| Objective: Tui Na therapy is widely used clinically and it has the effect of improving circulation and metabolism.In this study,we investigated the effects of "Tongluo Tiaoshen" massage on cognitive impairment and the possible mechanisms of its effects from the perspective of mitochondrial biogenesis and energy metabolism by using massage treatment on a rat model of middle cerebral artery occlusion and patients with mild cognitive impairment after stroke.Methods:1.Experimental study:(1)Effect of massage intervention on the learning and memory ability of model rats:160 male SD rats were randomly divided into 40 as sham-operated group,and the rest were modeled by MCAO,and the rats were screened into model rats by Zea-longa score after the completion of modeling,and randomly divided into model group and treatment group.The rats in the treatment group were given head,abdominal and limb pushing treatment,and the rats in the model group were put back into the cage after scratching and touching only.The rats were subjected to Zea-longa neurological function score and Morris water maze to assess the learning memory function of the rats.(2)Effect of massage intervention on neural injury and hippocampal subcellular structure damage in model rats: TTC staining was used to determine the volume of cerebral infarction in rats.Nissl staining was used to assess the severity of neuronal damage,and transmission electron microscopy was used to detect neuronal subcellular structure damage and recovery.(3)Effects of massage intervention on brain mitochondrial biogenesis and energy metabolism in model rats: Brain tissue homogenates were taken from rats,and protein and gene expression of mitochondrial biogenesis-related proteins PGC-1α,NRF-1 and TFAM were detected by protein immunoblot(Western Blot,WB)and RT-PCR in the brain.The expression of mitochondrial oxidative phosphorylation complex proteins was detected,and the changes of mitochondrial membrane potential and ATP were observed by laser confocal and flow cytometry,and ATP was detected by fluorescein to assess the mitochondrial biogenesis function and maintenance of membrane potential,ATP content in rat brain hippocampus,and the expression of brain-derived neurotrophic factor(BDNF)in brain hippocampus was assessed by WB.(4)Exploration of the potential mechanisms of action of massage intervention: The muscle tissue homogenates of the left upper limb of rats were taken to detect the expression of PGC-1α and FNDC5 protein,and to detect the irisin content in rat plasma in each group of rats to explore the potential mechanism of therapeutic action of massage to improve the learning and memory ability of rats.2.Clinical study: 67 patients with mild cognitive impairment after stroke were randomly divided into a massage group and a control group,the control group was treated with basic therapy combined with cognitive training intervention,and the massage group was treated with "Tongluo Tiaoshen" massage therapy based on cognitive training in the control group,45 min/time,5 times/week,for 4 weeks.Before and after treatment,patients’ cognitive function was assessed using the Montreal Cognitive Assessment(Mo CA),the Mini-mental State Examination(MMSE)and the modified Barthel index(MBI).Data were processed and analyzed using SPSS26.0 statistical analysis software.Results.1.Experimental studies.(1)Zea-longa scores were performed on day 7 and day 28,respectively,and the rats in the MAS group showed more significant improvement in neurological deficits than those in the MCAO group;the mean latency of rats in the MAS group in the localization cruise test was significantly shorter compared with the corresponding value in the MCAO group(P <0.05);in the spatial exploration test,rats in the MAS group traversed the target quadrant more often than those in the MCAO group(P < 0.01).(2)TTC staining: there were no infarct foci in the Sham group,and the infarct volume was significantly reduced in the MAS group compared with the MCAO group,and the difference was statistically significant;Nissler staining showed that hippocampal neurons in the Sham group were neatly arranged and compact,and neuronal death was rarely found,and damage to neurons and hippocampal body was obviously observed in the MCAO group,accompanied by the destruction of hippocampal structure,and the damage to hippocampal body was significantly improved after the push-up treatment.(2)TTC staining: there were no infarct foci in the Sham group,and the infarct volume was significantly reduced in the MAS group compared with the MCAO group,and the difference was statistically significant;Nissler staining showed that hippocampal neurons in the Sham group were neatly arranged and compact,and neuronal death was rarely found,and damage to neurons and hippocampal body was obviously observed in the MCAO group,accompanied by the destruction of hippocampal structure,and the damage to the hippocampal body after the pushing treatment was significantly improved.(3)The m RNA and protein expression levels of mitochondrial biogenesis-related factors PGC-1α,TFAM and NRF-1 were increased in the MAS group compared with the corresponding levels in the MCAO group rats;compared with the MCAO group rats,the hippocampal mitochondrial OXPHOS complex proteins CI-NDUF88,CIII-UQCRC2 and CV-ATP5 A were increased in the MAS group rats levels were increased,MMP was decreased and inhibited(P < 0.01),and the ATP content was significantly higher than the corresponding ATP concentration in the MCAO group(P < 0.05).(4)The protein expression levels of muscle PGC-1α and FNDC5 in the rats of MAS group were significantly higher than those of MCAO,the serum irisin levels were increased,and the expression of BDNF protein in the brain was elevated,with statistically significant differences compared with the MCAO group.(P < 0.05).2.Clinical study: The MMSE and Mo CA scale was used to assess the changes of cognitive level of the patients.The difference between the two groups was statistically significant(P < 0.05),especially in visuospatial and executive functions,attention and calculation power;the modified Bartholomew index scale showed that the daily living ability of patients in both groups improved,and the difference between the Tui Na group and the control group was statistically significant(P < 0.05).Conclusion:(1)massage induces mitochondrial biogenesis in the hippocampal region via PGC-1α-FNDC5/irisin-BDNF,rescuing energy deficit and thus improving learning memory dysfunction due to neurological injury after stroke.(2)The combination of “Tongluo Tiaoshen” Massage and cognitive rehabilitation training for the treatment of mild cognitive impairment after stroke can significantly improve the cognitive function and daily living activities of patients,indicating the clinical effectiveness of "Tongluo Tiao Shen" massage Massage in the treatment of cognitive impairment after stroke. |
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