Literature And Experimental Study Of The Liver Treatment Of Insomnia

ObjectiveInsomnia as a common disease of modern society, seriously affecting the quality of life.Western medicine focuses on the treatment of insomnia are sedative and hypnotic,but there are obvious side effects of Western medicine and the lack of long-term efficacy of evidence and lack of evidence of many prescription medicine efficacy. Clinically recurrent insomnia and abnormal emotions often accompany each other, and some herbs for insomnia studies showed indeed from the liver curative treatment of insomnia, insomnia tips from the liver has a certain clinical feasibility.In this study, from the onset of TCM and Western medicine perspective to find the theoretical basis from the liver insomnia, on the one hand the use of the system after the clinical effectiveness evaluation tools from the liver insomnia, insomnia is from the liver to find clinical evidence; On the one hand using electrophysiological and molecular biology analysis of treatment from the liver side effects insomnia targets for the treatment of insomnia from the liver to find laboratory evidence. Eventually be applied from the Liver clinical evidence-based theory of insomnia.Methods1Literature studyStudy Ⅰ:A comprehensive clinical research literature retrieved from the liver treatment of insomnia, the establishment of a randomized controlled clinical trial of the treatment of insomnia from the liver, quasi-randomized controlled clinical trials, self controlled trials, case reports, case analysis data base literature.Statistical quantities of each design type of clinical research for nearly20years annually.Study Ⅱ:Select a database study of randomized controlled trials and quasi-randomized controlled clinical trials on the treatment of insomnia from the liver to produce data to collect basic information mentioned in the table, design type, object of study, interventions, outcomes and other literature information, and the use of Cochrane risk of bias assessment tool for evaluating the quality of the literature.Study Ⅲ:According to accompany mental disorders, syndromes, intervention and control measures, outcome indicators will be included in the research literature is divided into two different subgroups, using RevMan5.0software in heterogeneous conditions allowed from the liver on the efficacy of treatment of insomnia meta-analysis.Study IV:Select a database study controlled trials from the liver after treatment of insomnia itself, making the data referred to collect basic information table, design type, object of study, interventions, outcomes and other literature information.According accompanied by mental disorders, syndromes,outcome measures will be included in the literature is divided into different subgroups,us ing RevMan5.0software in heterogeneous conditions allowed for the treatment of insomnia effects meta-analysis from the liver.2Experimental StudyStudy Ⅰ:Blank serum as control, were determined by HPLC from the liver side Sini serum containing natural ingredients, and compare four different batches of serum containing composition differences.Study Ⅱ:According to Springer protocol, using newborn SD rats within24h cultured cortical neurons, neuronal growth inverted phase contrast microscope to observe state and immunofluorescence techniques12d cells were cultured neurons identification.Study Ⅲ:SD primary cul tured rat cor t ical neurons cul tured million to7-12d, respectively, to join the control group, serum, Sini serum, serum final concentration of10%, continue to develop after3h and24h, using whole-cell patch clamp technique in each group GABA-induced IGABA, depicting the concentration-response curve, calculated IGABA decay time constant.Study IV:SD primary cul tured rat cortical neurons cultured million to7-12d, respectively, to join the control group, serum, serum Sini, spleen soup serum, serum at a final concentration of10%, were cultured for24h extraction of membrane proteins and total protein. Detected by western blot in each group GABAA receptor al, α2, α3, α5subunit content.Resul ts1Literature studyStudy I:The final study included977clinical literature from the liver treatment of insomnia, which accounted for randomized controlled clinical trials17.81%,quasi-randomized controlled clinical trials accounted1.23%, self controlled trials accounted for5.42%. From the liver of insomnia clinical research literature published from nine the number gradually increased to103in2013, which randomized/ quasi-randomized controlled clinical trials of28to2013from2003’s4, an increase of1993600%.Study II:Final included186from the liver insomnia random/quasi-randomized controlled clinical trial literature, the study of age, gender,concomitant diseases,syndromes can be a good representative of the distribution of the population prevalence of insomnia. From the random allocation method, allocation concealment, blinding application, determine the outcome of the loss in four areas,93.55%of the literature there is a high risk of bias.Study III:(1) Associated with menopause insomnia:liver qi stagnation, liver deficiency syndrome from the liver group scores lower than western medicine or medicine from his dirty set of governance.