The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely...The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely sensitive to injury.Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage.The primary regulator of intracellular pH in the liver is the Na+/H+exchanger(NHE).Physiologically,NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline.Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensinconverting enzyme 2.In severe cases of coronavirus disease 2019,high angiotensin II levels may cause NHE overstimulation and lipid accumulation in the liver.NHE overstimulation can lead to hepatocyte death.NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver.Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation,the virus may indirectly cause an increase in fibrinogen and D-dimer levels.NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release.Also,NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver.Increasing NHE3 activity leads to Na+loading,which impairs the containment and fluidity of bile acid.NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid,thus triggering systemic damage.Unlike other tissues,tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine.Thus,increased luminal Na+leads to diarrhea and cytokine release.Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver.展开更多
BACKGROUND The effects of prostaglandin E(PGE)combined with continuous renal replacement therapy(CRRT)on renal function and inflammatory responses in patients with septic acute kidney injury(SAKI)remain unclear.AIM To...BACKGROUND The effects of prostaglandin E(PGE)combined with continuous renal replacement therapy(CRRT)on renal function and inflammatory responses in patients with septic acute kidney injury(SAKI)remain unclear.AIM To investigate the effects of PGE combined with CRRT on urinary augmenter of liver regeneration(ALR),urinary Na+/H+exchanger 3(NHE3),and serum inflammatory cytokines in patients with SAKI.METHODS The clinical data of 114 patients with SAKI admitted to Yichang Second People's Hospital from May 2017 to January 2019 were collected.Fifty-three cases treated by CRRT alone were included in a control group,while the other 61 cases treated with PGE combined with CRRT were included in an experimental group.Their urinary ALR,urinary NHE3,serum inflammatory cytokines,renal function indices,and immune function indices were detected.Changes in disease recovery and the incidence of adverse reactions were observed.The 28-d survival curve was plotted.RESULTS Before treatment,urinary ALR,urinary NHE3,blood urea nitrogen(BUN),serum creatinine(SCr),CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio in the control and experimental groups were approximately the same.After treatment,urinary ALR and NHE3 decreased,while BUN,SCr,CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio increased in all subjects.Urinary ALR,urinary NHE3,BUN,and SCr in the experimental group were significantly lower than those in the control group,while CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio were significantly higher than those in the control group(P<0.05).After treatment,the levels of tumor necrosis factor-α,interleukin-18,and high sensitivity C-reactive protein in the experimental group were significantly lower than those in the control group(P<0.05).The time for urine volume recovery and intensive care unit treatment in the experimental group was significantly shorter than that in the control group(P<0.05),although there was no statistically significant difference in hospital stays between the two groups.The total incidence of adverse reactions did not differ statistically between the two groups.The 28-d survival rate in the experimental group(80.33%)was significantly higher than that in the control group(66.04%).CONCLUSION PGE combined with CRRT is clinically effective for treating SAKI,and the combination therapy can significantly improve renal function and reduce inflammatory responses.展开更多
Background Recent studies showed the central Na＋/H＋ exchanger type 3 （NHE3） has a close relationship with ventilation control.The objective of the study is to investigate the role of NHE3 in sleep apnea in Sprague...Background Recent studies showed the central Na＋/H＋ exchanger type 3 （NHE3） has a close relationship with ventilation control.The objective of the study is to investigate the role of NHE3 in sleep apnea in Sprague-Dawley （SD） rats.Methods A sleep study was performed on 20 male SD rats to analyze the correlation between the sleep apneic events and total NHE3 protein content and inactive NHE3（pS552） in the brainstem measured by Western blotting.Another 20 adult male SD rats received 3 days of sleep and respiration monitoring for 6 hours a day,with adaption on the first day,0.5％ DMSO microinjection into the fourth ventricle on the second day,and AVE0657 （specific inhibitor of NHE3） microinjection on the third day.Rats were divided into two groups with injection of 5 μmol/L or 8 μmol/L AVE0657 before the sleep study.The effects of AVE0657 on sleep apnea and sleep structure of rats were analyzed through self-control.Results The total post-sigh apnea index （TPSAI） and post-sigh apnea index in non-rapid eye movement （NREM） sleep （NPSAI） and total apnea index （AI） in NREM sleep （NAI） were negatively correlated with NHE3（pS552） protein contents in the brainstem （r=-0.534,-0.547 and-0.505,respectively,P＜0.05）.The spontaneous apnea index in REM sleep （RSPAI） was positively correlated with the level of NHE3（pS552） protein expression in the brainstem （r=0.556,P＜0.05）.However,the sleep AI had no relationship with total NHE3 protein.Compared with the blank control and microinjection of 0.5％ DMSO,5 μmol/L AVE0657 significantly reduced the total AI and NPSAI （both P＜0.05） without a significant effect on sleep architecture.In contrast to blank control and microinjection of 0.5％ DMSO,injection of 8 μmol/L AVE0657 significantly reduced the AI and PSAI in NREM and REM sleep （all P＜0.05）.Conclusions The severity of sleep apnea was negatively correlated with central inactive NHE3.A specific inhibitor of NHE3 decreased the sleep AI.Thus,our results indicate that central NHE3 might be a molecular target for sleep apnea treatment,whose inhibitors may be potential therapeutic drugs for sleep apnea.展开更多
文摘The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely sensitive to injury.Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage.The primary regulator of intracellular pH in the liver is the Na+/H+exchanger(NHE).Physiologically,NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline.Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensinconverting enzyme 2.In severe cases of coronavirus disease 2019,high angiotensin II levels may cause NHE overstimulation and lipid accumulation in the liver.NHE overstimulation can lead to hepatocyte death.NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver.Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation,the virus may indirectly cause an increase in fibrinogen and D-dimer levels.NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release.Also,NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver.Increasing NHE3 activity leads to Na+loading,which impairs the containment and fluidity of bile acid.NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid,thus triggering systemic damage.Unlike other tissues,tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine.Thus,increased luminal Na+leads to diarrhea and cytokine release.Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver.
