The two most widely used experimental models of advanced liver disease are the administration of carbon tetrachloride, and common bile duct ligation (BDL), however, neither has been systematically evaluated as a model...The two most widely used experimental models of advanced liver disease are the administration of carbon tetrachloride, and common bile duct ligation (BDL), however, neither has been systematically evaluated as a model of hepatorenal syndrome (HRS). The BDL model in rats, studied at diverse time points, induced a progressive renal dysfunction without structural changes in the kidney. The authors concluded that BDL is a good model for further studies of HRS and its treatment. However, the renal impairment observed at the acute phase of the BDL model is based on a different pathophysiology than that of HRS. Specifi cally, in acute obstructive jaundice, cholemia predominates over parenchymal liver disease (reversible at this stage without portal hypertension or cirrhosis) and independently induces negative inotropic and chronotropic effects on the heart, impaired sympathetic vasoconstriction response and profound natriuresis and diuresis that might lead to volume depletion. In addition, systemic endotoxemia contributes to the prerenal etiology of renal impairment and promotes direct nephrotoxicity and acute tubular necrosis. On the other hand, the renal failure observed in the chronic BDL model (with development of biliary cirrhosis, portal hypertension and ascites) shares pathophysiological similarities with HRS, but the accordance of the chronic BDL model to the diagnostic criteria of HRS (e.g. absence of spontaneous bacterial peritonitis, no renal function improvement after plasma volume expansion) should have been confirmed. In conclusion, we think that the BDL model is not suitable for the study of the natural history of HRS, but the chronic BDL model might be valid for the study of established HRS and its potential therapies.展开更多
AIM： To analyze the polygraphic sleep patterns during cirrhosis progression in a rat model by repeated CCh administration. METHODS： Male Wistar rats received three weekly injections of CCl4 for 11 wk, and were analy...AIM： To analyze the polygraphic sleep patterns during cirrhosis progression in a rat model by repeated CCh administration. METHODS： Male Wistar rats received three weekly injections of CCl4 for 11 wk, and were analyzed before and during the induction of cirrhosis. Rats were im- planted with electrodes to record their sleep patterns. Polygraph recordings were made weekly over 11 wk for 8 h, during the light period. After a basal recording, rats received three weekly injections of CCl4. Histological confirmation of cirrhosis was performed after 11 wk. RESULTS： The results showed a progressive decrease in total wake time that reached statistical significance from the second week of treatment. In addition, there was an increase in total time of slow wave sleep （SWS）Ⅱ and rapid eye movement sleep （REM sleep） in most of the 11 wk. SWS I showed no significant variations. During the final weeks, a significant increase in REM sleep frequency was also observed. Histological analyses of the livers showed unequivocal signs of cirrhosis. CONCLUSION： These data suggest that hepatic failure produced by CCh administration is capable of modifying the sleep pattern even after only a few doses.展开更多
OBJECTIVE：To determine the effects of human umbilical cord mesenchymal stem cell （UCMSC） transplantation, alone or in combination with tanshi- none IIA （Tan ⅡA） on hepatic cirrhosis in rats. METHODS： A rat mode...OBJECTIVE：To determine the effects of human umbilical cord mesenchymal stem cell （UCMSC） transplantation, alone or in combination with tanshi- none IIA （Tan ⅡA） on hepatic cirrhosis in rats. METHODS： A rat model of cirrhosis was established. Rats were divided into control, UCMSC, and UCSMC plus Tan IIA groups. Rats in the UCMSC group were injected via the tail vein with 0.2 mL Dil-labeled UCMSC suspension. Intraperitoneal Tan ⅡA injections （20 mg/kg） were started on the day of UCMSC transplantation in the UCMSC plus Tan IIA group, and continued for 7 consecutive days thereafter. Rats were sacrificed 1 day, 3 days, 1 month, and 3 months after transplantation and the numbers of Dil-labeled UCMSCs colonizing the liver were determined. Albumin （ALB） and alanine aminotransferase （ALT） levels were measured in venous blood, and mRNA and protein expression lev- els of human ALB and cytokeratin （CK）-18 in liver tissues were determined by reverse transcrip- tion-polymerase chain reaction and western blotting, respectively.RESULTS： Serum ALT levels were significantly lower and serum ALB levels significantly higher in rats in the UCMSC group compared with the control group （P 〈 0.05）. Hepatic CK-18 and ALB mRNA and protein expression levels increased after transplantation, and were significantly higher in the UCMSC plus Tan ⅡA group compared with the UCMSC group （P 〈 0.05）.CONCLUSION： Human UCMSCs transplanted into rats with liver cirrhosis can grow and differentiate into hepatocyte-like cells resulting in improved liver function in vivo. Tan ⅡA further influenced transplantation outcomes.展开更多
