Integrated Research On Imaging And Diagnosis And Treatment Of Depression Based On Hypochlorous Acid Regulation

Depression is a mental disease with a very high incidence,and its low diagnosis rate and low cure rate lead to serious harm to people’s life,health and quality of life.The reason is that the current diagnosis of depression can only rely on a series of subjective test scales,lack of an objective gold standard;while the treatment methods have problems of poor efficacy,large side effects and high recurrence rate.Therefore,there is an urgent need to develop more reliable diagnostic criteria and effective treatments.Studies have shown that the lack of neurotransmitters dopamine(DA)and serotonin(5-HT)in the brain is an important cause of depression.In addition,the occurrence and development of depression is closely related to brain inflammation,resulting in a significant increase in the level of reactive oxygen species(ROS)such as hypochlorous acid(HCl O).Therefore,the down-regulation of neurotransmitter levels,the occurrence of high levels of ROS and neuroinflammation provide reliable targets and new ideas for the development of novel antidepressant diagnosis and treatment strategies and antidepressant drugs.At present,fluorescence imaging is a new method for real-time and in situ detection of the occurrence and development of diseases in the body.It has excellent properties such as noninvasiveness,high temporal,spatial resolution and deep tissue penetration.In recent years,it has been widely used in tumors,neurodegeneration,etc.Research on diagnosis and treatment of sexually transmitted diseases.However,the complexity and peculiarity of the brain structure make it difficult to develop drugs targeting the brain.Organic small molecule fluorescent materials have good chemical and photostability,easy to pass through the blood-brain barrier,relatively simple operation,brilliant biocompatibility and other advantages which is ideal material for the diagnosis and treatment of brain diseases.Based on the current problems in the field of depression diagnosis and treatment,this paper proposes a new antidepressant diagnosis and treatment strategy that integrates the release of neurotransmitters,antidepressant drugs,anti-inflammatory drugs,and antioxidants.A series of antidepressant fluorescent diagnostic reagents,MB-Rs,which are specifically triggered by hypochlorous acid to release neurotransmitters/antidepressants/anti-inflammatory substances,were developed.Using the fluorescence imaging ability of MB-Rs,the changes of HCl O levels in the mouse brain during the development of depression were observed,and the therapeutic effect of MB-Rs on depression was proved through behavioral tests and biochemical index analysis.This study successfully achieved the initial diagnosis and effective treatment of depression in mice,and provided a feasible new strategy and new material for the diagnosis and treatment of depression.The main contents of this paper are as follows:1.Three fluorescent diagnostic reagents,MB-Rs,were designed and synthesized,and their properties were characterized in detail.MB-Rs use methylene blue(MB),which has good antiinflammatory effect and excellent optical properties,as the fluorophore,and the specific recognition group of HCl O—urea bond—as the linking group to link MB and neurotransmitters(dopamine,serotonin)or antidepressants(fluoxetine),respectively.MB-Rs undergo deamidation reaction with HCl O to release MB with reduced inflammation and strong fluorescence,and the fluorescence recovery also releases DA/5-HT/fluoxetine(Flu)with antidepressant effect,respectively.The optical properties of MB-Rs were demonstrated by fluorescence spectroscopy and UV absorption spectroscopy.The release capacity of MB-Rs was characterized by high performance liquid chromatography(HPLC),and the in situ fluorescence imaging capability of MB-Rs in living cells was verified.This work provides an ideal material for further exploring the application of integrated diagnostic and therapeutic reagents in the diagnosis and treatment of depressed mice.2.To further explore the application of MB-Rs,a new diagnostic integrated reagent,in the evaluation of drug efficacy and the diagnosis and treatment of depressed mice.In vivo in situ fluorescence imaging results indicate that certain antidepressant drugs increase cellular oxidative stress and observe changes in HCl O levels in mouse brain during the development of depression.Through behavioral testing,biochemical index analysis,and comparison with the efficacy of common antidepressant drugs,it is shown that MB-Rs can effectively alleviate depressive behavior in mice by reducing inflammation,alleviating oxidative stress,and increasing neurotransmitters.In this work,the fluorescence changes before and after the reaction of MB-Rs with different concentrations of HCl O in the brain were used to successfully realize the preliminary diagnosis of depressed mice and the evaluation of the efficacy of antidepressant drugs,providing a feasible new strategy for the diagnosis and treatment of depression.new material.