| Purpose:Based on the source of Ancient Literature,this paper discusses the correlation between kidney-yang,du-meridian and nao-shen from the angle of yang-deficiency leading to depression,and sums up the positive reaction points of du-meridian in primary depression(kidney-yang deficiency syndrome)and their compatibility law according to the theory of acupoint sensitization,it is suggested that the method of “Wen Shen Tong Du”is feasible to treat primary depression(kidney-yang deficiency syndrome),and the possible mechanism of “Wen Shen Tong Du”acupuncture to depression model rats with kidney-yang Deficiency Syndrome is discussed from the point of RAP1 signal pathway.Materials and Methods:1 Literature part: Retrieval and comb the ancient Literature part from the Spring and Autumn and Warring States Period to Ming and Qing Dynasties,and explore the understanding and pathogenesis of depression by ancient physicians.2 Clinical part:146 clinically recruited volunteers were used as the research objects(including 73 patients with kidney-yang deficiency type depression and 73 healthy people),using infrared thermal imaging device and traditional acupoint diagnosis method to examine the volunteers' body surface temperature and tenderness in Du Channel.3 Experimental part:SD rats,30,half male and half,250±50g,were randomly divided into five group: normal group,model group,warm acupuncture group,inhibitor group,warm acupuncture and inhibitor combined intervention group,6 rats in each group.Except for the normal group,the rest of the groups were modeled with hormones combined with chronic stress stimulation;warm needling group and warm acupuncture and inhibitor combined intervention group used acupuncture and moxibustion for intervention;warm acupuncture and inhibitor combined intervention group and inhibitor group rats were fed ESI-09(dose of10mg/kg)prior to animal death,anatomy and materials.Sugar water preference experiment,forced swimming,open field test and Morris water maze to test whether the model is successful and the effect of “Wen Shen Tong Du” acupuncture method on the behavior of depression model rats with kidney yang deficiency;Elisa method detects BDNF,5-HT,DA,NE,GC content in each group;Western blot detect the RAP1 signaling pathway of c AMP,RAP1,MEK,ERK1/2,CREB protein expression.Result:Literature part: From the perspective of Yang Qi,the ancient literature on depression syndrome is sorted out,and it is learned that both viscera yang deficiency and yang deficiency constitution affect the occurrence and development of depression syndrome,however,its pathogenesis is particularly close to kidney yang deficiency.Clinical part:1 Comparison of the temperature of Du Channel acupointsCompared with the healthy group,the temperature of Yaoshu,Yaoyangguan,Mingmen,Jizhong,Zhongshu,Zhiyang,Lingtai,Shendao,Taodao,Fengfu,Naohu,Baihui,and Yintang points in the observation group were significantly lower(P<0.05 or P<0.01);the temperature of Xuanshu,Jinsuo,Shenzhu,Dazhui,Yamen,Qiangjian,Houding,Qianding,Xinhui,Shangxing,Shenting,Suliao,Shuigou,Duiduan points in the observation group was no significant difference(P>0.05).2 Positive rate of Tenderness at Du ChannelThe results show that 73 patients with kidney-yang deficiency depression,4 cases had no obvious tender points,69 cases had obvious tender points,and the incidence of tender points was 94.5%.There is a certain regularity in the distribution of tenderness points.The back and waist are mainly concentrated between Lingtai and Yaoshu,and the head is mainly concentrated at Baihui and Yintang.3 Comparison of the VAS value of Du Channel acupoint tendernessCompared with the healthy group,the VAS value of tenderness in Yaoshu,Yaoyangguan,Mingmen,Xuanshu,Jizhong,Zhongshu,Zhiyang,Lingtai,Shendao,Shenzhu,Taodao,Fengfu,Naohu,Baihui,Yintang in the observation group were significantly increased(P<0.05 or P<0.01);the VAS value of tenderness in Jinsuo,Dazhui,Yamen,Qiangjian,Houding,Qianding,Xinhui,Shangxing,Shenting,Suliao,Shuigou,Duiduan points in the observation group was no significant difference in the VAS value of tenderness in the Duiduan acupoint area(P>0.05).4 Cluster analysis of Du Channel positive reaction pointsThe results show that the Du Channel positive reaction points can be divided into two categories,one is the main