Effects And Mechanisms Of Ginkgo Leaf Extract And Dipyridamole Injection On The Plasticity Of Auditory Cortex Of Guinea Pig Following Chronic Kanamycin-induced Deafness

Objective: To investigate the effects and mechanisms of Ginkgo leaf extract and dipyridamole injection（GLEDI）on the plasticity of auditory cortex（AC）of guinea pig following chronic kanamycin-induced deafness.Methods: 1.88 adult guinea pigs were randomly divided into 11 groups,including control group（CG,n=8）,kanamycin treatment group（KTG）,and kanamycin sulfate and Ginkgo leaf extract and dipyridamole injection treatment group（KGTG）.The guinea pigs were treated with normal saline at 2ml/kg in CG,injected with kanamycin at 500 mg/kg and normal saline at 0.4 ml/kg in KTG,and kanamycin at 500 mg/kg by subcutaneous injection and GLEDI by intramuscular injection at 0.4ml/kg in KGTG every day for 7 days.There were 5 groups respectively in KTG and KGTG at 1,7,14,28 and 70 days after injection.2.5 guinea pigs of each group were injected with ¹⁸F-FDG imaging agent and scanned by PET/CT to explore the changes of glucose metabolism by observing the uptake of the imaging agent in AC.The ratios of AC and cerebellum maximum SUV values were measured.3.Expression changes of NR1,GABRA1 and IGF-1 mRNA in AC were detected by Reverse Transcription-PCR.4.The results were analyzed by ANOVA,and T-test was selected to analyze the differences between two groups.Results: 1.Changes of glucose metabolism in AC.The max ratios of SUV between AC and cerebellar were 0.76±0.02 in CG,0.76±0.02、0.74±0.06、0.72±0.02、0.73±0.05 and 0.75±0.07 in KTG,and 0.95±0.13、0.82±0.07、0.85±0.05、0.77±0.05 and 0.86±0.04 in KGTG respectively at 1,7,14,28 and 70 days after injection.GM increased in AC of KGTG in comparison with KTG at 1,14 and 70 days（P<0.05）.2.The expressions of NR1 mRNA were 0.86±0.06 in CG,0.97±0.06,1.39±0.24,1.03±0.15,0.99±0.18 and 0.93±0.14 in KTG,and 0.83±0.03,0.94±0.11,1.12±0.13,0.88±0.19 and 0.92±0.06 in KGTG respectively at 1,7,14,28 and 70 days after injection.There was an increase of NR1 mRNA,and a decline in KGTG at 7 days respectively in comparison with the CG and KTG（P<0.001）.3.The expressions of GABRA1 mRNA were 0.96±0.06 in CG,0.92±0.08,0.89±0.04,0.75±0.04,0.73±0.19 and 0.94±0.05 in KTG,and 1.32±0.01,1.19±0.09,1.06±0.05,0.81±0.06,0.8±0.03 in KGTG respectively at 1,7,14,28 and 70 days after treatment.There was an increase of GABRA1 mRNA in KTG at 14 and 28 days（P<0.001）,and a decline in KGTG at 1 day（P<0.05）respectively in comparison with the CG and KTG.4.The expression changes of IGF-1 mRNA were 0.86±0.04 in CG,0.98±0.06,1.01±0.04,0.98±0.06,0.83±0.08 and 0.81±0.03 in KTG,and 1.06±0.05,1.02±0.07,1.04±0.09,0.95±0.08 and 1.26±0.09 in KGTG respectively at 1,7,14,28 and 70 days after treatment.There was an increase of IGF-1 mRNA in KTG at 1,7 and 14 days in comparison with CG（P<0.05）,a further increase in KGTG at 70 days in comparison with the KTG（P<0.001）.Conclusions: 1.Expressions of excitatory and inhibitory neurotransmitters receptors can remodel in auditory cortex of guinea pig following chronic kanamycin-induced deafness.Changes of glucose metabolism may partly respect hearing loss.2.Ginkgo leaf extract and dipyridamole injection can promote the glucose metabolism to reconstruct the structure and function of the auditory cortex of guinea pig following chronic kanamycin-induced deafness.3.Ginkgo leaf extract and dipyridamole injection can adjust dynamic balance of NR1 and GABRA1 in order to improve the progress of reconstruction of auditory cortex after chronic deafness induced by kanamycin.4.IGF-1 may be involved in remodeling of auditory cortex of guinea pigs,and ginkgo leaf extract and dipyridamole injection may take part in the progress by increasing IGF-1 expression after chronic deafness induced by kanamycin.