| Purpose:Psychotropic Drugs are drugs with therapeutic effects on the central nervous system and affect mental activity.Patients with severe mental disorders need to take psychotropic drugs for long-term treatment,but these drugs generally have a series of obvious side effects,among which obesity is the most common side effect.Psychotropic drugs represented by olanzapine seriously affect the physical health and mental problems of patients,which is forming a vicious circle.It attempts to explore the mechanism of acupuncture and moxibustion therapy represented by press needles from two parts in the study:clinical trials and experimental studies.In clinical trials,acupuncture points on the waist and abdomen were used to treat obesity patients with Yang deficiency of spleen and kidney caused by olanzapine.The effect of the thumbtack needle acupuncture on the patient's weight,blood lipid level,metabolism-related hormones and mental symptoms was observed,and the application of the press needle to psychiatric diseases was evaluated.The clinical feasibility of the experiment,animal experiments aimed at the metabolism-related hormones and receptors,the influence of AMPK/SIRT1/PGC-1? metabolic pathways,and downstream metabolizing enzymes and the related proteins CPT,PPARy,UCP2 and other expressions were evaluated,moreover,in-depth exploration of the possible mechanism of action of thumbtack needle acupuncture therapy was conducted.It can provide early intervention for patients with Yang deficiency of spleen and kidney as the syndrome,or patients with obesity caused by the Yang deficiency of spleen and kidney as syndrome due to continuous application of psychotropic drugs,to propose a new idea of "consolidating the body and promoting vitality".The proposed method can maintain the physical and mental health of psychiatric patients,improve the compliance treatment from patient,and seek a convenient and effective treatment method,which can provide a theoretical basis for the application of thumbtack needle to treat obesity-induced side effects of psychotropic drugs.Materials and Methods:Part 1 Clinical trial1.Research objectFrom June 2018 to September 2018,the patients with obesity caused by antipsychotic drugs were recruited among inpatients in Shenyang Mental Health Center Hospital.With a detailed understanding on the medical history of patients,the physical examination,mental assessment scale,and psychiatric examination was conducted and the general patient data were collected.The patients who met the criteria for inclusion was included and patients who met in the exclusion criteria were excluded in the study.During the enrollment,the study subjects were enrolled according to the proportion of males and females,and a total of 64 patients with obesity caused by olanzapine who were 20 to 60 years old were included(4 cases were eliminated for the experiment could not be completed for some reason,and 60 cases' patient data were finally included.All clinical cases was collected and randomly divided into a thumbtack needle therapy group and a control group,with 32 cases in each group.2.Grouping and treatmentAll the collected clinical cases were randomly divided into the thumbtack needle group and the control group(which was equally divided between men and women)according to the male ward(30 cases)and female ward(30 cases).There were 30 cases included in the thumbtack needle group and the control group respectively.The patients of two groups participated in general rehabilitation activities and had the general hospitalized diet,who were trained the exercise education by the nurses.In the thumbtack needle acupuncture therapy group:in addition to general diet,exercise and education,the thumbtack needle was applied to the acupoints of abdomen and back for acupuncture,in total of 2 groups of acupoints.Group 1:acupoints of Tian Shu(double),Zhong Wan,Guan Yuan,Shen Shu(double)and Ming Men;Group 2:acupoints of Huaroumen(double),Xiawan,Qihai,Pishu(double)and Yao Yang Guan.First,the thumbtack needle was put into every acupoint of the Group 1 and leave the needles for 3 days;after removing the first group of acupoint acupuncture stickers,the acupoints of the second group were pierced by the thumbtack needles immediately,the needles were removed after leaving the needle for 3 days,resting for Id.The treatment of acupuncture points were conducted in the two groups alternately,and one group of acupoints was changed every 3 days.After 6 days of treatment,it rested for one day,and a total of 6 weeks of treatment ended.In the intervention of the control group:the ordinary tape was applied to the same acupoints as in the thumbtack needle acupuncture therapy group for 3 days in each group.The placebo-controlled treatment trials were conducted on the acupoints alternately between the two groups,which was rested for 1 day after application for 6 days,with a total of 6 weeks.3.Observation indicatorsA prospective randomized controlled method was used to evaluate the clinical efficacy of thumbtack needle therapy on the obese patients who was taking psychotropic drugs.The observation points were set up at 0 week and 6 weeks of intervention.