AIM: To investigate the role of tolvaptan in regulating aquaporin(AQP)-2 expression and fecal water content in cirrhotic rats with ascites.METHODS: Cirrhosis with ascites was induced in rats by repetitive dorsal injec...AIM: To investigate the role of tolvaptan in regulating aquaporin(AQP)-2 expression and fecal water content in cirrhotic rats with ascites.METHODS: Cirrhosis with ascites was induced in rats by repetitive dorsal injection of CCl4 for 14 wk. In total, 84 cirrhotic rats with ascites divided into three groups(vehicle, 3 mg/kg and 5 mg/kg tolvaptan), and then further divided into five subgroups(days 1, 2, 3, 4, and 5). Blood samples were obtained to measure vasopressin and sodium concentrations. Rats were killed and colonic mucosa was scraped for analysis of protein expression and AQP-2 transcriptional level. The whole layer was fixed for hematoxylin&eosin(HE) staining and feces were collected for determination of fecal water content. CONCLUSION: Compared with vehicle, vasopressin decreased significantly in the tolvaptan groups from day 2 to a similar level in each treatment group. AQP-2 showed significant upregulation in cirrhotic rats with ascites compared with an untreated control group(100% ± 22.9% vs 22.2% ± 10.23%, P < 0.01). After administration of tolvaptan, AQP-2 expression began to decrease significantly from day 2 in each treatment group, but no significant difference was finally found between the treatment groups. Fecal water content inthe distal colon was increased by 5 mg/kg tolvaptan on day 1(66.8% ± 9.3% vs 41.4% ± 6.3%, in the vehicle group, P < 0.05). Fecal water content returned to baseline at day 4 at the latest in both treatment groups, and did not correspond to the change in AQP-2 expression. HE staining of the colonic mucosa showed no mucosal damage related to tolvaptan.CONCLUSION: Upregulation of AQP-2 in the distal colon is found in cirrhotic rats with ascites. Tolvaptan inhibits its expression and may decrease water reabsorption and induce diarrhea.展开更多
In current study, the effect of angiotensin receptor blocker Micardis on the localization and expression of aquaporin-2 （AQP2） was investigated in the renal medullary collecting duct of mice with diabetic nephropat...In current study, the effect of angiotensin receptor blocker Micardis on the localization and expression of aquaporin-2 （AQP2） was investigated in the renal medullary collecting duct of mice with diabetic nephropathy （DN）. Mice were divided into three groups： normal group, DN group and Micardis-treated group. Six weeks after establishment of STZ-induced DN model in mice, the expression of AQP2 in renal medulla was detected measured by semiquantitative immunofluorescence histochemistry and Western blot techniques, and the localization of AQP2 by confocal immunofluorescence laser scanning microscopy. The results showed that the urinary osmolality was decreased in DN group as compared with normal group （2.39±0.11 vs 3.16±0.16, P〈0.05）. Although the localization of AQP2 on the renal medulla was unchanged, the expression of AQP2 was increased significantly in DN group as compared with normal group. Micardis could partly attenuate above changes. It was concluded that treatment with Micardis could partly rectify the abnormal expression of AQP2 in renal medulla of DN mice, which suggested that rennin-angiotensin system （RAS） is implicated in the pathogenesis of DN by regulating the expression of AQP2.展开更多
文摘AIM: To investigate the role of tolvaptan in regulating aquaporin(AQP)-2 expression and fecal water content in cirrhotic rats with ascites.METHODS: Cirrhosis with ascites was induced in rats by repetitive dorsal injection of CCl4 for 14 wk. In total, 84 cirrhotic rats with ascites divided into three groups(vehicle, 3 mg/kg and 5 mg/kg tolvaptan), and then further divided into five subgroups(days 1, 2, 3, 4, and 5). Blood samples were obtained to measure vasopressin and sodium concentrations. Rats were killed and colonic mucosa was scraped for analysis of protein expression and AQP-2 transcriptional level. The whole layer was fixed for hematoxylin&eosin(HE) staining and feces were collected for determination of fecal water content. CONCLUSION: Compared with vehicle, vasopressin decreased significantly in the tolvaptan groups from day 2 to a similar level in each treatment group. AQP-2 showed significant upregulation in cirrhotic rats with ascites compared with an untreated control group(100% ± 22.9% vs 22.2% ± 10.23%, P < 0.01). After administration of tolvaptan, AQP-2 expression began to decrease significantly from day 2 in each treatment group, but no significant difference was finally found between the treatment groups. Fecal water content inthe distal colon was increased by 5 mg/kg tolvaptan on day 1(66.8% ± 9.3% vs 41.4% ± 6.3%, in the vehicle group, P < 0.05). Fecal water content returned to baseline at day 4 at the latest in both treatment groups, and did not correspond to the change in AQP-2 expression. HE staining of the colonic mucosa showed no mucosal damage related to tolvaptan.CONCLUSION: Upregulation of AQP-2 in the distal colon is found in cirrhotic rats with ascites. Tolvaptan inhibits its expression and may decrease water reabsorption and induce diarrhea.
基金the Scientific Research Foundation for the Returned Overseas Chinese Scholars,Ministry of Education of China (Grant No. 2007-1108)
文摘In current study, the effect of angiotensin receptor blocker Micardis on the localization and expression of aquaporin-2 （AQP2） was investigated in the renal medullary collecting duct of mice with diabetic nephropathy （DN）. Mice were divided into three groups： normal group, DN group and Micardis-treated group. Six weeks after establishment of STZ-induced DN model in mice, the expression of AQP2 in renal medulla was detected measured by semiquantitative immunofluorescence histochemistry and Western blot techniques, and the localization of AQP2 by confocal immunofluorescence laser scanning microscopy. The results showed that the urinary osmolality was decreased in DN group as compared with normal group （2.39±0.11 vs 3.16±0.16, P〈0.05）. Although the localization of AQP2 on the renal medulla was unchanged, the expression of AQP2 was increased significantly in DN group as compared with normal group. Micardis could partly attenuate above changes. It was concluded that treatment with Micardis could partly rectify the abnormal expression of AQP2 in renal medulla of DN mice, which suggested that rennin-angiotensin system （RAS） is implicated in the pathogenesis of DN by regulating the expression of AQP2.
