| 1 Objective:To observe the effect of Gandouling combined with repetitive transcranial magnetic stimulation on WD with cognitive dysfunction,and to study the effect of Gandouling on cognitive function and protective mechanism of neural stem cells in mice with high copper load.It provides new ideas for the treatment of WD with cognitive impairment,and provides a research basis for the neuroprotective effect of Gandouling on high copper-induced neural stem cell injury mice and its molecular mechanism.2 Methods:2.1 Clinical researchAccording to the inclusion criteria,eighty-six cases of WD patients with cognitive dysfunction were randomly selected from February 2019 to December 2019 at the Encephalopathy Center of the First Affiliated Hospital of Anhui University of Chinese Medicine.There was no significant difference in education level,course of disease,gender,and age.The control group was treated with sodium dimercaptopropanesulfonate injection,the Gandouling group was treated with sodium dimercaptopropanesulfonate injection combined with traditional Chinese medicine compound liver bean spirit,and the rTMS group was treated with sodium dimercaptopropanesulfonate injection and traditional Chinese medicine compound liver bean Spirit and rTMS treatment.The MMSE scale and MoCA scale were used to evaluate the cognitive function of patients before and after treatment.Prospective memory tests were performed on patients before and after treatment.Serum Hcy levels were examined before and after treatment.The changes of MMSE,MoCA,TBPM,EBPM scale scores and serum Hcy levels in the three groups were compared.2.2 Experimental researchSeventy-three SD rats were randomly divided into a control group,a high coppermodel group,and a high-dose,medium-dose,and low-dose treatment group of Gandouling.The dosage is calculated according to the body surface area conversion algorithm,and is converted according to the daily dosage of a 70 kilogram adult.Gandouling is dissolved in 8ml solution every 0.3g,the dose in the low-dose group is0.48g/kg/d,the medium-dose group is 0.96g/kg/d,and the high-dose group is1.92g/kg/d.The control group and model group were administrated with an equal volume of normal saline.After seven days,the T-arm maze was used to observe changes in spatial learning and memory abilities of rats.Hippocampus tissues of fourteen-day-pregnant ICR mice were divided into control group,model group,and high-,medium-,and low-dose groups treated with Gandouling.The control group was added with 10%SD rat blank serum,and the model group used 10%SD.Rat blank serum copper load medium was cultured,and liver bean spirit low,medium and high dose groups were cultured with 10% liver bean spirit drug serum copper load medium prepared in three different doses,and ROS levels of neural stem cells were measured by flow cytometry.3 Results:3.1 Clinical research3.1.1 Comparison of MoCA and MMSE total scores in the three groupsThere was no significant difference in the changes of total MoCA and MMSE scores in the control group before and after treatment(P> 0.05).The Gandouling group and the rTMS group had a higher MoCA score compared with the pre-treatment group,and the difference was statistically significant(P <0.01).The total Dosage of Gandouling group was increased compared with the control group,and the difference was statistically significant(P <0.05).The total MoCA score of the rTMS group was significantly increased,the difference was statistically significant(P <0.01).The total MoCA score increased compared with the Gandouling group,and the difference was not statistically significant(P> 0.05).There was no significant difference in MMSE score between the groups(P> 0.05).It is suggested that Gandouling can improve the cognitivelevel of patients with WD and cognitive dysfunction,and the effect of combining rTMS is better.3.1.2 Comparison of space,execution score and memory score in MoCA scaleComparison of space and execution score in MoCA scale.The scores of Gandouling group and rTMS group were increased compared with those before treatment,and the difference was statistically significant(P <0.05).The Gandouling group showed higher scores and no significant difference compared with the control group(P> 0.05).The rTMS component value increased and the difference was statistically significant(P <0.05).The rTMS group had higher scores than the Gandouling group,and the difference was not statistically significant(P> 0.05).Comparison of memory scores on MoCA scale.The scores of Gandouling group and rTMS group were increased compared with those before treatment,and the difference was statistically significant(P <0.05).The score of Gandouling group was improved compared with the control group,and the difference was not statistically significant(P>0.05).The rTMS component value was increased,and the difference was statistically significant(P <0.05).By comparison,the scores increased,and the difference was not statistically significant(P> 0.05).It suggests that Gandouling can improve the spatial,executive and memory levels of patients with WD with cognitive dysfunction,and the effect of rTMS combined is better.3.1.3 Comparison of EBPM and TBPM scores in the three groupsComparison of three groups of EBPM scores.The scores of Gandouling group and rTMS group were increased compared with those before treatment,and the difference was statistically significant(P <0.05).The score of Gandouling group increased after treatment compared with the control group,and the difference was not statistically significant(P> 0.05).The rTMS component value was increased,and the difference was statistically significant(P <0.01).The rTMS group had a higher score compared with the Gandouling group,and the difference was statistically significant(P <0.05).Comparison of three groups of TBPM scores.The scores of Gandouling group andrTMS group were increased compared with those before treatment,and the difference was statistically significant(P <0.05).The scores of Gandouling group increased compared with the control group after treatment,and the difference was not statistically significant(P> 0.05);rTMS component values increased,and the difference was statistically significant(P <0.05);rTMS group and Gandouling group By comparison,the scores increased without significant differences(P> 0.05).It suggests that Gandouling can improve the prospective memory of patients with WD and cognitive dysfunction,and combined with rTMS is more effective.3.1.4 Comparison of serum Hcy scores in the three groupsThe Hcy level in the control group was lower than that before treatment,and the difference was statistically significant(P <0.05).The Hcy level in the Gandouling group and rTMS group was lower than before treatment,and the difference was statistically significant(P <0.01).The Gandouling group and the rTMS group showed a significant difference in Hcy level compared with the control group after treatment(P <0.05);the rTMS group had no significant difference with the Gandouling group(P> 0.05).It is suggested that Gandouling can effectively reduce the serum Hcy level in patients with WD.3.2 Experimental research3.2.1 Behavioral ResultsThere was no statistically significant difference in the time(S)before the groups entered the electrical stimulation area(P> 0.05).The low-dose group,and the middle-dose group,the time to enter the electrical stimulation zone was prolonged compared with the model group,and the difference was statistically significant(P<0.01).The model group,low-dose group,and middle-dose group had a longer time to enter the electrical stimulation zone compared with the control group,and the differences were statistically significant(P <0.01).The time of entering the electrical stimulation zone was reduced in the middle-dose group compared with the model group,and the difference was statistically significant(P <0.05).Compared with the high-dosegroup,the time to enter the electrical stimulation zone was reduced,and the difference was statistically significant(P <0.01).It is suggested that the mice with high copper load have obvious spatial learning and memory dysfunction,and the ability of spatial learning and memory improves after treatment with medium and high dose Gandouling.3.2.2 ROS test resultsThe model group,low-dose and middle-dose groups had higher ROS levels compared with the control group,and the differences were statistically significant(P<0.01).The level of ROS decreased compared with the high-dose group,and the difference was statistically significant(P <0.05).This shows that high copper load can lead to increased ROS levels,and the drug has a certain repair effect on the damage caused by the model.4 Conclusion:4.1 The traditional Chinese medicine Gandouling can improve the cognitive function of patients with WD,especially in terms of spatial execution and memory.Gandouling combined with rTMS has a better effect.4.2 Gandouling can reduce serum Hcy levels in patients with WD.4.3 Gandouling can reduce the level of ROS in neural stem cells and improve the spatial learning and memory ability of rats with high copper load. |
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