摘要
Objective:To observe the antidepressant effect of Tongdu Qishen electroacupuncture method; To explore its mechanism of regulating the oxidative stress pathway of protein kinase C (PKC)/reduced coenzymeⅡ (NADPH) in depression model rats.Methods:Totally 32 SD rats were divided into control group, model group, Tongdu Qishen electroacupuncture group and escitalopram group according to random number table method, with 8 rats in each group. The model of depression was established by chronic unpredictable stress except control group. After the start of modeling, Tongdu Qishen electroacupuncture group was treated with electroacupuncture every day, 15 min/time/day; escitalopram group was given 30 mg/kg intragastric intervention. 1 day before the start of the experiment and the 28th day of the experiment, the growth of body mass was observed, and sugar preference experiment and open field experiment were performed. The protein expression levels of protein kinase C α (PKC α), p47phox, t and RAS related C3 botulinum toxin substrate 1 (Rac1) in hypothalamus were detected by Western blot, and the positive area ratio of NOX2 protein in hypothalamus was detected by immunofluorescence technique; ROS content in hypothalamus was detected using DCFH-DA fluorescent probe technique.Results:Compared with the model group, the Tongdu Qishen electroacupuncture group and the escitalopram group showed the body mass growth ( P<0.01) and sugar preference index increased ( P<0.01), and the moving distance ( P<0.05) and residence time ( P<0.01) in the central area of the open field experiment were longer; the protein expression levels of hypothalamic PKC α, p47phox and Rac1 decreased ( P<0.05 or P<0.01), the positive area ratio of NOX2 protein decreased ( P<0.05), and the level of ROS also decreased significantly ( P<0.01) in Tongdu Qishen electroacupuncture group and escitalopram group. Conclusion:Tongdu Qishen electroacupuncture group can improve the behavior of depressed rats, inhibit the oxidative stress response of PKC/NADPH pathway, and reduce the production of ROS, thereby reducing the brain damage caused by oxidative stress, and improving the symptoms of depression.
摘要
Objective To analyze the acupoint compatibility law and the application characteristics of acupuncture moxibustion treatment for depression based on complex network technology;To provide a basis and ideas for formulating prescriptions of acupuncture antidepressant therapy.Methods Related clinical literature about acupuncture for the treatment of depression was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Embase,Cochrane Library,and Web of Science from the establishment of the databases to 21st,Sep.2022.According to the inclusion and exclusion criteria,the literature was screened,and the clinical literature database of acupuncture in anti-depression was established.Excel 2010 was used for frequency analysis of acupoints.SPSS Modeler 18.0 was used for association rule analysis,and Gephi 0.9.5 was used for complex network analysis.Results Totally 579 articles were included,involving 172 acupoints,with a total frequency of 3 222.The results of descriptive analysis showed that the main meridians of acupoints were Governor Vessel,bladder meridian and liver meridian,and the specific acupoints such as Yuan-primary point,Shu-stream point,Back-shu point,Luo-connecting point,Eight confluence points,Front-mu point,He-sea point were frequently used.Association rules analysis showed that the combination of the highest correlation acupoints were"Yintang(GV29)-Baihui(GV20)".Through the complex network k-core analytic hierarchy process and community analysis,two core acupoint groups were finally obtained.The acupuncture angle,depth and direction were based on safety and meridian circulation direction,the tonifying and reducing method was based on syndrome differentiation,and the prescription was based on syndrome differentiation and symptomatic selection.Conclusion Acupuncture for depression has the following characteristics:the principle of acupoint selection is based on meridian selection and specific acupoints,the selection of core acupoints focuses on the treatment of spirit and the regulation of viscera,channels and functions,and the emphasis on syndrome differentiation and symptomatic acupoint selection in clinical treatment.While,it was important to pay more attention to the specificity of acupuncture and moxibustion.
摘要
Objective:To explore the effects of electroacupuncture(EA)on rats with chronic unpredictable mild stress(CUMS)-induced depression and proteins related to endoplasmic reticulum stress(ERS). Methods:Thirty-two Sprague-Dawley rats were randomly divided into a control group,a CUMS group,an escitalopram(ESC)group,and an EA group.Except for the control group,rats in other groups were exposed to CUMS.From the 1st day of modeling,the EA group was treated with EA at Baihui(GV20)and Yintang(GV29)every day,15 min each time;the ESC group was given intragastric intervention[ESC 10 mg/(kg·bw)every day],both for 28 d.Body mass measurement,open field test(OFT),and sucrose preference test(SPT)in each group were performed before(day 0)and after experiment(day 28)to record body mass growth,sugar preference index,and total distance and duration of central area in OFT.The protein expression levels of glucose-regulated protein 78(GRP78),caspase-12,and C/EBP homologous protein(CHOP)in the hippocampus and frontal cortex were detected by stain-free total protein normalization method of Western blotting.Meanwhile,the TdT-mediated dUTP-biotin nick end labeling assay was performed to determine the percentage of cell death in the frontal cortex. Results:After EA at Baihui(GV20)and Yintang(GV29),the body mass growth,sugar preference index,and total distance and duration of central area in OFT were effectively improved(P<0.05 or P<0.01);compared with the CUMS group,the expression levels of GRP78 and CHOP in the hippocampus,and caspase-12 and CHOP in the prefrontal cortex of rats were significantly reduced(P<0.05),and the apoptosis rate of cells in the prefrontal cortex decreased significantly(P<0.05). Conclusion:EA at Baihui(GV20)and Yintang(GV29)can significantly mitigate behavioral deficits of rats with CUMS-induced depression.The mechanism may be related to adjusting the ERS and inhibiting cell apoptosis.
摘要
Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.