Effect of HDAC2/Inpp5f on neuropathic pain and cognitive function through regulating PI3K/Akt/GSK-3β signal pathway in rats with neuropathic pain

摘要

The effect of histone deacetylase (HDAC)2/Inositol polyphosphate-5-phosphatase F (Inpp5f) on neuropathic pain and cognitive dysfunction through regulating PI3K/Akt/GSK-3β signal pathway in rats with neuropathic pain was investigated. A total of 80 SPF mature male SD rats were averagely randomized into the sham operation group, the model group, the HDAC2 intervention group (group A) and the Inpp5f intervention group (group B). The rat models of neuropathic pain were established in the model group, and groups A and B. At the 15th day after modeling, rats in group A were transfected with the interference vector of HDAC2, and rats in group B were transfected with the overexpression vector of Inpp5f. Rats in the four groups were observed before modeling, after modeling/before intervention and 3 days after intervention in terms of paw thermal withdrawal latency (PWL), paw withdrawal mechanical threshold (PWT) and changes in cognitive function (Morris water maze and passive avoidance task). Then the rats were sacrificed. RT-qPCR and western blot analysis were used to detect the levels of HDAC2 mRNA, Inpp5f mRNA, phosphorylated PI3K (p-PI3K), phosphorylated AKT (p-AKT), phosphorylated GSK-3β (p-GSK-3β) in rat brain tissue. Correlation of HDAC2 mRNA with Inpp5f mRNA expression levels was detected by Pearsons correlation analysis. Compared with the sham operation group, PWL was significantly lower while PWT was higher in the other 3 groups (P<0.05). Three days after intervention, PWL was significantly higher while PWT was significantly lower (P<0.05). Inhibiting the expression of HDAC2 or promoting the expression of Inpp5f can effectively improve cognitive function in rats (P<0.05). After intervention, compared with the sham operation group, rats in the other 3 groups had higher HDAC2 mRNA level and lower Inpp5f mRNA level (P<0.05). In conclusion, neuropathic pain can cause an increase in HDAC2 expression level and a decrease in Inpp5f expression level, and activate the PI3K/Akt/GSK-3β signal pathway. Inhibition of HDAC2 expression can inhibit the activation of PI3K/Akt/GSK-3β signal pathway through increasing Inpp5f expression, thus improving the condition and cognitive disorder of rats with neuropathic pain.