Cirrhosis caused by multiple etiologies can lead to portal hypertension. The prognosis of patients with portal hypertension in decompensated cirrhosis is significantly poor. Disorders in the patient′s internal environment caused by various complications often evolve into organ failure both inside and outside the liver. For cirrhosis caused by different etiologies, there are still some relief drugs used in the early stages, but the mechanism of disease progression in patients with decompensated cirrhosis and portal hypertension is currently unclear, and there is a lack of effective treatment plans for disease progression. Therefore, revealing the pathophysiological mechanisms of decompensated cirrhosis with portal hypertension and seeking effective drug targets for treating this disease have become the focus of current research. This article summarizes the pathological and physiological changes of intrahepatic and extrahepatic organ failure during the decompensated phase of liver cirrhosis, and briefly describes the cellular and molecular regulatory mechanisms related to intrahepatic vascular resistance, portal system, cardiovascular system, and inflammatory mediators. By comprehensively analyzing the pathological and physiological development process of decompensated cirrhosis with portal hypertension, the potential cellular and molecular mechanisms that cause disease deterioration or remission can be better understood, which can help improve the accuracy of disease diagnosis and the correct grasp of disease staging. In addition, identifying drug treatment targets to block the progression of the disease will guide clinical staff to better cope with refractory portal hypertension, and even improve the prognosis of patients.
FAN Qiang, WU Guangbo, ZHAO Jinbo, ZHENG Lei, LUO Meng. Research progress in pathophysiological and molecular mechanism changes during decompensated phase of portal hypertension in liver cirrhosis. Journal of Shanghai Jiao Tong University (Medical Science)[J], 2024, 44(3): 379-384 doi:10.3969/j.issn.1674-8115.2024.03.011
一氧化氮（NO）等内源性血管扩张剂的减少与血管收缩剂（去甲肾上腺素、血管紧张素Ⅱ、内皮素和血栓素A2）增加引起的平衡失调也是肝内血管阻力增加的重要因素［7］。研究［13-15］表明，某些药物如索拉唑嗪可扩张肝内血管，但因其不良反应而无法单独应用于临床；另有他汀类药物和环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）激活剂可通过过表达转录因子Krüppel样因子2上调NO的肝内释放；该转录因子亦被报道可调控多种血管保护基因。同时，他汀类药物可抑制Ras同源基因家族成员A（RAS homologous gene family member A，RhoA）-Rho激酶（可激活HSC并引起其收缩功能）的激活，有助于降低肝内阻力［16-17］。他汀类药物还具有抗炎和抗纤维化作用，在缓解肝内结构成分的病理性改变方面也起着重要作用［18］。
FAN Qiang and WU Guangbo participated in the literature search, manuscript writing and revision. ZHAO Jinbo participated in the revision of the manuscript format. ZHENG Lei and LUO Meng participated in the design and revision of the manuscript, and proposed modification suggestion. All the authors have read the last version of paper and agreed for the submission.
利益冲突声明
所有作者声明不存在利益冲突。
COMPETING INTERESTS
All authors disclose no relevant conflict of interests.
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... 一氧化氮（NO）等内源性血管扩张剂的减少与血管收缩剂（去甲肾上腺素、血管紧张素Ⅱ、内皮素和血栓素A2）增加引起的平衡失调也是肝内血管阻力增加的重要因素［7］.研究［13-15］表明，某些药物如索拉唑嗪可扩张肝内血管，但因其不良反应而无法单独应用于临床；另有他汀类药物和环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）激活剂可通过过表达转录因子Krüppel样因子2上调NO的肝内释放；该转录因子亦被报道可调控多种血管保护基因.同时，他汀类药物可抑制Ras同源基因家族成员A（RAS homologous gene family member A，RhoA）-Rho激酶（可激活HSC并引起其收缩功能）的激活，有助于降低肝内阻力［16-17］.他汀类药物还具有抗炎和抗纤维化作用，在缓解肝内结构成分的病理性改变方面也起着重要作用［18］. ...