Du Channel positive reaction points including Baihui,Yintang,Yaoyangguan,and Mingmen;the other is the secondary reaction points are 4 cluster groups,including 1)Naohu,Yaoshu,Fengfu 2)Jizhong,Taodao,Zhiyang 3)Lingtai,Shendao 4)Zhongshu.5 Analysis of the association rules of Du Channel positive reaction pointsThe results show that there are a total of 207 second-order to fourth-order association rules.The application software analyzes the compatibility law of Du Channel positive reaction points.In the second-order association,the compatibility of Baihui and Yintang is the most frequently used,with a support of 88.693 and a confidence of 96.1;the support of Mingmen and Yaoyangguan is 69.717,which confidence is 94.1.In the third-order association,when Baihui and Yintang are used together,the chance of Mingmen appearing is greater.In the network association diagram of the compatibility of acupoints in depression of kidney yang deficiency,the number of links between Baihui and Yintang is 191,the number of links between Baihui and Mingmen is 159,and the number of links between Baihui and Yaoyangguan is 131,and the number of links between Yintang and Mingmen is 114,the number of links between Yintang and Yaoyangguan is 113,and the number of links between Mingmen and Yaoyangguan is 112.The thickness of the link line is proportional to the degree of association;the larger the number of links,the thicker the connection line,the stronger the association;on the contrary,the smaller the number of links,the thinner the connection line,and the weaker the association.Experimental part:1 Effect of “Wen Shen Tong Du” Acupuncture Method on Behavior of Depression Model Rats with Kidney Yang Deficiency1.1 General observationCompared with the normal group,the rats in the model group and the inhibitor group show slow movement,lethargy,decreased appetite,lack of luster,lethargy,and loose stools;the general situation of appeals in warm acupuncture group and warm acupuncture and inhibitor combined intervention group after the treatment of “ Wen Shen Tong Du ”acupuncture was significantly improved.1.2 WeightBefore treatment,the weight change of each group was not statistically significant(P>0.05).After treatment,compared with the normal group,the body weight of the model group?warm acupuncture group?inhibitor group and warm acupuncture and inhibitor combined intervention group were significantly reduced(P<0.01);compared with the model group,the weight of the inhibitor group was significantly reduced(P<0.05),the body weight of the warm acupuncture group and the warm acupuncture and inhibitor combined intervention group increased to different degrees(P<0.05 or P<0.01);compared with the warm acupuncture group,the body weight of the inhibitor group and the warm acupuncture and inhibitor combined intervention group decreased significantly(P<0.01).1.3 Rectal temperatureBefore treatment,the changes of rectal temperature in each group were not statistically significant(P > 0.05).After treatment,compared with the normal group,the rectal temperature of the model group?warm acupuncture group?inhibitor group and the warm acupuncture and inhibitor combined intervention group were significantly lower(P<0.01);compared with the model group,the inhibitor group's rectal temperature was significantly lower(P < 0.05),in which the warm acupuncture group and the warm acupuncture and inhibitor combined intervention group increased(P < 0.01);compared with the warm acupuncture group,the rectal temperature of the inhibitor group was significantly lower(P<0.01),and there was no significant difference in the rectal temperature of the temperature suppression group(P>0.05).1.4 Sugar water preference experimentBefore treatment,the consumption of sugar and water in each group was not statistically significant(P>0.05).After treatment,compared with the normal group,the sugar and water consumption of the model group?warm acupuncture group?inhibitor group and the warm acupuncture and inhibitor combined intervention group were significantly reduced(P<0.01);compared with the model group,the sugar and water consumption of the inhibitor group was significantly reduced(P<0.05),in which the warm acupuncture group and the warm-suppression group increased(P<0.05 or P<0.01);compared with the warm acupuncture group,the consumption of