Molecular Mechanism Of Hypercholesteremia Induced Hearing Loss

The models of hypercholesteremia rats were founded and thetechniques of molecular biology were used to identify mitochondrial DNA(mtDNA) deletions associated with hypercholesteremia and noise exposure,and to investigate the molecular mechanism of the hearing loss induced byhypercholesteremia. The preliminary study was composed of two partsbelow:Part â… . Mitochondrial DNA⁴⁸³⁴ deletions associated with rathypercholesteremia.Objective To determine whether or not the rat hypercholesteremiacontributed to hearing organs mtDNA⁴⁸³⁴ deletion and involved in thedevelopment of hearing loss. Methods Founding the hypercholesteremiamodel by feeding the experimental group (38 rats) with high cholesterol dietand feeding the control group (22 rats) with common diet for 6 months. Therats were tested for auditory sensitivity using auditory brainstem response(ABR). The left cochlea (experimental group 21, control group 10) and theleft cochlear nucleus (experimental group 27, control group 13) wereharvested and the total DNA was extracted. MtDNA was amplified by nestPCR to examine the presence of mtDNA⁴⁸³⁴ deletion. Results The resultshowed: (1) There was a significant increase in the level of serumcholesterol and ABR threshold in the experimental group. (2) The highconserved mitochondrially- encoded tRNA and ND1 segments wereamplified from all samples, as well as mtDNA⁴⁸³⁴ deletions related tohyPercholesteremia. (3) The incidence of carrytng mtDNA4"' deletions inhearing organs with hrpercholesteremia rats was significant higher than thatof control grouP (P<0.05). Conclusion Extended hyPercholesteremiacould induce hearing loss and in rat, and mtDNA4834 deletion in the hearingorgans might be one of the pathogenic ways.Part II. Mitochondrial DNA4834 deletions associated with rathypercholesteremia and noise exposure.Objective To determine whether or not the rat hyPercholesteremiaand noise exposure contributed to hearing organs mtDNA'83' deletion andinvolved in the development of hearing loss. MetI1ods Founding thehyPercholesteremia model by feeding the group 3 (10 rats) with highcholesterol diet and feeding the group 4 (8 rats) with cornmon diet fOr 6months. Then the rats were exposed to noise for 40 days (l l4 dB SPL whitenoise for 4 hour/day). The rats were tested for auditory sensitivity usingauditory brainstem response (ABR). The left cochlea cochlear nucleus wereharvested and the total DNA was extracted. MtDNA was amplified by nestPCR to examine the presence of mtDNA48" deletion. Results The resultshowed: (l) There was a significant increase in the level of serumcho1esterol and ABR threshold in the grouP 3. (2) Both of the two grouPsrats' ABR threshold increase but the gaP of ABR thresholds of two grOupswas decreased after noise exposure. (3) The incidences of mtDNA'83'deletions in the hearing organs with hrpercholesteremia and noise exposure(group 3), noise exposure (group 4) and hapercholesteremia rats were closeto each other, but all were significant higher than that of control group- 5 -Absthect bo DNA forAndwM - edNforndHWha(P<0.05). Conclusion Both of noise exposure and extendedhyPercholesteremia could induce hearing loss and mtDNA'83' deletion inhearing organs in rats, but the influence of noise exposure was moreefficient than that ofhyPercholesteremia.In conclusion, both of noise exposure and extendedhyPercholesteremia could induce hearing loss and mtDNA"3' deletions inhearing organs. There was a close relationship betWeen mitochondrialDNA"a' deletions and the hearing loss induced by noise exposure andhyPercholesteremia. It was suggested that the mtDNA"" deletions was notonly associated with aging, but also associatied with hyPercholesteremiaand noise exposure.