ABSTRACT
<p><b>OBJECTIVE</b>To explore the changes in the threshold of auditory brainstem response (ABR) and [Ca(2+)]I and calmodulin (CaM) in cochlear nucleus of newborn mice infected by murine cytomegalovirus (MCMV) in the brain.</p><p><b>METHODS</b>Sixty-nine newborn mice were randomized into model group and control group. The model group (54 mice) was established by intracranial injection with MCMV viral suspension 20 l and the same volume of 0.9% sodium chloride was injected in the control group (15 mice). After 1 month, the ABR was tested in a sound-electric screen environment and the threshold was recorded. Then intracellular free calcium [Ca(2+)]i and the mRNA level of CaM in the cochlear nucleus were assayed by flow cytometry and RT-PCR.</p><p><b>RESULTS</b>Compare to the control group [(64.0 ± 1.3) dBSPL], the threshold of ABR in the model group [(84.5 ± 2.7) dBSPL] was increased (F = 2.789,P = 0.000). Moreover, in the model group the intracellular free calcium [Ca(2+)]i and the mRNA level of CaM in the cochlear nucleus were increased (F = 1.290, P = 0.000; F = 4.252, P = 0.023), and the differences were statistically significant.</p><p><b>CONCLUSIONS</b>The intracranial injection of MCMV can lead to abnormal changes in the threshold of ABR in mice, and the change of [Ca(2+) ]I/CaM in cochlear nucleus may be the important pathological basis of sensorineural hearing loss induced by MCMV infection.</p>
Subject(s)
Animals , Female , Male , Mice , 3T3 Cells , Auditory Threshold , Calcium , Metabolism , Calmodulin , Metabolism , Central Nervous System Viral Diseases , Metabolism , Virology , Cochlear Nucleus , Metabolism , Cytomegalovirus , Cytomegalovirus Infections , Metabolism , Evoked Potentials, Auditory, Brain Stem , Mice, Inbred BALB CABSTRACT
<p><b>OBJECTIVE</b>To explore the influence of histamine H3 receptor agonist, IMETIT and simultaneous use of IMETIT and H1-receptor antagonist, Loratadine, on the symptoms of allergic rhinitis (AR) and substance P(SP) secretion and expression of SP receptor (SP-R) mRNA in AR model in guinea pigs.</p><p><b>METHODS</b>Guinea pigs were divided randomly into 4 groups: AR group (group A), IMETIT group (group B), Loratadine group (group C) and IMETIT+Loratadine group (group D). The severity of AR was assessed by determining the extent of three markers of allergic symptoms (sneezing, nasal rubbing and nose blocking). The changes in the nasal mucosa were studied by pathological methods. The expression of positive cell of SP was detected by immunohistochemistry. SP-R mRNA expression in nasal mucosa was used to do reverse transcriptive-polymerase chain reaction (RT-PCR). Statistical analysis was performed using a SPSS 13.0 software.</p><p><b>RESULTS</b>In Group B, the mean (x ± s) number of sneeze [(15.0 ± 1.3) times], scratching nose [(16.5 ± 2.3) times] and respiratory frequency [(76.3 ± 4.1) times/min] were significantly improved than those in group A [(23.5 ± 2.6) times, (26.1 ± 4.1) times and (66.5 ± 5.8) times/min, respectively), P value were 0.000, 0.000 and 0.001, respectively]. The numbers of SP-positive cells [(11.6 ± 3.6)/HP] and SP-R mRNA expression (0.64 ± 0.04) in group B were reduced significantly compared to group A [(27.1 ± 9.7)/HP, (0.83 ± 0.03), P value were 0.000, 0.000, respectively]. Sneeze [(10.0 ± 2.3) times], scratching nose [(11.8 ± 1.7) times] and respiration [(90.0 ± 5.0) times/min] in Group D were improved significantly than those in group B (P value were 0.000, 0.002 and 0.000, respectively). SP-positive cells [(2.0 ± 1.7)/HP] and SP-R mRNA expression (0.52 ± 0.06) in Group D compared with group B were also significantly reduced (P value were 0.012 and 0.000, respectively). Pathological changes in guinea pig nasal mucosa in group B, group D were alleviated than those in group A. The combination of IMETIT and Loratadine had a synergistic effect on these effects (F value were 11.59, 8.28, 5.61, 5.48, 6.50, respectively, P value were 0.002, 0.008, 0.025, 0.027, 0.017).</p><p><b>CONCLUSIONS</b>IMETIT and the combination of IMETIT with Loratadine can effectively relieve the symptoms of AR in guinea pigs, its mechanism may be relevant to reduce SP secretion and the expression of SP-R mRNA, and the two has a synergistic effect. It may be useful as a novel therapeutic approach in nasal allergy.</p>