| This article discusses mechanism, prevention, and treatment of noise induced hearing loss(NIHL) in hypobaric environment. In present study, guinea pigs were exposed to noise and simulated high-altitude condition to explore the impairment of auditory function and the prevention and treatment effects of salvia miltiorrhiza(SM) or tetramethypyrazine(TMP), which are expected to be of clinical value in the near future.1. The determination of SM or TMP in blood, cerebrospinalfluid and perilymph fluid of guinea pig after intramuscularThe high performance liquid chromatography (HPLC) was used to investigate the density of SM or TMP in guinea pig blood, cerebrospinal fluid and perilymph fluid after intramuscular by internal and external standard method.SM could be absorbed into blood by 10 minutes(min) after intramuscularly administration in guinea pig, and it's concentration developed to the maximum of 585.84mg/L by 80 min after injection.However, concentration of the drug in blood couldn't be detected 6 hours(6h) later. No SM could be found in cerebrospinal fluid or perilymph fluid all along. The results suggested that SM couldn't penetrate through blood-brain or blood-labyrinth barrier. SM took it's effect by way of blood rather than cerebrospinal fluid or perilymph fluid.TMP could be absorbed and transported into blood by 5min, cerebrospinal fluid by 10min, and perilymph fluid by 5min just after intramuscular injection. And it's concentration developed to the maximum by 20min, 20min, and 50min respectively. Whereas by the intramuscular injection route, and, the drug could not be detected at 2h in blood, 70min in cerebrospinal fluid, and 2h in perilymph fluid. The results indicated that TMP was rapidly absorbed and eliminated after intramuscularly administration in guinea pig. And it could penetrate through blood-brain barrier and blood-labyrinth barrier. Three ways were available, which made it possible for TMP to give its efficacy.2. Effects of SM on NIHL in hypobaric environmentNormal guinea pigs were randomized into two study groups: 1-day-exposed group and 7-day-exposed group, each group was randomized into 3 subgroups: control group, SM-injected group, SM-prophylactico-injected group (three days before exposed). All animals were exposed to 110dB white noise in hypobaric chamber modeling low pressure environment of 5500m. Acoustic brainstem response (ABR), the surface preparation, immunohistochemical staining techniques of iNOS, and transmission electron were utilized to evaluate the hearing thresholds and cochlear morphological changes. To explore the mechanism associated with SM protection, hemorheology index together with serum levels of MDA and SOD were measured.ResultsEach group had respective ABR threshold shifts, especially in4kHz. The threshold shifts developed along with the exposure time. SM has certain protective effect on NIHL in modeling hypobaric environment.The surface preparation showed more serious damages of cochlear outer hair cells(OHCs) than that of inner hair cells(IHCs), which occurred more severely in control group than in the two SM-utilized groups, and in 7-day-exposed group than in 1-day-exposed group. Immunohistochemical studies demonstrated that histological stains of iNOS appeared as golden-brown granules in stria vascularis, hair cells, spiral ganglion, especially in stria vascularis after exposure. There was no apparent immunoreactivity in the cochlea of normal guinea pigs. A increasing strong iNOS stain could be observed along with the exposure time. While the stain decreased gradually after exposure in each group. The difference among each groups is significant (p>0.05) except 1-day-exposed group with SM-injected group(p<0.05). Transmission electron microscope showed that vacuolated cytoplasm of OHCs, swelling of mitochondria, and injury of neurites and nerve fibers in control group. Such morphological changes could also be observed in the two SM-utilized groups, but they were lighter than those of control group. Moreover, the lesions were alleviated along ex... |
PDF Full Text Request