sugar and water in the inhibitor group and the warm-suppression group decreased significantly(P<0.01).1.5 Forced swimming experimentBefore treatment,the swimming immobility time of each group was not statistically significant(P>0.05).After treatment,compared with the normal group,the swimming immobility time of the model group?inhibitor group and the warm acupuncture and inhibitor combined intervention group were all prolonged(P<0.01),in which the warm acupuncture group did not change(P>0.05);compared with the model group,the swimming immobility time of the inhibitor group was significantly prolonged(P < 0.01),in which the warm acupuncture group and the warm acupuncture and inhibitor combined intervention group was shortened to a certain extent(P<0.05 or P<0.01);compared with the warm acupuncture group,the swimming immobility time of the inhibitor group and the warm acupuncture and inhibitor combined intervention group were significantly prolonged(P<0.01).1.6 Open field testBefore treatment,the residence time of the central grid within 10 minutes of each group of experimental rats was not statistically significant(P>0.05).After treatment,compared with the normal group,the residence time of model group?warm acupuncture group?inhibitor group and the warm acupuncture and inhibitor combined intervention group were significantly reduced(P<0.01);compared with the model group,the residence time of inhibitor group was significantly reduced(P<0.01),the warm acupuncture group and warm acupuncture and inhibitor combined intervention group increased(P<0.05 or P<0.01);compared with the warm acupuncture group,the inhibitor group and the warm acupuncture and inhibitor combined intervention group were significantly shorter(P<0.05 or P<0.01).Before treatment,the open movement distance of rats in each group was not statistically significant(P>0.05).After treatment,compared with the normal group,the movement distance of the model group ? warm acupuncture group ? inhibitor group and the warm acupuncture and inhibitor combined intervention group were significantly shortened(P <0.01);compared with the model group,the inhibitor group was significantly shortened(P<0.01),the warm acupuncture group and the warm acupuncture and inhibitor combined intervention group increased(P<0.01);compared with the warm acupuncture group,the inhibitor group and the warm acupuncture and inhibitor combined intervention group were significantly shortened(P<0.01).1.7 Morris water mazeBefore treatment,the platform incubation period of each group was not statistically significant(P>0.05).After treatment,compared with the normal group,the model group?warm acupuncture group?inhibitor group and the warm acupuncture and inhibitor combined intervention group were significantly shortened(P<0.01);compared with the model group,the inhibitor group was significantly shortened(P<0.01),the platform incubation period of the warm acupuncture group and the warm acupuncture and inhibitor combined intervention group were prolonged(P<0.01);compared with the warm acupuncture group,the inhibitor group was shortened(P < 0.01),and there was no difference of warm acupuncture and inhibitor combined intervention group(P>0.05).Before treatment,there was no statistically significant change in the number of platform shuttles of each group(P>0.05).After treatment,compared with the normal group,the number of shuttles in the model group?warm acupuncture group?inhibitor group and the warm acupuncture and inhibitor combined intervention group were significantly reduced(P<0.01);compared with the model group,the inhibitor group was significantly reduced(P<0.01),the warm acupuncture group and the warm acupuncture and inhibitor combined intervention group increased(P<0.01);compared with the warm acupuncture group,the inhibitor group decreased(P < 0.01),and the number of shuttles increased in the warm acupuncture and inhibitor combined intervention group(P>0.05).Before treatment,the proportion of platform quadrant time in each group was not statistically significant(P>0.05).After treatment,compared with the normal group,the model group?warm acupuncture group?inhibitor group and warm acupuncture and inhibitor combined intervention group were significantly reduced(P<0.01);compared with the model group,the inhibitor group was significantly