Study On Mechanism Of Huangqi Guizhi Wuwu Decoction In The Treatment Of Painful Diabetic Peripheral Neuropathy Which Mediated By P2XR

BackgroundPainful diabetic peripheral neuropathy is one of a common chronic complication of diabetes,and its prevalence has gradually increased in recent years.As a commonly used traditional Chinese medicine for the treatment of painful diabetic peripheral neuropathy,Huangqi guizhi wuwu decoction has obvious effects,which can effectively alleviate pain and improve the quality of life of patients,but its mechanism of action is still unclear.Previous studies have found that Huangqi guizhi wuwu decoction can regulate the number and function of pain-related ion channels on the dorsal root ganglia?DRG?of the spinal cord to treat peripheral neuropathic pain.P2 XR belongs to the ligand-gated non-selective cation channel receptor and can be divided into seven subtypes of P2X1-7.P2X3 R and P2X7 R are distributed on DRG neurons and are closely related to pain signaling.Therefore,whether Huangqi guizhi wuwu decoction can achieve the therapeutic effect by regulating the expression of P2X3 R and P2X7 R becomes a problem which needs to be studied.ObjectiveThe purpose of this experiment was to investigate the effect of Huangqi guizhi wuwu decoction on the treatment of painful diabetic peripheral neuropathy rats and the expression of P2X3 R and P2X7 R on the DRG neurons,and to clarify its mechanism.MethodsA model of painful diabetic peripheral neuropathy was induced by intraperitoneal injection of STZ.The paw withdraw threshold and paw withdraw latency were detected using a 38450 electronic tactile tester and a thermal stinging instrument.Huangqi guizhi wuwu decoction with different concentration gradient was given for intervention,and paw withdraw threshold,paw withdraw latency,blood glucose and body weight of rats were measured at regular intervals every week,so as to comprehensively evaluate the intervention effect of Huangqi guizhi wuwu decoction.HE staining was used to observe the morphological change of DRG neurons in rats,and the expression levels of P2X3 R and P2X7 R on DRG were evaluated by immunohistochemistry.ResultsThe blood glucose of the rats with painful diabetic peripheral neuropathy was significantly higher than that of the control group?P<0.01?.The paw withdraw threshold and paw withdraw latency were significantly lower than the control group?P<0.01?.And the effect of blood glucose fluctuation on paw withdraw threshold and paw withdraw latency is linearly related.During the drug intervention,the changes in mechanical pain threshold were statistically significant?P<0.05?in the high-dose group compared with the model group after 3,5,6,7,and 8 weeks of intervention.After 5 weeks of intervention,there was a significant difference between the middle dose group and the model group?P<0.01?.There was no statistical difference between the lowdose group and model group during the intervention period?P>0.05?.In the change of paw withdraw latency,after 5,6,7 and 8 weeks of intervention,there was a statistically significant difference between the high dose group and the model group?P<0.01?.The medium and low doses were not statistically different from the model group during the intervention period?P>0.05?.In terms of P2X3 R and P2X7 R expression,high-dose Huangqi guizhi wuwu decoction could decrease the expression of P2X7 R,which was statistically different from the control group?P<0.05?.However,high,medium and low doses of Huangqi guizhi wuwu decoction had little effect on the expression of P2X3 R,and there was no statistical difference compared with the control group?P>0.05?.Conclusions?1?Rat blood glucose fluctuations may affect the paw withdraw threshold and paw withdraw latency.?2?High-dose Huangqi guizhi wuwu decoction can delay the weight loss of rats with painful diabetic peripheral neuropathy.?3?High-dose Huangqi guizhi wuwu decoction has a certain hypoglycemic effect on rats with painful diabetic peripheral neuropathy.?4?With the prolongation of intervention time,high and medium doses of Huangqi guizhi wuwu decoction can improve the paw withdraw threshold of rats and have a good analgesic effect.However,compared with the medium dose,the high dose effect is more significant and more stable and durable.?5?With the prolongation of intervention time,high-dose Huangqi guizhi wuwu decoction can improve the paw withdraw latency of rats with painful diabetic peripheral neuropathy,and has a good analgesic effect.?6?Huangqi guizhi wuwu decoction has no effect on the expression of P2X₃R.?7?High dose of Huangqi guizhi wuwu decoction can reduce the expression of P2X₇R.