Clinical Study On Evolution Of Insomniacs Characterized By Spleen Deficiency And Intervention Effect Of Bupiwei Xieyinghuo Shengyang Tang From Immune Inflammation

Objective1.By comparing the characteristics of cytokines in people with spleen-deficiency type of non-insomnia,insomniacs characterized by spleen deficiency,insomniacs characterized by spleen deficiency and stomach heat to explore the syndrome change characteristics of spleen-deficiency type of insomnia from the perspective of immune inflammation.2.To observe the clinical effect of Bupiwei Xieyinghuo Shengyang Tang on insomniacs characterized by spleen deficiency and stomach heat through regulating cytokines and to explore new ideas for the treatment of insomnia so as to expand its application scope.MethodsIn this study,insomniacs characterized by spleen deficiency and stomach heat were selected as research objects who were recruited from Guangdong Provincial Hospital of Traditional Chinese Medicine.The sleep quality and cytokine levels of the three groups were evaluated.The insomnia group with spleen deficiency and stomach heat was treated with Bupiwei Xieyinghuo Shengyang Tang for 28 days to evaluate the efficacy and safety before and after treatment,including the evaluation of changes in sleep quality and cytokine levels.ResultsStudy 1:Clinical Study on Evolution of Insomniacs characterized by Spleen Deficiency from Immune Inflammation1.sleep qualityThe PSQI of the non-insomnia group with spleen deficiency,the insomnia group with spleen deficiency and the insomnia group with spleen deficiency and stomach heat were respectively 5.12±1.65,13.78±2.14 and 13.70±2.48 points.2.serum cytokinesThe serum concentration of IL-1β difference were statistically significant(P<0.05)in the three groups and the trend was rise.And the insomnia group with spleen deficiency and stomach heat was significantly higher than the non-insomnia group with spleen deficiency on IL-1β(P＜0.05).The three groups had no statistical significance on serum IL-6、IL-1β、TNF-α、TNF-β and IL-10(P>0.05).But the three groups rendered into a rising trend on pro-inflammatory factor IL-1β、TNF-α and TNF-β.Moreover,the insomnia group with spleen deficiency was significantly higher than the insomnia group with spleen deficiency and stomach heat on pro-inflammatory factor IL-6(P<0.05).The two insomnia group were higher than the non-insomnia group on anti-inflammatory factor IL-10.The serum concentration of IFN-αdifference were statistically significant(P＜0.05)in the three groups and the trend was rise.Besides,the insomnia group with spleen deficiency and stomach heat was significantly higher than the other groups on IFN-α(P＜0.05).3.Correlation between cytokinesThere was no significant linear correlation between IL1β-IL6 in the three groups(P＞0.05).There was a significant linear positive correlation between IL1β-TNF α,IL1β-TNF β and TNF α-TNF β(P＜0.05).IL6—TNF α showed a significant linear negative correlation in the non-insomnia group(P＜0.05)and no significant linear correlation in the two insomnia groups(P>0.05).IL6-TNF β had no significant linear correlation in the non-insomnia group(P＞0.05)and a significant linear positive correlation in the two insomnia groups(P＜0.05).There was no significant linear correlation between TNF α-IL10 in the three groups(P＞0.05).There was no significant linear correlation between IL1 β-IL10 and TNF β-IL10 in both spleen deficiency groups(P＞0.05),and the insomnia group with spleen deficiency and stomach heat showed a significant linear positive correlation(P＜0.05).IL6-IL10 in all three groups showed a significant linear positive correlation(P＜0.05).The three groups of IL1 β-IFN α,TNF α-IFN α and TNF β-IFN α showed a significant linear positive correlation in the three groups(P＜0.05).IL6-IFN α had no significant linear correlation in the two spleen deficiency groups(P＞0.05),and a significant linear positive correlation in the insomnia group with spleen deficiency and stomach heat(P＜0.05).4.Correlation between total PSQI score and cytokinesThere was no significant linear correlation between the PSQI total scores and serum cytokine concentrations in the three groups(P>0.05).Study 2:Clinical Study Intervention Effect of Bupiwei Xieyinghuo Shengyang Tang from Immune Inflammation1.Efficacy evaluation:sleep quality(1)Subjective sleep qualityAfter 4 weeks of Treatment of Bupiwei Xieyinghuo Shengyang Tang,the total PSQI score,subjective sleep quality score,sleep latency score,sleep duration score,and total score of sleep medication use of insomniacs characterized by spleen deficiency and stomach heat were significantly lower than before treatment(P＜0.05).There was no significant difference in total score of habitual sleep efficiency,total score of sleep disorders and total score of daytime dysfunction compared with that before treatment.The total score of ISI decreased significantly compared with that before treatment(P＜0.05).There was no statistically significant difference in PSG total sleep time and sleep efficiency before treatment(P>0.05),but the sleep efficiency was on the rise trend.(2)Objective sleep qualityAfter 4 weeks of Treatment of Bupiwei Xieyinghuo Shengyang Tang,there was no significant difference in PSG items compared with that before treatment(P>0.05).The percentage of TST,WASO,NAW and N2 showed a downward trend compared with that before treatment.The LPS,SE,percentage of N1,N3 and REM showed an upward trend compared with that before treatment.2.Safety evaluation(1)Test and inspection indicatorsThe abnormal indicators in this study are mainly reflected in blood routine,liver function,second stool routine and ECG abnormalities.Among them,1 case had a decrease in white blood cell count,2 cases had a decrease in hemoglobin content,1 case had an increase in platelet count;4 cases had a slight increase in transaminase;2 cases had elevated urine occult blood,1 case had elevated urine white blood cells,1 case had elevated uric acid;Fecal occult blood increased;3 cases of sinus bradycardia,2 cases of sinus arrhythmia,and 1 case of occasional atrial premature beats.(2)Adverse eventsThere were no serious adverse events in the study.There were 2 mild adverse events in the study,both of which were gastrointestinal symptoms,and all recovered and improved before the end of the intervention.3.Effect mechanism:serum cytokinesAfter 4 weeks of treatment with Bupiwei Xieyinghuo Shengyang Tang,Il-1β,I1-6,Il-10 and TNF-α significantly increased compared with before treatment(P<0.05).There was no statistically significant difference in TNF-a and IFN-α compared with before treatment(P＞0.05),showing a decreasing trend.Conclusion1.Non-insomnia of spleen deficiency→insomnia of spleen deficiency type→insomnia of spleen deficiency and stomach heat type.With the development of insomnia and the change of insomnia syndrome types,patients show different and typical characteristics and changing trends in the symptoms of immune inflammation and cytokines level,and sleep quality is also correlated with the level of immune inflammation.Patients with spleen-deficiency insomnia present an activated state of immune inflammatory response,while patients with spleen-deficiency and stomach heat insomnia are in an overactive state of immune inflammation.2.Bupiwei Xieyinghuo Shengyang Tang has a obvious efficacy on patients with spleen-deficiency and stomach heat insomnia by improving subjective and objective sleep quality,especially sleep time,sleep duration,sleep rhythm,daytime spirit and etc.The sleep improvement effect of Bupiwei Xieyinghuo Shengyang Tang may achieve a relatively balanced inflammatory state in the body through increasing anti-inflammatory factor IL10 and pro-inflammatory factor IL1,IL6 and TNF.