... 一氧化氮（NO）等内源性血管扩张剂的减少与血管收缩剂（去甲肾上腺素、血管紧张素Ⅱ、内皮素和血栓素A2）增加引起的平衡失调也是肝内血管阻力增加的重要因素［7］.研究［13-15］表明，某些药物如索拉唑嗪可扩张肝内血管，但因其不良反应而无法单独应用于临床；另有他汀类药物和环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）激活剂可通过过表达转录因子Krüppel样因子2上调NO的肝内释放；该转录因子亦被报道可调控多种血管保护基因.同时，他汀类药物可抑制Ras同源基因家族成员A（RAS homologous gene family member A，RhoA）-Rho激酶（可激活HSC并引起其收缩功能）的激活，有助于降低肝内阻力［16-17］.他汀类药物还具有抗炎和抗纤维化作用，在缓解肝内结构成分的病理性改变方面也起着重要作用［18］. ...
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... 一氧化氮（NO）等内源性血管扩张剂的减少与血管收缩剂（去甲肾上腺素、血管紧张素Ⅱ、内皮素和血栓素A2）增加引起的平衡失调也是肝内血管阻力增加的重要因素［7］.研究［13-15］表明，某些药物如索拉唑嗪可扩张肝内血管，但因其不良反应而无法单独应用于临床；另有他汀类药物和环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）激活剂可通过过表达转录因子Krüppel样因子2上调NO的肝内释放；该转录因子亦被报道可调控多种血管保护基因.同时，他汀类药物可抑制Ras同源基因家族成员A（RAS homologous gene family member A，RhoA）-Rho激酶（可激活HSC并引起其收缩功能）的激活，有助于降低肝内阻力［16-17］.他汀类药物还具有抗炎和抗纤维化作用，在缓解肝内结构成分的病理性改变方面也起着重要作用［18］. ...
1
... 一氧化氮（NO）等内源性血管扩张剂的减少与血管收缩剂（去甲肾上腺素、血管紧张素Ⅱ、内皮素和血栓素A2）增加引起的平衡失调也是肝内血管阻力增加的重要因素［7］.研究［13-15］表明，某些药物如索拉唑嗪可扩张肝内血管，但因其不良反应而无法单独应用于临床；另有他汀类药物和环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）激活剂可通过过表达转录因子Krüppel样因子2上调NO的肝内释放；该转录因子亦被报道可调控多种血管保护基因.同时，他汀类药物可抑制Ras同源基因家族成员A（RAS homologous gene family member A，RhoA）-Rho激酶（可激活HSC并引起其收缩功能）的激活，有助于降低肝内阻力［16-17］.他汀类药物还具有抗炎和抗纤维化作用，在缓解肝内结构成分的病理性改变方面也起着重要作用［18］. ...
1
... 一氧化氮（NO）等内源性血管扩张剂的减少与血管收缩剂（去甲肾上腺素、血管紧张素Ⅱ、内皮素和血栓素A2）增加引起的平衡失调也是肝内血管阻力增加的重要因素［7］.研究［13-15］表明，某些药物如索拉唑嗪可扩张肝内血管，但因其不良反应而无法单独应用于临床；另有他汀类药物和环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）激活剂可通过过表达转录因子Krüppel样因子2上调NO的肝内释放；该转录因子亦被报道可调控多种血管保护基因.同时，他汀类药物可抑制Ras同源基因家族成员A（RAS homologous gene family member A，RhoA）-Rho激酶（可激活HSC并引起其收缩功能）的激活，有助于降低肝内阻力［16-17］.他汀类药物还具有抗炎和抗纤维化作用，在缓解肝内结构成分的病理性改变方面也起着重要作用［18］. ...
1
... 一氧化氮（NO）等内源性血管扩张剂的减少与血管收缩剂（去甲肾上腺素、血管紧张素Ⅱ、内皮素和血栓素A2）增加引起的平衡失调也是肝内血管阻力增加的重要因素［7］.研究［13-15］表明，某些药物如索拉唑嗪可扩张肝内血管，但因其不良反应而无法单独应用于临床；另有他汀类药物和环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）激活剂可通过过表达转录因子Krüppel样因子2上调NO的肝内释放；该转录因子亦被报道可调控多种血管保护基因.同时，他汀类药物可抑制Ras同源基因家族成员A（RAS homologous gene family member A，RhoA）-Rho激酶（可激活HSC并引起其收缩功能）的激活，有助于降低肝内阻力［16-17］.他汀类药物还具有抗炎和抗纤维化作用，在缓解肝内结构成分的病理性改变方面也起着重要作用［18］. ...