(1)Main indicators:?Indicators related weight:body weight,body mass index(BMI),waist circumference(WC)?Adipokines:levels of leptin,adiponectin,insulin and homocysteine(2)Secondary indicators:?Blood lipid level:Total Cholesterol(TC),Triglycerides(TG),High Density Lipoprotein Cholesterol(HDL-C),Low Density Lipoprotein Cholesterol(LDL-C)?Symptom scale:PANSS scale,TESS scale and self-rating scale for constipation patients The effects on the body weight,lipid metabolism,mental symptoms and side effects of the patients were evaluated and observed with the above indicators.4.Statistical methodsThe experimental data were analyzed by SPSS22.0 statistical software.The measurement data were expressed as mean±standard deviation(x±s),and the number of count data was expressed as a percentage.A paired-sample t-test was used for comparison before and after treatment within the groups,the continuous data between the two groups were tested by an independent-sample t-test.Two-sided p<0.05 indicated that it was statistically significant difference.Part 2 Animal experiments1.Experimental animals and groupsThirty-two SPF healthy SD rats(which was half male and half male)were selected and randomly divided into a blank control group,a model control group,a thumbtack needle group and a metform in group,with 8 rats as half male and half male in each group.2.Grouping and intervention methods:Blank control group:Oral gavage of normal saline in dose of 10ml·kg-1,once a day for 28 consecutive days.Model control group:Oral gavage of olanzapine suspension in dose of 1.5 mg·kg-1.d-1,once a day for 28 consecutive days.Thumbtack needle group:Oral gavage of olanzapine suspension in dose of 1.5 mg·kg-1·d-1,once a day for 28 consecutive days.At the same time,the thumbtack needle acupuncture intervention should be conducted,the acupoints of Zhong Wan,Guan Yuan,Shen Shu(double),and Pi Shu(double)was selected.After the rat was fixed,the 0.15mm thumbtack needles were applied to the acupoints,the behavior of the rats were observed,and it should ensure that the needles are retained for 30 minutes,once a day,lasting for 28 consecutive days.Metformin group:Oral olanzapine suspension in dose of 1.5 mg·kg-1·d-1,once a day for 28 consecutive days.At the same time,the subjects were given metformin hydrochloride in dose of 200mg·kg-1·d-1.3.Sample collectionOne hour after the last intervention of drugs and acupuncture,the rats were intraperitoneally injected with 10%chloral hydrate solution in dose of 35ml·kg-1 in each group.After anesthesia,the abdominal wall of rat was opened,and 5 ml of whole blood was collected by abdominal aortic puncture,the separated serum was gained after leaving it to stand for 2 h.After the rats were sacrificed,abdominal adipose tissue was collected and stored in a refrigerator at-80? for later use.4.Indicator detectionThe weight of rats before and after the experiment was measured.The changes of serum lipids(triglycerides,cholesterol,high-density lipoprotein,low-density lipoprotein)was detected by colorimetric method in each group of rats;serum adiponectin and leptin levels was detected by ELISA method in each group of rats;the protein levels of AdipoRl,AdipoR2,PPARy and CPT1,as well as the expression levels of AMPK,SIRT1,PGC-1? and UCP-2 in the abdominal adipose tissue of rats in each group was detected by Western Blot method.5.Statistics and analysisAll experimental data were analyzed by spss 19.0 statistical software.The measurement data were expressed by±s,and the comparison between the groups was analyzed by one-way ANOVA,with bilateral P<0.05 as statistically significant.Result:Part 1 Clinical trial1.Weight related indicatorsBefore treatment,there were no significant differences among the two groups in body weight,BMI,and waist circumference(p>0.05).Compared with before treatment,the body weight and waist circumference of the patients in the thumbtack needle group were significantly reduced after treatment(p<0.05),which was statistically significant difference;while the weight and waist circumference of subjects did not change significantly after treatment in the control group(p>0.05),which was no statistical significance.Compared with the control group after treatment,the body weight and waist circumference of the subjects were significantly reduced after treatment(p<0.05)in the thumbtack needle group,with the statistically significant difference.However,there was no significant difference in BMI changes before and after treatment between the two groups and within the thumbtack needle therapy group(p>0.05).2.Comparison of blood lipid metabolism-related indicators:Before treatment,there was no significant difference in serum TG,TC,LDL-C,HDL-C and APOA1 between the push-acupuncture therapy group and the control group(p>0.05).Compared with before treatment,the serum levels of TG,TC,LDL-C,HDL-C,and APOA1 were significantly different between the two groups after treatment(p<0.05),with the statistically significant difference;after treatment,compared with the control groups,the serum levels of TG,TC,LDL-C,HDL-C,and APOA1were significantly different(p<0.05)in the thumbtack needle acupuncture therapy group,which was statistically significant.3.Adipokines and homocysteine:Before the treatment,the level of leptin,adiponectin,insulin,and homocysteine in the two groups of