Abstract:Objective: To investigate the effect of glucagon-like peptide 1 (GLP-1) analog liraglutide on the expression of PARP and NF-κB in diabetic peripheral neuropathy (DPN) rats by establishing a rat model of DPN. Methods: A total of 84 SD rats were randomly selected as control group, and the other rats were induced by streptozotocin to establish DPN model. After successful modeling, 72 rats were randomly divided into model group, insulin group, mecobalamin group, and liraglutide low, medium and high dose groups. Normal group and model group were subcutaneously injected with equal volume of normal saline. Insulin group was treated with insulin, mecobalamin group was treated with mecobalamin, and drug groups were treated with different doses of liraglutide for 8 weeks. The body weight and blood glucose of rats in each group were recorded, nerve reaction speed was measured, inflammatory factors were detected by ELISA, apoptosis was detected by flow cytometry, and PARP-1 and NF-κB protein expression were detected by Western blot. RSC96 cells were selected to establish cell damage model in high glucose environment. PARP target gene was predicted by gene chip and tested by transfection of PARP-1. Results: Compared with the model group, liraglutide significantly increased the body weight, significantly decreased blood glucose, and increased the speed of nerve reaction (P<0.05); rat and cell experiments showed that the content of inflammatory factors and the expression of PARP and NF-κB protein were significantly decreased after liraglutide treatment, and the reduction was more obvious in the high-dose group (P<0.05); the apoptosis rate of nerve cells in rats was significantly decreased than that in the model group (P<0.05). Liraglutide inhibited the transcriptional activity of NF-κB. The levels of inflammatory factors, PARP-1 and NF-κB protein in PARP-1 transfection group were significantly higher than those in middle dose group (P<0.05). PARP-1/NF-κB is an important target of GLP-1 in anti-inflammatory effect of diabetic neuropathy rats. Conclusion: Liraglutide can reduce the expression levels of PARP-1 and NF-κB in sciatic nerve of rats with DPN, thereby reducing the sciatic nerve injury of rats and preventing the damage of DPN.