文摘The two most widely used experimental models of advanced liver disease are the administration of carbon tetrachloride, and common bile duct ligation (BDL), however, neither has been systematically evaluated as a model of hepatorenal syndrome (HRS). The BDL model in rats, studied at diverse time points, induced a progressive renal dysfunction without structural changes in the kidney. The authors concluded that BDL is a good model for further studies of HRS and its treatment. However, the renal impairment observed at the acute phase of the BDL model is based on a different pathophysiology than that of HRS. Specifi cally, in acute obstructive jaundice, cholemia predominates over parenchymal liver disease (reversible at this stage without portal hypertension or cirrhosis) and independently induces negative inotropic and chronotropic effects on the heart, impaired sympathetic vasoconstriction response and profound natriuresis and diuresis that might lead to volume depletion. In addition, systemic endotoxemia contributes to the prerenal etiology of renal impairment and promotes direct nephrotoxicity and acute tubular necrosis. On the other hand, the renal failure observed in the chronic BDL model (with development of biliary cirrhosis, portal hypertension and ascites) shares pathophysiological similarities with HRS, but the accordance of the chronic BDL model to the diagnostic criteria of HRS (e.g. absence of spontaneous bacterial peritonitis, no renal function improvement after plasma volume expansion) should have been confirmed. In conclusion, we think that the BDL model is not suitable for the study of the natural history of HRS, but the chronic BDL model might be valid for the study of established HRS and its potential therapies.
基金Supported by Grant 50633 from CONACyT to Jiménez-Anguiano A
文摘AIM： To analyze the polygraphic sleep patterns during cirrhosis progression in a rat model by repeated CCh administration. METHODS： Male Wistar rats received three weekly injections of CCl4 for 11 wk, and were analyzed before and during the induction of cirrhosis. Rats were im- planted with electrodes to record their sleep patterns. Polygraph recordings were made weekly over 11 wk for 8 h, during the light period. After a basal recording, rats received three weekly injections of CCl4. Histological confirmation of cirrhosis was performed after 11 wk. RESULTS： The results showed a progressive decrease in total wake time that reached statistical significance from the second week of treatment. In addition, there was an increase in total time of slow wave sleep （SWS）Ⅱ and rapid eye movement sleep （REM sleep） in most of the 11 wk. SWS I showed no significant variations. During the final weeks, a significant increase in REM sleep frequency was also observed. Histological analyses of the livers showed unequivocal signs of cirrhosis. CONCLUSION： These data suggest that hepatic failure produced by CCh administration is capable of modifying the sleep pattern even after only a few doses.
基金Supported by Medical Science Research Project,Department of Health of Jiangsu Province(No.H201007)the Natural Science Foundation of Jiangsu Province(No.BK2012481)
文摘OBJECTIVE：To determine the effects of human umbilical cord mesenchymal stem cell （UCMSC） transplantation, alone or in combination with tanshi- none IIA （Tan ⅡA） on hepatic cirrhosis in rats. METHODS： A rat model of cirrhosis was established. Rats were divided into control, UCMSC, and UCSMC plus Tan IIA groups. Rats in the UCMSC group were injected via the tail vein with 0.2 mL Dil-labeled UCMSC suspension. Intraperitoneal Tan ⅡA injections （20 mg/kg） were started on the day of UCMSC transplantation in the UCMSC plus Tan IIA group, and continued for 7 consecutive days thereafter. Rats were sacrificed 1 day, 3 days, 1 month, and 3 months after transplantation and the numbers of Dil-labeled UCMSCs colonizing the liver were determined. Albumin （ALB） and alanine aminotransferase （ALT） levels were measured in venous blood, and mRNA and protein expression lev- els of human ALB and cytokeratin （CK）-18 in liver tissues were determined by reverse transcrip- tion-polymerase chain reaction and western blotting, respectively.RESULTS： Serum ALT levels were significantly lower and serum ALB levels significantly higher in rats in the UCMSC group compared with the control group （P 〈 0.05）. Hepatic CK-18 and ALB mRNA and protein expression levels increased after transplantation, and were significantly higher in the UCMSC plus Tan ⅡA group compared with the UCMSC group （P 〈 0.05）.CONCLUSION： Human UCMSCs transplanted into rats with liver cirrhosis can grow and differentiate into hepatocyte-like cells resulting in improved liver function in vivo. Tan ⅡA further influenced transplantation outcomes.
