Effect Of Swimming Exercise On H19 And Its Target Gene In Hippocampus Of Neuropathic Pain Mice

Background and Purpose:Neuropathic pain is one of the common clinical symptoms and is defined as "pain caused by somatosensory nervous system lesions or diseases".In recent years,swimming exercise training plays an important role in the study of neuropathic pain.Lnc RNA H19 is one of the earliest discovered lnc RNAs and is an oncogene of many cancers.Studies have shown that lnc RNA H19 regulates proliferation and degeneration of cells by targeting mir-22 through the Wnt signaling pathway,and participates in inflammatory responses.As a key component of the limbic system,the hippocampus is also believed to play an important role in pain transduction pathway and participate in the processing of various pain information,in addition to learning and memory.However,it has not been fully clarified which part of exercise training can improve sciatica.Based on the above,the objectives of this study were as follows: 1.In a neuropathic pain model induced by Sciatic Nerve Injury(SNI),the correlation between the expression of lnc RNA H19 and its target genes and pain behavior was analyzed.2.To preliminarily determine the effects of swimming exercise on key target genes of lnc RNA H19 and Wnt signaling pathway and pain behavior in hippocampus of neuropathic pain mice.Methods:Sixty C57BL/6 male mice were selected for this study.After 7 days of adaptive feeding,SNI modeling was conducted.The mice were randomly divided into Naive group,Sham group,Sham+swim group,SNI group and SNI+swim group.SNI+swim group and Sham+swim group received 6 weeks of swimming training intervention,and the other groups are routinely fed.Weight was weighed before modeling and 3,7,14,21,28,35 and 42 days after operation to ensure the health of the mice.Pain behavior tests,namely Mechanical Withdrawal Threshold(MWT)and 40% pain intensity score,were conducted to observe the changes of hyperpathia and allodynia in mice.After 6 weeks,the whole brain of mice in each group was dehydrated and fixed,and frozen sections were completed.Hematoxylin-eosin(HE)staining and Nissl staining were performed to observe the morphology and neuron structure of hippocampal tissue.The brain hippocampus of the remaining groups of mice was used for Quantitative real-time polymerase chain reaction(q RT-PCR)and Western Blotting(WB)detected the m RNA and protein expression levels of lnc RNA H19,mir-22,Wnt/β-catenin in the hippocampus.Enzyme Linked immunosorbent assay(ELISA)was used to detect inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6),antiinflammatory marker interleukin-10(IL-10)in hippocampus.Results:After SNI modeling,all performances were normal,and the body weight of mice in each group showed a trend of gradual increase,but there was no statistically significant difference in body weight at 7 different test time points(P > 0.05).On the 21 st,28th,35 th and 42 nd days after SNI modeling,MWT and 40% pain intensity score in the exercise training group were significantly higher than those in the SNI group(P < 0.01).HE staining and Nissl staining showed that neurons in the hippocampus of the SNI group were damaged and the morphology of nerve fibers was incomplete.Compared with the SNI group,the morphology of nerve fibers in the SNI+swim group was also improved and the neurons were relatively intact.q RT-PCR and WB results showed that the expression level of lnc RNA H19 in SNI group was increased(P < 0.01),the expression level of mir-22 was significantly decreased(P < 0.01),Wnt3 a and β-catenin were significantly increased(P < 0.05).ELISA showed that the levels of inflammatory factors were significantly increased and anti-inflammatory factors were decreased(P <0.01).After 6 weeks of swimming training,the expression level of mir-22 was significantly increased(P <0.01),the expression level of H19,Wnt3 a and β-catenin was significantly decreased(P <0.05),the level of inflammatory factors was significantly decreased and the level of anti-inflammatory factors was significantly increased(P <0.01).Conclusions:Swimming exercise training for 6 weeks can improve mechanical stimulation hyperalgesia and allodynia in SNI model mice;Swimming training can reverse the expression of lnc RNA H19,mir-22,Wnt3 a and β-catenin in the hippocampus of SNI model mice,and improve the inflammatory response in the hippocampus.