reduced(P<0.01),the warm acupuncture group and the warm acupuncture and inhibitor combined intervention group increased(P<0.01);compared with the warm acupuncture group,the inhibitor group decreased(P<0.01),and warm acupuncture and inhibitor combined intervention group increased(P>0.05).2 The effect of “Wen Shen Tong Du” Acupuncture Method on hippocampal nerve plasticity in the depression model rats with kidney-yang deficiencyCompared with the normal group,the contents of BDNF?5-HT? DA?NE,and GC in the model group? warm acupuncture group? inhibitor group and the warm acupuncture and inhibitor combined intervention group were significantly reduced(P<0.01);compared with the model group,the contents of BDNF? 5-HT?DA?NE?GC in the inhibitor group were not significantly different(P>0.05),the warm acupuncture group and warm acupuncture and inhibitor combined intervention group all increased to a certain extent(P<0.01);Compared with the warm acupuncture group,the inhibitor group and the warm acupuncture and inhibitor combined intervention group were significantly reduced(P<0.01).3 The effect of“Wen Shen Tong Du”Acupuncture Method on RAP1 signaling pathway in the depression model rats with kidney yang deficiency Western blotCompared with the normal group,the expression levels of MEK?ERK and CREB in the model group?warm acupuncture group?inhibitor group and the warm acupuncture and inhibitor combined intervention group did not change significantly(P>0.05),the expression levels of p-MEK?p-ERK?p-CREB ?RAF1 in which was significantly down-regulated(P<0.01),the expression levels of RAP1 and c AMP were down-regulated in the model group?inhibitor group and the warm acupuncture and inhibitor combined intervention group(P<0.01),and there was no significant difference in the expression levels of RAP1 and c AMP in the warm acupuncture group(P>0.05);Compared with the model group,the expression levels of MEK?ERK?CREB in the warm acupuncture group?inhibitor group and the warm acupuncture and inhibitor combined intervention group did not change(P>0.05),the expression levels of p-MEK?p-ERK?p-CREB?RAP1?RAF1 and c AMP in the inhibitor group were significantly down-regulated(P<0.01),and the expressions of p-MEK?p-ERK?p-CREB?RAP1?RAF1 and c AMP were significantly up-regulated in the warm acupuncture group(P<0.01),the expressions of p-MEK?p-ERK?p-CREB?RAP1 and c AMP in the warm acupuncture and inhibitor combined intervention group were all up-regulated to varying degrees(P<0.05 or P<0.01),and there was no significant difference in the expression of RAF1(P>0.05);Compared with the warm acupuncture group,the expression levels of MEK?ERK and CREB in the inhibitor group and the warm acupuncture and inhibitor combined intervention group did not change significantly(P>0.05),the expression levels of p-MEK?p-ERK?p-CREB?RAP1? RAF1?c AMP was significantly down-regulated(P<0.05 or P<0.01).Conclusion:1 Through combing the ancient literature,it is believed that the deficiency of kidney yang is the main pathogenesis of depression,and the method of warming the kidney and promoting yang plays a key role in the treatment of depression.2 Based on the theory of “acupoint sensitization”,explore the positive sensitization acupoints of the depression of kidney yang deficiency and the inner relationship between the acupoints,and draw the feasibility of the“Wen Shen Tong Du” acupuncture method to treat depression of kidney yang deficiency.3 Hydrocortisone hormone injection combined with chronic unpredictable mild stimulation can significantly inhibit the activation of the RAP1 signaling pathway,leading to weight loss?anhedonia and decreased ability of learning and memory in rats.4 “Wen Shen Tong Du”acupuncture can effectively improve the behavioral state of model rats,increase the weight and promote the recovery of learning and memory of rats.5 “Wen Shen Tong Du” acupuncture can activate the HPA axis,promote the release of GC,restore hippocampal function and increase the monoamine neurotransmitter 5-HT?DA?NE content,thereby improving depression-like behavior in rats.6 The“Wen Shen Tong Du”acupuncture method activates the RAP1 signaling pathway by up-regulating the expression of related proteins in the RAP1 signaling pathway,thereby achieving an antidepressant effect. |
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