卡维地洛改善肝硬化肝内血管阻力的结构性因素和降低门静脉压力的作用及机制研究
发布时间：2022-02-14 16:57
研究背景和目的 肝硬化是肝纤维化的进展阶段,是慢性肝病共同的病理过程,属于发病率和死亡率均较高的疾病。门静脉高压（portal hypertension,PHT）是肝硬化最常见和最严重的并发症,可导致严重的临床问题,例如曲张静脉破裂出血、腹水和肝性脑病等。肝硬化门脉高压及其并发症是慢性肝病患者死亡和需要肝移植的首要原因。能够延缓甚至逆转肝硬化的药物,对于延长肝硬化患者的生存时间,改善患者的生活质量,具有重要的临床意义。近些年来关于肝硬化门脉高压发病机制的研究取得了极大的进展。PHT的发病机制包括两方面:一是起始因素,即肝内血管阻力（intrahepatic vascular resistance,IHVR）的增加;二是维持因素,即门静脉血流的增加。IHVR的增加由结构性因素和功能性因素两方面因素导致。其中,肝纤维化、再生结节形成及肝窦重构等是导致肝硬化IHVR增加的重要的结构性因素,而肝窦重构最显著的特点是“肝窦毛细血管化”。肝硬化最明显的特点是过多细胞外基质（extracellular matrix,ECM）在肝内异常沉积,一方面通过瘢痕、再生结节形成及纤维结缔组织增生,使肝内解剖结...
【文章来源】：山东大学山东省211工程院校985工程院校教育部直属院校
【文章页数】：138 页
【学位级别】：博士
【部分图文】：
图１－２卡维地洛改善了?ＣＣ１４诱导的大鼠肝内结构紊乱
?Ｊ??■ＨＵ??图１－２卡维地洛改善了?ＣＣ１４诱导的大鼠肝内结构紊乱。Ａ：各组大鼠的肝脏组??织切片ＨＥ染色（４０Ｘ?）。Ｂ：各组大鼠的肝脏组织切片ＨＥ染色（１００Ｘ?）。（ＣＡＲＶ，??ｃａｒｖｅｄｉｌｏｌ?；?ＣＣＩ４，?ｃａｒｂｏｎ?ｔｅｔｒａｃｈｌｏｒｉｄｅ）。??３９??
Ｃｏｎｔｒｏｌ?ＣＣＵ?ＣＣＵ＾ＣＡＲＶ??图１－４卡维地洛抑制ＣＣＵ诱导的大鼠的ＨＳＣｓ活化。Ａ：各组大鼠的肝脏组织切??片ａ－ＳＭＡＩＨＣ染色（４０Ｘ）。Ｂ：各组大鼠肝脏组织切片ａ－ＳＭＡＩＨＣ染色（１００??Ｘ?）。Ｃ：各组大鼠的肝脏组织中ａ－ＳＭＡ蛋白表达。（ｎ＝６－７，?＃尸＜?０．０１?ｖｓ对照组，??＊＊Ｐ＜?０．０１?ｖｓ?肝硬化组；ＣＡＲＶ，ｃａｒｖｅｄｉｌｏｌ；?ＣＣＩ４，?ｃａｒｂｏｎ?ｔｅｔｒａｃｈｌｏｒｉｄｅ）。????Ｃｏｎｔｒｏｌ?ＣＣＩ４?ＣＣＩ４＋ＣＡＲＶ??ｍｍｍ??图１－５卡维地洛改善ＣＣＵ诱导的大鼠的肝窦毛细血管化。ＴＥＭ观察各组大鼠肝??脏ＬＥＳＣｓ下ＥＣＭ的沉积。（放大倍数１５０００Ｘ?；红色箭头所指为窦周隙；ＣＡＲＶ，??ｃａｒｖｅｄｉｌｏｌ；?ＣＣＩ４，?ｃａｒｂｏｎ?ｔｅｔｒａｃｈｌｏｒｉｄｅ?）。??４１??
