1比值隨著肝纖維化的進(jìn)展呈現(xiàn)峰值改變,其中該比值在 G2S2 期(0.62%±0.08%)最高,與 control 組(0.34%±0.05%)比較具有顯著統(tǒng)計(jì)學(xué)差異(P<0.01)(圖 4-e)。
【參考文獻(xiàn)】:
期刊論文
[1]Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines[J]. Dong-Hong Lu,Xiao-Yun Guo,Shan-Yu Qin,Wei Luo,Xiao-Li Huang,Mei Chen,Jia-Xu Wang,Shi-Jia Ma,Xian-Wen Yang,Hai-Xing Jiang. World Journal of Gastroenterology. 2015(05)
[2]Effects of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease and inflammation[J]. Xing-Chun Wang,Aaron M Gusdon,Huan Liu,Shen Qu. World Journal of Gastroenterology. 2014(40)
[3]FXR agonist GW4064 alleviates endotoxin-induced hepatic inflammation by repressing macrophage activation[J]. Jun Yao,Chun-Suo Zhou,Xiong Ma,Bai-Qing Fu,Li-Sheng Tao,Miao Chen,Ya-Ping Xu. World Journal of Gastroenterology. 2014(39)
[4]Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet[J]. Hideto Kawaratani,Tatsuhiro Tsujimoto,Toshiyuki Kitazawa,Mitsuteru Kitade,Hitoshi Yoshiji,Masahito Uemura,Hiroshi Fukui. World Journal of Gastroenterology. 2008(43)
[5]Role of Kupffer cells in the pathogenesis of liver disease[J]. George Kolios,Vassilis Valatas,Elias Kouroumalis. World Journal of Gastroenterology. 2006(46)
本文編號(hào):3095798
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