目的:探讨健脾益气活血汤早期止血机制(,JYSD)治疗免疫性血小板病(ITP),方法:非药物治疗病例:选择健康志愿者作为正常对照组,与功能失调性子宫出血患者进行比较,胃肠道肿瘤出血和ITP,检测血液中5-羟色胺(5-HT)的变化,β-内啡肽(β-EP),血管活性肠肽(VIP),比较不同疾病症状患者血液神经递质的变化。药物治疗病例:根据随机对照多中心临床试验,将272例ITP患者随机分为三组:医治组(JYSD)结合组(JYSD+泼尼松)对比组(泼尼松)。血液神经递质(5-HT,β-EP,VIP)治疗前后检测外周血血小板(PLT)及分级评分。
结果:非药物治疗病例:与正常对照组比较,5-HT水平较高,ITP组VIP和β-EP水平均较低(P<0.001),还有5-HT,消化道肿瘤出血组的VIP和β-EP水平也低于正常对照组(P<0.05,0.001)。药物治疗病例:联合组和对照组治疗后PLT评分均低于治疗前(P<0.05、0.001)。3组患者治疗后PLT分级评分进行配对比较:3组中联合组最低,比治疗组好,但不优于对照组(与治疗组相比,P=0.005,与对照组相比,P=0.709)。全分析集(FAS)和每个方案集(PPS)的统计结果是一致的。治疗组和联合组的出血症状评分在治疗后7d开始下降。治疗后14d持续下降至研究结束(P<0.05)。另一方面,对照组在治疗后14d开始出现良好的效果(P<0.05)。FAS和PPS分析结果一致。在对照组中,治疗后5-HT水平较高,VIP水平较低,与治疗前比较(P<0.05,0.001)。治疗组和联合组治疗后β-EP水平均升高,与治疗前比较(P<0.05)。治疗后,治疗组和对照组的β-EP水平明显低于联合组(P<0.05)。治疗后,与对照组相比,治疗组和联合治疗组的VIP水平上调,经秩和检验,差异有统计学意义(P<0.01),并通过t检验(P=0.0002,0.0001)。
结论:泼尼松片在增加PLT水平方面优于JYSD,而强的松片联合JYSD在改善患者外周血PLT水平方面更具优势。然而,改善ITP患者的出血时间,与单一使用相比,两种药物的组合显着延迟,显示了中医药的特点和优势。JYSD可以通过脑-肠轴功能调节ITP患者的神经递质水平,动员ITP患者血液中的5-HT,促进血管和平滑肌的收缩,激活凝血机制是JYSD的早期止血机制。上调β-EP水平和平衡VIP水平可能是JYSD调节ITP患者免疫机制的重要组成部分。
OBJECTIVE: To explore the early hemostatic mechanism of Jianpi Yiqi Shexue decoction (, JYSD) in treating immune thrombocytopathy (ITP), based on the functional homeostasis of brain-intestine axis and blood neurotransmitter METHODS: Non-drug treatment cases: Healthy volunteers were selected as normal control group and compared with patients with dysfunctional uterine bleeding, gastrointestinal tumors with bleeding and ITP, to detect the changes of blood 5-hydroxytryptamine (5-HT), β-endorphin (β-EP), vasoactive intestinal peptide (VIP) and compare the changes of blood neuro-transmitters in patients with different disease symptoms. Drug treatment cases: According to the randomized controlled multicenter clinical trial, 272 ITP patients were randomly divided into three groups: treatment group (JYSD) combined group (JYSD + Prednisone) control group (Prednisone). The changes of blood neuro-transmitter (5-HT, β-EP, VIP) before and after treatment were detected on the basis of peripheral blood platelet (PLT) and grade score.
RESULTS: Non-drug treatment cases: compared with the normal control group, the 5-HT level was higher, and the VIP and β-EP levels were both lower in the ITP group (P < 0.001), and the 5-HT, VIP and β-EP levels in the Gastrointestinal tumors with bleeding group were also lower compared with the normal control group (P < 0.05, 0.001). Drug treatment cases: The PLT grading scores of the combination group and the control group after treatment were lower than that before treatment (P < 0.05, 0.001). The PLT grading score of the 3 groups were compared in pairs after treatment: the combination group was the lowest among the 3 groups, which was better than the treatment group, but no better than the control group (vs the treatment group, P = 0.005, vs the control group, P = 0.709). The statistical results of full analysis set (FAS) and per protocol set (PPS) were consistent. The bleeding symptom scores of the treatment and combination groups began to drop 7 d after treatment, and kept dropping 14 d after treatment until the end of the study (P < 0.05). On the other hand, the control group started to show favorable results 14 d after treatment (P < 0.05). The FAS and PPS analysis results were consistent. In the control group, the 5-HT level was higher and VIP level was lower after treatment, compared with those before treatment (P < 0.05, 0.001). The β-EP levels were both increased in the treatment and combination group after treatment, compared with those before treatment (P < 0.05). After treatment, the β-EP levels in the treatment and control groups were significantly lower compared with the combination groups (P < 0.05). After treatment, compared with the control group, the VIP levels in the treatment and combination groups were up-regulated, and the differences were statistically significant by rank sum test (P < 0.01), and by t-test (P = 0.0002, 0.0001).
CONCLUSIONS: The prednisone tablet is better than the JYSD in increasing the level of PLT, while prednisone tablet combined with JYSD has more advantages in improving patients\' peripheral blood PLT levels. However, in improving the bleeding time of ITP patients, the combination of the two drugs was significantly delayed compared with the single usage, showing the characteristics and advantages of traditional Chinese medicine. JYSD can regulate the neurotransmitter level of ITP patients through the function of the brain-gut axis, mobilize 5-HT in the blood of ITP patients to promote the contraction of blood vessels and smooth muscles, and activate the coagulation mechanism are the early hemostatic mechanisms of JYSD. Up-regulate the levels of β-EP and balancing VIP levels may be an important part of the immune mechanism of JYSD for regulating ITP patients.