Study Of The Mechanism On Interleukin 10 Improving The Learning-memory Function In The Hypoxic Ischemic Brain Damaged Rats

Objective To investigate the effects and mechanism of interleukin-10(IL-10)on the restoration of learning-memory function in the HIBD rats.Methods The HIBD rats were injected by AVV-IL-10-shRNA in hippocampus to block IL-10 expression.The brain tissue were collected to observe AVV infection in the hippocampus of HIBD rats.The levels of TLR2 and p65 mRNA and protein expressions were detected by real-time PCR and western blotting,and the expression level of IL-10 was tested by ELISA.Morris water maze test was used to detect rats' learning-memory function,object-in-place to investigate the ability to explore new things of rats,and patch clamp technique to test the long-term potentiation(LTP)of hippocampal brain slice in the rats following AAV-IL-10-shRNA infection.After NF?B inhibitor PDTC treatment for 9h,the levels of TLR2,P65 and IL-10 expressions were detected in the hippocampus of HIBD rats.Results(1)The level of IL-10 expression was significantly increased at 14 days,and reached the peak platform at 21~28 days following HIBD.(2)The learning-memory function and ability to explore new things of therats injected by the AAV-IL-10-shRNA were significantly decreased compared with those of the AAV-control-shRNA group(P<0.05).Results of patch clamp showed that the increase of fEPSP slope in the hippocampal brain slice of the AAV-IL-10-shRNA rats were less than that of the AAV-control shRNA group(P<0.05,P<0.001).(3)The AAV-IL-10-shRNA downregulated level of IL-10 expression(P<0.001),but no affected to the levels of TLR2 and P65 expressions.PDTC,NF?B inhibitor,specifically downregulated the levels of p65 expression(P<0.01),but also decreased IL-10 secretion in the hippocampus tissue(P<0.05),but no significant difference in the TLR2 expression level.Conclusions IL-10 can improve spatial learning–memory function of HIBD rats,increase the ability of exploring new things,and enhance long term potentiation of hippocampal brain slice.Furthermore,TLR2/p65 signaling pathway regulates IL-10 expression level in the hippocampus of the HIBD rats.