subjects was similar,and there was no significant difference between the two groups(p>0.05),indicating that the pre-treatment data were comparable in the two groups.After treatment,whether compared within the same group before treatment or between the two groups after treatment,there were significant differences in leptin,adiponectin,insulin and homocysteine(p<0.05).4.Evaluation of psychiatric symptoms and side effects:The total score of the PANSS scale and the score of the TESS scale between the two groups before treatment and after 6 weeks of treatment was shown no significantly statistical significance(p>0.05).However,in the negative symptom score of the PANSS scale subscale,the negative symptom score decreased after treatment compared with the score before treatment in the thumbtack needle acupuncture therapy group(p<0.05).Part 2 Animal experiments1.Body mass and blood lipid metabolism:After the model control group was modeled,the body mass increased significantly(p<0.01),the TC,TG,HDL-C and LDL-C was shown as typical abnormalities,and the lipid metabolism-related hormone was abnormal.Compared with the model control group,the body weight of the thumbtack needle group and the metformin group increased slowly(p<0.05),and TC,TG,HDL-C and LDL-C was maintained at normal levels compared with the blank control group,which was no obvious hormone change shown(p>0.05).2.Metabolism-related hormones and risk predictors:Compared with the blank control group,the contents of serum leptin,insulin and homocysteine in the other groups were significantly increased(p<0.01),and the content of adiponectin was significantly decreased(p<0.01),with the statistically significant difference;Compared with the model control group,the serum leptin,insulin,and homocysteine contents in the snap needle group and the metformin group were significantly reduced(p<0.01),and the adiponectin content was significantly increased(p<0.01).It was statistically significant;the serum leptin content of rats in the thumbtack needle group was higher than that of the metformin group(p<0.05),and the adiponectin content was lower than that of the metformin group(p<0.05),with the statistically significant difference.3 Expression of AdipoR1 and AdipoR2,PPARy,CPT1 in adipose tissue:compared with the blank control group,the expression levels of AdipoR1,AdipoR2,PPARy and CPT1 in the adipose tissue of rats were significantly reduced(p<0.01)in the remaining groups,with the statistically significant difference;compared with the model control group,the expression levels of AdipoR1,AdipoR2,PPARy,and CPT1 in the adipose tissue of rats in the thumbtack needle group and the metformin group were significantly increased(p<0.01),shown as the statistically significant difference;compared with the thumbtack needle group,the expression levels of AdipoR1,AdipoR2,PPARy,and CPT1 of the adipose tissue were significantly reduced(p<0.05)in the metformin group,which was the statistically significant difference.4 AMPK/Sirtl/PGC-1a signaling pathway related indicators and PPARy:AMPK,Sirtl,PGC-1?,UCP-2 and PPARy protein test results showed:there was no significant difference in the expression levels of AMPK and Sirtl of rat adipose tissue(p>0.05)in each group;compared with the blank control group,the expression level of p-AMPK,p-Sirtl,PGC-1? and UCP-2 in rat adipose tissue was significantly up-regulated(p<0.01)in the other groups,with the statistically significant difference;compared with the model control group,the expression levels of p-AMPK,p-Sirtl,PGC-1?,and UCP-2 in the adipose tissue of rats were significantly up-regulated in the thumbtack needle group and metformin group(p<0.01),with the statistically significant difference;compared with the thumbtack needle group,the expression levels of p-AMPK,p-Sirtl,PGC-1? and UCP-2 in the adipose tissue of the metformin group were significantly down-regulated(p<0.05),with the statistically significant difference.Conclusion:1.Thumbtack needle acupuncture at the acupoints in the waist and abdomen for strengthening corporeity and consolidating the body can reduce the weight of obese patients caused by olanzapine,improve blood lipid-related indicators,and regulate fat-related hormones to relieve patients' negative symptoms.It is feasible in psychiatric applications.2.Animal experiments have also verified the efficacy of thumbtack needle acupuncture points on the waist and abdomen.The mechanism may be through regulating the expression of PPARy protein;thereby it can improve the Yang deficiency of spleen and kidney in patients taking psychotropic drugs by regulating the AMPK/SIRT1/PGC-1? signaling pathway,to normalize the performance of lipid metabolism-related hormones,which could result to promote the lipid metabolism function of patient.3.Thumbtack needle acupuncture points on the waist and abdomen may have the effect of strengthening corporeity and consolidating the body,warming and transforming phlegm-damp,thereby it can consolidate the normal function of the body,improving the inherent Yang deficiency of spleen and kidney in patients with mental illness,which can prevent and treat the damage of spleen and kidney by toxic effects of psychotropic drugs. |
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