文摘BACKGROUND The effects of prostaglandin E(PGE)combined with continuous renal replacement therapy(CRRT)on renal function and inflammatory responses in patients with septic acute kidney injury(SAKI)remain unclear.AIM To investigate the effects of PGE combined with CRRT on urinary augmenter of liver regeneration(ALR),urinary Na+/H+exchanger 3(NHE3),and serum inflammatory cytokines in patients with SAKI.METHODS The clinical data of 114 patients with SAKI admitted to Yichang Second People's Hospital from May 2017 to January 2019 were collected.Fifty-three cases treated by CRRT alone were included in a control group,while the other 61 cases treated with PGE combined with CRRT were included in an experimental group.Their urinary ALR,urinary NHE3,serum inflammatory cytokines,renal function indices,and immune function indices were detected.Changes in disease recovery and the incidence of adverse reactions were observed.The 28-d survival curve was plotted.RESULTS Before treatment,urinary ALR,urinary NHE3,blood urea nitrogen(BUN),serum creatinine(SCr),CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio in the control and experimental groups were approximately the same.After treatment,urinary ALR and NHE3 decreased,while BUN,SCr,CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio increased in all subjects.Urinary ALR,urinary NHE3,BUN,and SCr in the experimental group were significantly lower than those in the control group,while CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio were significantly higher than those in the control group(P<0.05).After treatment,the levels of tumor necrosis factor-α,interleukin-18,and high sensitivity C-reactive protein in the experimental group were significantly lower than those in the control group(P<0.05).The time for urine volume recovery and intensive care unit treatment in the experimental group was significantly shorter than that in the control group(P<0.05),although there was no statistically significant difference in hospital stays between the two groups.The total incidence of adverse reactions did not differ statistically between the two groups.The 28-d survival rate in the experimental group(80.33%)was significantly higher than that in the control group(66.04%).CONCLUSION PGE combined with CRRT is clinically effective for treating SAKI,and the combination therapy can significantly improve renal function and reduce inflammatory responses.
基金This work was supported bygrants from the National Natural Science Foundation of China （No. 30900646） and the National Science Foundation of China （No. 81241004）. Conflict of interest： None.
文摘Background Recent studies showed the central Na＋/H＋ exchanger type 3 （NHE3） has a close relationship with ventilation control.The objective of the study is to investigate the role of NHE3 in sleep apnea in Sprague-Dawley （SD） rats.Methods A sleep study was performed on 20 male SD rats to analyze the correlation between the sleep apneic events and total NHE3 protein content and inactive NHE3（pS552） in the brainstem measured by Western blotting.Another 20 adult male SD rats received 3 days of sleep and respiration monitoring for 6 hours a day,with adaption on the first day,0.5％ DMSO microinjection into the fourth ventricle on the second day,and AVE0657 （specific inhibitor of NHE3） microinjection on the third day.Rats were divided into two groups with injection of 5 μmol/L or 8 μmol/L AVE0657 before the sleep study.The effects of AVE0657 on sleep apnea and sleep structure of rats were analyzed through self-control.Results The total post-sigh apnea index （TPSAI） and post-sigh apnea index in non-rapid eye movement （NREM） sleep （NPSAI） and total apnea index （AI） in NREM sleep （NAI） were negatively correlated with NHE3（pS552） protein contents in the brainstem （r=-0.534,-0.547 and-0.505,respectively,P＜0.05）.The spontaneous apnea index in REM sleep （RSPAI） was positively correlated with the level of NHE3（pS552） protein expression in the brainstem （r=0.556,P＜0.05）.However,the sleep AI had no relationship with total NHE3 protein.Compared with the blank control and microinjection of 0.5％ DMSO,5 μmol/L AVE0657 significantly reduced the total AI and NPSAI （both P＜0.05） without a significant effect on sleep architecture.In contrast to blank control and microinjection of 0.5％ DMSO,injection of 8 μmol/L AVE0657 significantly reduced the AI and PSAI in NREM and REM sleep （all P＜0.05）.Conclusions The severity of sleep apnea was negatively correlated with central inactive NHE3.A specific inhibitor of NHE3 decreased the sleep AI.Thus,our results indicate that central NHE3 might be a molecular target for sleep apnea treatment,whose inhibitors may be potential therapeutic drugs for sleep apnea.
