| Since streptomycin was discovered in the 1940's,Aminoglycoside antibiotics (AmAn) has been applied for more than a half century. Due to its high efficacy with low cost, it is still one of the most widespread antibiotic. Nevertheless, because of its' ototoxicity and nephrotoxicity, it has been limited in most countries. Some scholars believe that the second messenger in the cochlea links to the AmAn ototoxicity, but some argue that glucose transport and its dysmetabolism leads to ototoxicity, or that the adverse reaction of free radical in the cochlea brings lipid peroxidation and finally results in ototoxicity. With the investigation deep-going, people found that the sensitivity of AmAn ototoxicity has tight connection with mitochondrial gene. It is obvious that ototoxicity pathogenesis resulted from AmAn is still in ceaseless dispute, and how to prevent and cure AmAn ototoxicity is also far from unanimousness. Whereas, this experiment mainly investigated from the aspects hereinafter:1 .The extent of ototoxicity to guinea pig by gentamicin and netilmicin, and the effect of the concentration of ferric ion and the superoxide dismutase (SOD) activeness to ototoxicity.2.The relation between cell apoptosis and AmAn ototoxicity of guinea pig.3.The similarities and difference between antioxidant prevention and antioxidant therapy of AmAn ototoxicity, and the antagonistic effect of N-methyl-D-aspartate (NMDA) receptor antagonist to AmAn ototoxicity.4.Whether A1555G mitochondrial DNA mutation in 12SrRNA gene is the only molecule elements of genetic predisposition of AmAn ototoxicity.We divided the gentamicin group and netilmicin group into one-week group and two-week group separately, compared the toxicity of these two most common used clinical AmAn horizontally and vertically, and studied the relation between these two kinds of drugs and the apoptosis of guinea pig's hair cell. Selecting Deferoxamine mesylate , Reduced Glutathione for injection and Ginaton Injection solution in prevention and treatment of the guinea pig's netilmicin ototoxicity, and comparing the similarities and difference between their effectiveness, we demonstrated the antagonism of N-methyl-D-aspartate (NMDA) receptor antagonist to the netilmicinototoxicity. We amplified the study segment through polymerase chain reaction, and studied whether the change of the position digested by Alw26I in human mtDNA12SrRNA also exists in guinea pig utilizing the characteristic of restriction enzyme which can digest definite nucleotide sequence. At the same time, we obtained the complete sequence of the guinea pig's mitochondrial through direct sequencing, and compared the known sequence of the guinea pig in the gene bank, looking for possible change of the mitochondrial DNA sequence relating with AmAn ototoxicity. From our experiments we found some results as follows:One-week and two-week group of gentamicin results in significant decline of auricle reflex threshold, heightening of acoustic brainstem evoked respone and delay of III wave, comparing with those groups of netilmicin separately.The concentration of ferric ion in group GB,NB,GA and NA is significantly higher than it in group SB and SA, indicating that occurrence of AmAn ototoxicity closely relates with the heightening of concentration of ferric ion, but the concentration of ferric ion in group GA and NA is higher than it in group GB and NB. SOD activeness in group GA, GB, and NA, NB is strikingly lower than it in group SA and SB separately, indicating that occurrence of AmAn ototoxicity relates with the descent of SOD activeness in the body. Finding that SOD activeness in gentamicin group declines much more than it in netilmicin group, it indicates that at the same time point, the extent of ototoxicity relates with SOD activeness.Through scanning electron microscope, we find that damage to hair cell caused by gentamicin is evidently higher than it caused by netilmicin, and the most evident damage to hair cell caused by these two kinds of drugs both concentrates in basal turn hair cell, gradually expanding to the apex.Gentamicin and netilmicin both can create cells apoptosis of Corti of guinea pig, and the occurrence of apoptosis links with the extent of ototoxicity positively .Using Deferoxamine mesylate in preventing and treating netilmicin ototoxicity can increase auricle reflex, reduce acoustic brainstem evoked respone, minish time delay of III wave and lower serum ferric ion consistency. Furthermore, Deferoxamine mesylate prevention group can attenuate netilmicin ototoxicity much better than treatment group.Using Reduced Glutathione in preventing and treating netilmicin ototoxicity can also increase auricle reflex ,reduce acoustic brainstem evoked respone, minish time delay of III wave and increase SOD activeness, but it doesn't affect ferric ion consistency, and the effect of... |
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