Effects of vasopressin on gene expression in rat inner ear.

Vasopressin regulates water excretion from the kidney by increasing water permeability of the collecting duct as a hormone secreted from the posterior pituitary. A clinical study reported that plasma levels of arginine vasopressin were significantly higher in patients suffering from Meniere's disease. It was histologically confirmed that chronic administration of vasopressin induced endolymphatic hydrops in guinea pigs. However, the mechanism of endolymphatic hydrops induced by vasopressin is still unclear. We use cDNA microarray to study the effects of vasopressin on gene expression profiles in rat inner ear to elucidate the possible mechanism of the induced hydrolabyrinth. Wistar rats were intraperitoneally injected with 50 microg/kg arginine vasopressin once a day for one week. Hydrolabyrinth in rat inner ear induced by administration of vasopressin was detected by HE stain. The bullae were dissected out for total RNA extraction. cDNAs were synthesized by reverse transcription and labeled with Cyanine3 (Cy3) or Cyanine5 (Cy5). The BiostarR-40s cDNA microarray was hybridized with the above cDNAs and the changes of mRNA expression intensity were showed by data analysis. Furthermore, the changes of aquaporins expression level were measured by reverse transcription polymerase chain (RT-PCR). Endolymphatic hydrops were present in rats intraperitoneally injected with vasopressin. 226 known differentially expressed genes were screened out in rat inner ear induced by vasopressin injection. Of the 226 genes, 18 transcripts were increased by 5-fold or more, and 7 transcripts were decreased to 0.2-fold or less. Ten differentially expressed genes were identified that associate with cell signal transduction, 14 differentially expressed genes were identified that relate to ion transport, 7 differentially expressed genes were involved in vesicle-mediated transport, and 2 differentially expressed genes were aquaporin 2 (AQP2) and aquaporin 7 (AQP7). The expression level of AQP2 was significantly higher and AQP7 was significantly lower. These results suggest that there are obvious differences in gene expression profiles in inner ear between vasopressin injected rats and normal control rats. Vasopressin may disturb fluid homeostasis in inner ear by way of signal transduction, ion transport, vesicle-mediated transport and aquaporins. It is likely that up-regulated expression of AQP2 mRNA and down-regulated expression of AQP7 mRNA in the rat inner ear caused by vasopressin induce an increased production and a decreased absorption of endolymph, resulting in endolymphatic hydrops.

Changes in serum and histology of patients with chronic hepatitis B after interferon alpha-2b treatment.

AIM: Chronic hepatitis B is a serious health problem. Interferon has long been used to treat Chronic hepatitis B. To evaluate the effects of interferon on chronic hepatitis B better, we designed the study to investigate the changes in sera and liver histology of patients with chronic hepatitis B after interferon alpha-2b treatment. METHODS: Twenty-four patients with chronic hepatitis B were enrolled in this study. They all received interferon alpha-2b treatment as following: 3 million units, i.m. t.i.w., for 18 weeks. Sera of all patients were obtained respectively for evaluation of ALT, HBsAg, HBcAg, HBeAg, HBV DNA and TIMP-1 before and after interferon treatment, also a liver biopsy pre- and post-treatment was performed for comparison of HAI, HBsAg, HBcAg, HBeAg, TIMP-1 and activated HSC in the liver tissue. RESULTS: Patients who had normalization of serum ALT and seroconversion of HBeAg and/or HBV DNA (blot hybridization) after treatment were defined as responders. The response rate in this study group was 37.5 % (7/24). Compared to pretreatment, the serum HBV DNA and TIMP-1 decreased significantly (P<0.05), so did the HAI, HBcAg, HBeAg, TIMP-1 and activated HSC (P<0.05). CONCLUSION: The significant decrease in HBV DNA in sera, the seroconversion of HBeAg, and the decrease of viral expression in liver indicated that interferon alpha-2b treatment can inhibit viral replication. The normalization of ALT in sera and the improvement of HAI in liver showed that interferon alpha-2b can improve the liver histology of patients with chronic hepatitis B. At the same time, interferon alpha-2b treatment can reduce the TIMP-1 in serum and liver and decrease the number of activated HSC, which may alleviate or inhibit hepatic fibrosis. Although the response rate was unsatisfactory, interferon play a beneficial role on patients with chronic hepatitis B in other respects. We still need further studies to improve the therapy effects.