Effect And Mechanism Of Acupuncture Intervention On Amyotrophic Lateral Sclerosis From The Theory Of "Treating Flaccidity By Yangming"

Backgroud:Amyotrophic Lateral Sclerosis(ALS)is a fatal clinical disease caused by motor neuron injury,and is divided into familial and scattered.The pathogenesis of the disease is complex and there is no cure for ALS.Therefore,ALS is listed by the World Health Organization as one of the five major incurable diseases.Riluzole is a drug approved by the FDA for the treatment of ALS.But this drug is expensive and has large side effects.Acupuncture as a green and healthy treatment has been attracted increasing attention.It has been widely used in the treatment of neuronal injury disease and achieved good effect."The Nei Jing"has recorded the theory of"Treating flaccidity by Yangming".However,there is no research on combining this theory with acupuncture intervention in ALS.This experiment intends to explore whether acupuncture intervention in ALS with the theory of"Treating flaccidity by Yangming"is effective and its mechanism.Method:SOD1~G93A93A transgenic mice were selected as animal models.The gene phenotype was identified by PCR.They were divided into normal control group,model group and acupuncture intervention group.The normal control group and the model group were routinely raised without intervention.In the acupuncture intervention group,the Zusanli and Liangmen points were acupunctured from 60 days.The electroacupuncture was switched on 1mA,2Hz,and the intervention was performed 3 times a week for 10 minutes.The mice were sacrificed on 120 days.(1)Observe the disease progression and behavioral effects of mice in each group by recording the changes in body weight,physical signs,survival time and footprint.(2)The expression of SOD1 protein in the spinal cord of mice in each group was detected by immunohistochemistry.(3)Iba-1 protein levels in brain stem and spinal cord of mice were detected by immunohistochemistry and Western blot.(4)The expression levels of TNF-α,IL-6 and IL-1βin the spinal cord of mice in each group were detected by immunohistochemistry.Results:(1)Compared with the acupuncture intervention group and the model group,acupuncture intervention reduced weight loss,prolonged survival,and improved motor function,and the differences were statistically significant(P<0.05).At the same time,it improves the survival quality of mice and delays the development of disease.(2)The acupuncture group and the model group both had higher SOD1 levels in the spinal cord than the normal group.Compared with the model group,the acupuncture intervention group reduced the SOD1 level in the spinal cord with statistical significance(P<0.05).The deposition of SOD1 in the spinal cord had been decreased.(3)The acupuncture group and the model group both had higher Iba-1 levels in the brain and spinal cord than the normal group.The levels of Iba-1 in the brain and spinal cord of the acupuncture intervention group were lower than those in the model group,which was statistically significant(P<0.05).The results of immunohistochemistry were consistent with the results of Western blot.(4)Compared with the normal group,the levels of TNF-α,IL-6,and IL-1βin the spinal cord increased in the acupuncture group and the model group.Compared with the model group,the acupuncture intervention group reduced the TNF-α,IL-6 levels in the spinal cord.These were statistically significant(P<0.05).However,the level of IL-1βin the acupuncture intervention group decreased compared with the model group,but the difference was not statistically significant(P>0.05).The results of immunohistochemistry were consistent with the results of Western blot.Conclusion:The results show that acupuncture intervention in SOD1~G93A93A transgenic mice can effectively delay the progression of ALS and prolong the survival time of mice.The abnormal deposition of SOD1 causes lipid peroxidation and cross-linking of proteins to damage neurons.And more microglial cells are activated,which activates to produce a series of inflammatory factors.Therefore,acupuncture intervention is effective and may be related to the inhibition of microglial activation.By inhibiting the activation and proliferation of microglia,reducing its release and secretion of inflammatory factors,and the inflammatory response,and then protect neurons and delay the progression of ALS.This study can provide new ideas for clinical treatment of ALS and provide theoretical basis for acupuncture treatment of ALS.