Background and Aims:Hepatopulmonary syndrome(HPS)is characterized by arterial oxygenation defects due to pulmonary vascular dilation in liver disease.To date,liver transplantation remains the only effective treatment ...Background and Aims:Hepatopulmonary syndrome(HPS)is characterized by arterial oxygenation defects due to pulmonary vascular dilation in liver disease.To date,liver transplantation remains the only effective treatment for HPS.This study aimed to explore the preventative role of baicalein in HPS development.Methods:Sixty male rats were randomly assigned to three groups:sham,common bile duct ligation(CBDL),and baicalein,receiving intraperitoneal injections of baicalein(40 mg·kg^(-1)·d^(-1),diluted in saline)for 21 days.Survival rate,liver and kidney function,and bile acid metabolism levels were evaluated.Liver and lung angiogenesis and hepatic glycogen staining were assessed,and the expression of relevant proteins was evaluated by immunohistochemistry.Results:Baicalein improved survival rates and hypoxemia in rats post-CBDL,reducing angiogenic protein levels and enhancing glucose homeostasis.Compared to the untreated group,baicalein suppressed the expression of vascular endothelial growth factor,placental growth factors,matrix metalloprotease 9 and C-X-C motif chemokine 2,and it increased the expression of glycemic regulatory proteins,including dipeptidyl peptidase-4,sirtuin 1,peroxisome proliferatoractivated receptor gamma co-activator 1α,and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3.Conclusion:Baicalein significantly improves hepatic function and hypoxia in HPS rats by attenuating pathological angiogenesis in the liver and lungs,showing promise as a treatment for HPS.展开更多
Background and Aims:The results of basic research implicate the vascular endothelial growth factor(VEGF)family as a potential target of hepatopulmonary syndrome(HPS).However,the negative results of anti-angiogenetic t...Background and Aims:The results of basic research implicate the vascular endothelial growth factor(VEGF)family as a potential target of hepatopulmonary syndrome(HPS).However,the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS.Therefore,we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies.Methods:Clinically,patients with chronic liver disease from two medical centers were enrolled and examined for HPS.Patients were divided into HPS,intrapulmonary vascular dilation[positive contrast-enhanced echocardiography(CEE)and normal oxygenation]and CEE-negative groups.Baseline information and perioperative clinical data were compared between HPS and non-HPS patients.Serum levels of VEGF family members and their receptors were measured.In parallel,HPS rats were established by common bile duct ligation.Liver,lung and serum samples were collected for the evaluation of pathophysiologic changes,as well as the expression levels of the above factors.Results:In HPS rats,all VEGF family members and their receptors underwent significant changes;however,only soluble VEGFR1(sFlt-1)and the sFlt-1/placental growth factor(PLGF)ratio were changed in almost the same manner as those in HPS patients.Furthermore,through feature selection and internal and external validation,sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients.Conclusions:Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.展开更多
基金supported by the National Science Foundation of China(No.82070630 to BY,No.82100658 to YL)Science Foundation of Chongqing(cstc2019jcyj-msxmX0667 to ZZ)National Key R&D Program of China(No.2018YFC0116702 to BY).
文摘Background and Aims:Hepatopulmonary syndrome(HPS)is characterized by arterial oxygenation defects due to pulmonary vascular dilation in liver disease.To date,liver transplantation remains the only effective treatment for HPS.This study aimed to explore the preventative role of baicalein in HPS development.Methods:Sixty male rats were randomly assigned to three groups:sham,common bile duct ligation(CBDL),and baicalein,receiving intraperitoneal injections of baicalein(40 mg·kg^(-1)·d^(-1),diluted in saline)for 21 days.Survival rate,liver and kidney function,and bile acid metabolism levels were evaluated.Liver and lung angiogenesis and hepatic glycogen staining were assessed,and the expression of relevant proteins was evaluated by immunohistochemistry.Results:Baicalein improved survival rates and hypoxemia in rats post-CBDL,reducing angiogenic protein levels and enhancing glucose homeostasis.Compared to the untreated group,baicalein suppressed the expression of vascular endothelial growth factor,placental growth factors,matrix metalloprotease 9 and C-X-C motif chemokine 2,and it increased the expression of glycemic regulatory proteins,including dipeptidyl peptidase-4,sirtuin 1,peroxisome proliferatoractivated receptor gamma co-activator 1α,and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3.Conclusion:Baicalein significantly improves hepatic function and hypoxia in HPS rats by attenuating pathological angiogenesis in the liver and lungs,showing promise as a treatment for HPS.
基金supported by National Science Foundation of China(No.82070630 from Bin Yi,82100658 from Yu-jie Li and 82170634 from Peng Li)National Key R&D Program of China(No.2018YFC0116702 from Bin Yi)+2 种基金Special support for Chongqing postdoctoral research project in 2020 from Yujie Li,Sichuan science and technology department research projects(2019YFS0221 from Peng Li)Chongqing Science and health joint medical research project(2020FYYX076,from Bin Yi)special support project for improving scientific and technological innovation ability of undergraduate(2021XBK19 from Xian-feng Wu).
文摘Background and Aims:The results of basic research implicate the vascular endothelial growth factor(VEGF)family as a potential target of hepatopulmonary syndrome(HPS).However,the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS.Therefore,we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies.Methods:Clinically,patients with chronic liver disease from two medical centers were enrolled and examined for HPS.Patients were divided into HPS,intrapulmonary vascular dilation[positive contrast-enhanced echocardiography(CEE)and normal oxygenation]and CEE-negative groups.Baseline information and perioperative clinical data were compared between HPS and non-HPS patients.Serum levels of VEGF family members and their receptors were measured.In parallel,HPS rats were established by common bile duct ligation.Liver,lung and serum samples were collected for the evaluation of pathophysiologic changes,as well as the expression levels of the above factors.Results:In HPS rats,all VEGF family members and their receptors underwent significant changes;however,only soluble VEGFR1(sFlt-1)and the sFlt-1/placental growth factor(PLGF)ratio were changed in almost the same manner as those in HPS patients.Furthermore,through feature selection and internal and external validation,sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients.Conclusions:Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.
