Peripheral Protection Mechanism Of Electroacupuncture And CO₂ Laser Moxibustion On Oxaliplatin-induced Peripheral Neurotoxicity In Rats

Objective:To discover the detoxify efficacy of EA and CO2 laser moxibustion aimed at rat peripheral neurotoxicity precipitated by oxaliplatin and their peripheral protective mechanism,and provide more effective treatment plan and experimental basis for clinical acupuncture to alleviate the side effects of chemotherapy drugs.Methods:Randomly distributed 40 male Sprague-Dawley rats to 4 groups:control group,model group,electroacupuncture group and CO₂ laser moxibustion group,and 10rats in each group.The model was made by intraperitoneal injection of 2 mg/kg of oxaliplatin solution from the first day of the experiment,once every other day for 4times.The control group receive an equal volume of 5%glucose solution by intraperitoneal injection under above protocol.After modeling 4 times?8d?,electroacupuncture and CO₂ laser moxibustion were performed on both sides of Zusanli.The electroacupuncture mode was set to 1 m A,2 Hz,30 min/time,CO₂ laser moxibustion power was 80 m V,15 min/time,both two group were treated once every other day,all about 7 times.Rats were subjected to mechanical pain sensitization test,cold stimulation sensitivity test,skin blood perfusion test before the first treatment and1 hour after each treatment.After the 7th treatment,the abdominal aorta was taken.The serum levels of ET,VEGF and NGF were observed.The morphological changes of sciatic nerve and dorsal root ganglion were observed under electron microscope.The NGF,Ca N,HO-1 and L4?L5 dorsal root ganglia NGF,Ca N and TRPA1 were determined by Western blot protein expression.Results:?1?Mechanical paw withdrawal threshold:There was significant difference existed between the model group,electroacupuncture group and CO₂ laser moxibustion group compared with the control group?P<0.01?.The difference between the electroacupuncture group and the model group was statistically significant.The significance?P<0.05?;the difference between CO₂ laser moxibustion group and model group was not statistically significant?P>0.05?;the difference between CO₂ laser moxibustion group and electroacupuncture group was statistically significant?P<0.05?.?2?Cold stimulation sensitivity:The difference between the model group and the electroacupuncture group was statistically significant?P<0.01,P<0.05?.There was no statistical difference between the CO₂ laser moxibustion group and the control group.The significance of learning?P>0.05?;electroacupuncture group,CO₂ laser moxibustion group and model group were significantly different?P<0.01?;there was no significant difference was found between CO₂ laser moxibustion group and electroacupuncture group?P>0.05?.?3?Skin blood perfusion:There were existing significant difference was found between the model group,the electroacupuncture group and the CO₂ laser moxibustion group compared with the control group?P<0.01?.The electroacupuncture group and the CO₂ laser moxibustion group had compared with the model group,there was significant difference existed between them?P<0.01?;there was no significant difference was analyzed between CO₂ laser moxibustion group and electroacupuncture group?P>0.05?.?4?Morphological changes under the electron microscope of sciatic nerve and dorsal root ganglion:compared with the control group,the sciatic nerve of the model group showed more severe myelin degeneration,neurons,nuclei and benevolents in dorsal root ganglion neurons.Different degrees of pyknosis and mitochondrial swelling.?5?Serum ET:There was no significant difference was summarized between the model group,the electroacupuncture group and the CO₂ laser moxibustion group compared with the control group?P>0.05?.There was existing significant difference was found between the electroacupuncture group and the model group?P<0.05?;There was no significant difference was found between CO₂ laser moxibustion group and model group and electroacupuncture group?P>0.05?.?6?Serum VEGF:There was no significant difference was analyzed between the electroacupuncture group and the model group compared with the control group?P>0.05?.The difference between the CO₂ laser moxibustion group and the control group was statistically significant?P<0.05?.The difference between the electroacupuncture group and the CO₂ laser moxibustion group was significant difference?P<0.05?.There was no significant difference was found between the CO₂ laser moxibustion group and the electroacupuncture group?P>0.05?.?7?Serum NGF:There was no significant difference between the groups?P>0.05?.?8?NGF protein expression in sciatic nerve:There was no significant difference was found between the electroacupuncture group and the model group compared with the control group?P>0.05?.The difference between the CO₂ laser moxibustion group and the control group was significant difference?P<0.05?;There was no significant difference was summarized between the CO₂ laser moxibustion group and the electroacupuncture group and the model group?P>0.05?.The difference between the electroacupuncture group and the CO₂ laser moxibustion group was statistically significant?P<0.05?.?9?Ca N protein expression in sciatic nerve:There was no significant difference was found between the CO₂ laser moxibustion group,model group,and the electroacupuncture group compared with the control group?P>0.05?.The electroacupuncture group and CO₂ laser moxibustion group were compared with the model group.The difference was significant difference?P<0.05?.There was no significant difference was summarized between the electroacupuncture group and the CO₂ laser moxibustion group?P>0.05?.?10?HO-1protein expression in sciatic nerve:There was no significant difference was analyzed between the model group and the electroacupuncture group compared with the control group?P>0.05?.The difference between the CO₂ laser moxibustion group and the control group was statistically significant.?P<0.05?;the difference between the electroacupuncture group and the model group was not statistically significant?P>0.05?;the difference between the CO₂ laser moxibustion group and the model group was statistically significant?P<0.05?;the electroacupuncture group Compared with the CO₂ laser moxibustion group,the difference was statistically significant difference?P<0.05?.?11?NGF protein expression in dorsal root ganglion:There was no significant difference between model group,electroacupuncture group and CO₂ laser moxibustion group and control group?P>0.05?;electroacupuncture group,CO₂ laser moxibustion group difference with the model was statistically significant?P<0.05,P<0.01?.There was no significant difference was found between the electroacupuncture group and the CO₂ laser moxibustion group?P>0.05?.?12?The expression of Ca N protein in dorsal root ganglion:There was no significant difference in the rats of each group?P>0.05?.?13?TRPA1 protein expression in dorsal root ganglia:The difference between the model group and the electroacupuncture group was statistically significant?P<0.05?.There was no difference in the CO₂ laser moxibustion group compared with the control group.The significance of learning?P>0.05?;electroacupuncture group,CO₂ laser moxibustion group and model group,there was no significant difference existed between them?P>0.05?;electroacupuncture group compared with CO₂ laser moxibustion group,there was no significant difference was summarized between them?P>0.05?.Conclusion:?1?Electroacupuncture and CO₂ laser moxibustion can alleviate the neuropathic pain induced by oxaliplatin,increase the blood perfusion of the skin,and have a certain protective effect on the peripheral neurotoxicity induced by oxaliplatin.?2?Electroacupuncture and CO₂ laser moxibustion may reduce oxaliplatin-induced peripheral neuropathy by protecting NGF,Ca N,HO-1 proteins in nerves and ganglia and increasing the levels of ET and VEGF in peripheral blood.