【参考文献】：
期刊论文
[1]Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets[J]. Chong-Yang Zhang,Wei-Gang Yuan,Pei He,Jia-Hui Lei,Chun-Xu Wang. World Journal of Gastroenterology. 2016(48)
[2]Carvedilol may attenuate liver cirrhosis by inhibiting angiogenesis through the VEGF-Src-ERK signaling pathway[J]. Qian Ding,Xiang-Guo Tian,Yan Li,Qi-Zhi Wang,Chun-Qing Zhang. World Journal of Gastroenterology. 2015(32)
[3]Cellular and molecular mechanisms in the pathogenesis of liver fibrosis:An update[J]. Gülsüm ?zlem Elpek. World Journal of Gastroenterology. 2014(23)
[4]Paclitaxel ameliorates fibrosis in hepatic stellate cells via inhibition of TGF-β/Smad activity[J]. Jun Zhou, De-Wu Zhong, Qun-Wei Wang, Xiong-Ying Miao, Xun-Di Xu, Department of Hepatobiliary Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China. World Journal of Gastroenterology. 2010(26)
[5]Vascular endothelial growth factor attenuates hepatic sinusoidal capillarization in thioacetamide-induced cirrhotic rats[J]. Hao Xu, Bao-Min Shi, Xiao-Fei Lu, Feng Liang, Tai-Huang Wu, Jian Xu, Department of Hepatobiliary and Pancreas Surgery, Shandong Provincial Hospital, Clinical College of Shandong University, Jinan 250021, Shandong Province, China Hao Xu, Xing Jin, Department of Vascular Surgery, Shandong Provincial Hospital, Clinical College of Shandong University, Jinan 250021, Shandong Province, China. World Journal of Gastroenterology. 2008(15)
[6]Animal models of portal hypertension[J]. Juan G Abraldes,Marcos Pasarín,Juan Carlos García-Pagán. World Journal of Gastroenterology. 2006(41)
本文编号：3624928
【文章来源】：山东大学山东省211工程院校985工程院校教育部直属院校
【文章页数】：138 页
【学位级别】：博士
【部分图文】：
图１－２卡维地洛改善了?ＣＣ１４诱导的大鼠肝内结构紊乱
?Ｊ??■ＨＵ??图１－２卡维地洛改善了?ＣＣ１４诱导的大鼠肝内结构紊乱。Ａ：各组大鼠的肝脏组??织切片ＨＥ染色（４０Ｘ?）。Ｂ：各组大鼠的肝脏组织切片ＨＥ染色（１００Ｘ?）。（ＣＡＲＶ，??ｃａｒｖｅｄｉｌｏｌ?；?ＣＣＩ４，?ｃａｒｂｏｎ?ｔｅｔｒａｃｈｌｏｒｉｄｅ）。??３９??
Ｃｏｎｔｒｏｌ?ＣＣＵ?ＣＣＵ＾ＣＡＲＶ??图１－４卡维地洛抑制ＣＣＵ诱导的大鼠的ＨＳＣｓ活化。Ａ：各组大鼠的肝脏组织切??片ａ－ＳＭＡＩＨＣ染色（４０Ｘ）。Ｂ：各组大鼠肝脏组织切片ａ－ＳＭＡＩＨＣ染色（１００??Ｘ?）。Ｃ：各组大鼠的肝脏组织中ａ－ＳＭＡ蛋白表达。（ｎ＝６－７，?＃尸＜?０．０１?ｖｓ对照组，??＊＊Ｐ＜?０．０１?ｖｓ?肝硬化组；ＣＡＲＶ，ｃａｒｖｅｄｉｌｏｌ；?ＣＣＩ４，?ｃａｒｂｏｎ?ｔｅｔｒａｃｈｌｏｒｉｄｅ）。????Ｃｏｎｔｒｏｌ?ＣＣＩ４?ＣＣＩ４＋ＣＡＲＶ??ｍｍｍ??图１－５卡维地洛改善ＣＣＵ诱导的大鼠的肝窦毛细血管化。ＴＥＭ观察各组大鼠肝??脏ＬＥＳＣｓ下ＥＣＭ的沉积。（放大倍数１５０００Ｘ?；红色箭头所指为窦周隙；ＣＡＲＶ，??ｃａｒｖｅｄｉｌｏｌ；?ＣＣＩ４，?ｃａｒｂｏｎ?ｔｅｔｒａｃｈｌｏｒｉｄｅ?）。??４１??
【参考文献】：
期刊论文
[1]Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets[J]. Chong-Yang Zhang,Wei-Gang Yuan,Pei He,Jia-Hui Lei,Chun-Xu Wang. World Journal of Gastroenterology. 2016(48)
[2]Carvedilol may attenuate liver cirrhosis by inhibiting angiogenesis through the VEGF-Src-ERK signaling pathway[J]. Qian Ding,Xiang-Guo Tian,Yan Li,Qi-Zhi Wang,Chun-Qing Zhang. World Journal of Gastroenterology. 2015(32)
[3]Cellular and molecular mechanisms in the pathogenesis of liver fibrosis:An update[J]. Gülsüm ?zlem Elpek. World Journal of Gastroenterology. 2014(23)
[4]Paclitaxel ameliorates fibrosis in hepatic stellate cells via inhibition of TGF-β/Smad activity[J]. Jun Zhou, De-Wu Zhong, Qun-Wei Wang, Xiong-Ying Miao, Xun-Di Xu, Department of Hepatobiliary Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China. World Journal of Gastroenterology. 2010(26)
[5]Vascular endothelial growth factor attenuates hepatic sinusoidal capillarization in thioacetamide-induced cirrhotic rats[J]. Hao Xu, Bao-Min Shi, Xiao-Fei Lu, Feng Liang, Tai-Huang Wu, Jian Xu, Department of Hepatobiliary and Pancreas Surgery, Shandong Provincial Hospital, Clinical College of Shandong University, Jinan 250021, Shandong Province, China Hao Xu, Xing Jin, Department of Vascular Surgery, Shandong Provincial Hospital, Clinical College of Shandong University, Jinan 250021, Shandong Province, China. World Journal of Gastroenterology. 2008(15)
[6]Animal models of portal hypertension[J]. Juan G Abraldes,Marcos Pasarín,Juan Carlos García-Pagán. World Journal of Gastroenterology. 2006(41)
本文编号：3624928
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