(2) Accompanied by insomniacs:liverqistagnation, stagnation of the fire permit from the liver group scores lower than western medicine or placebo.(3)Accompanied by depression,insomnia:No specific syndromes from the liver group scores lower than western medicine.(4) Accompanied by anxiety insomnia:No specific syndromes from the liver group scores lower than from his dirty Treating medicine group.(5) Primary insomnia: No specific syndromes from the liver combined with western medicine group or group scores lower than western medicine, traditional Chinese medicine theory of governance from his dirty or placebo; liver qi stagnation from the liver governance group scores lower than western medicine or medicine from his dirty Treating group; stagnation of the fire certificate less than western medicine group from the liver or combined western medicine group scores or Treating from his dirty medicine group; liver deficiency syndrome from the liver group scores lower than we stern medicine group or groups of governance from his dirty.(6) Unknown insomnia associated with mental illness:liver qi stagnation, stagnation of the fire permit from the liver group scores lower than western medicine or medicine from his dirty set of governance.Study IV:Final included111control trials, the study of the treatment of insomnia itself from the liver after age, gender, concomitant diseases, syndromes can be a good representative of the distribution of the population prevalence of insomnia. Compared with before treatment, scores were significantly lower in the subgroups from the Liver.2Experimental Study Study I:Relative retention time four Sini serum containing nine unique peaks of RSD were less than1%, with correlation coefficients above0.90, different batches of serum components proved relatively stable.But the relative peak area RSD up to61.041%, to prove the existence of differences between different batches of serum ingredients.Study Ⅱ:The class Ⅲ p-Tubulin antibody identified neurons in primary culture displayed a higher purity of cortical neurons. Microscope tips neuronal cultures to7-12d best activity, cell body plump, Halo obviously, evenly distributed, the initial formation of the neural network, suitable for patch clamp experiments.Study Ⅲ:After Sini after incubation in serum-containing drugs (1) Can enhance the affinity of GABA and GABAA receptors, with the extension of incubation time, the role has been weakened, but the GABAA receptor sensitivity to low concentrations of GABA are the enhancement.(2) May delay the GABAA receptor into inactivation. But with the extension of incubation time, the effect weakened.(3) The number of neurons in the cortex membrane GABA., receptors increase, and with prolonged incubation time, the role has been enhanced.Study IV:(1) After incubation in serum-containing drug Sini, cortical neurons in a1subunit total protein content was significantly increased, decreased significantly α5subunit content:cortical neuronal membrane proteins α2, α3subunits were significantly elevated, α5subunits were significantly decreased.(2) The spleen soup after incubation in serum-containing drugs, cortical neurons was significantly elevated total protein content of a1subunit, cortical neuronal membrane proteins α1, α3subunits were significantly increased, decreased significantly α5subunit content.(3) There are significant differences between the α1, α2subunit content Sini group and spleen soup group of membrane proteins in cortical neurons.Conclus ion1Literature studyCompared with the control group and the treatment of the former with the treatment of insomnia from the liver statistically significant improvement in some outcome measures, but because of lower methodological quality literature; intervention programs are not uniform; outcome indicators objectivity fuzzy qualitative indicators of poor standard, quantitative in dicators lack individual patient clinically important change assessment.Ultimately affect the results of the sub group meta-analysis of clinical significance explanation.From the liver to confirm the clinical effectiveness of the treatment of insomnia, and still need to carry out more high-quality multi-center, large randomized controlled clinical trials.2Experimental StudyFrom the liver side by enhancing GABAA receptor affinity for GABA; slow GABAA recept or in activation; enhance GABAA receptor expression on the cell membrane, enhance GABAA receptor-mediated mlPSP, played neuronal inhibition, there by may improve insomnia. From the liver side play sedative and hypnotic effects by increasing the total protein in neurons αl subunit content; through increased neuronal membrane proteina2, a3subunit content to play the role of anti-abnormal mood; neurons by reducing the total protein and membrane proteins the α5subunit content to avoid memory impairment. But away from the cell body functional status and mode of administration and differences insomatic cells, with the overall results still need to refer to each other confirmed.