【作者】 王丹妮；

【导师】 杨进；

【作者基本信息】 南京中医药大学 ， 中医临床基础， 2011， 博士

【摘要】 目的：以无症状HIV感染期为切入点,通过临床研究,探讨扶正排毒片的临床疗效,在此基础上通过测定相关免疫因子浓度,探讨扶正排毒片对无症状HIV感染者免疫功能的调节作用,观察是否存在免疫因子的差异及相关性,为临床诊断和治疗奠定基础,最终为无症状HIV感染者提供可以增强免疫、延缓发病进程的中药。方法：本研究分两部分进行。第一部分理论研究,从无症状HIV感染期称谓的由来及此称谓带来的歧义、无症状HIV感染期有症状、无症状HIV感染期有证可辨、中医药治疗艾滋病选择无症状HIV感染期的依据、无症状HIV感染期的中医药治疗进展、基于病因病机辨证治疗无症状HIV感染者共六个方面进行探讨。第二部分运用随机整群抽样、单盲平行对照研究方法,以临床症状、体征、免疫学指标(CD4+、CD8+细胞数以及CD4+/CD8+)、病毒载量、生存质量、血尿便常规、肝肾功能等为观察指标,选择符合入选标准的治疗组56例,对照组52例进行扶正排毒片对无症状HIV感染者的早期干预治疗。在此基础上运用流式细胞术、逆转录-聚合酶链反应(RT-PCR)、酶联免疫吸附试验法对疗效较好的32例进行CD4+、病毒载量及白细胞介素6、白细胞介素8、可溶性白细胞介素2受体、肿瘤坏死因子α、新喋呤、干扰素α浓度的测定,观察是否存在细胞因子的差异及相关性,探讨扶正排毒片对无症状HIV感染者免疫指标的调节作用。结果：1无症状HIV感染期有症状并且有证可辨,基于病因病机辨证的治疗为扶正排毒片对无症状HIV感染者的干预提供理论依据。2扶正排毒片对无症状HIV感染者的疗效研究显示：两组治疗后对无症状HIV感染者的症状体征总积分在a=0.05水准上具有统计学意义(P<0.05),治疗组的有效率和显效人数均明显高于对照组；两组治疗前后CD4+计数的变化没有统计学意义(P>0.05),但以CD4+计数上升或下降50/mm3为评定值计算有效率,两组治疗前和疗后6个月、疗后12个月的CD4+疗效比较均具有统计学意义(P<0.05),疗前和疗后3个月、疗后9个月的CD4+疗效比较没具有统计学意义(P>0.05),但治疗组的有效率明显高于对照组。随机抽取34例(总病例数的1/3,治疗组20例,对照组14例)无症状HIV感染者进行病毒载量检测,与疗前对比,两组疗后6个月和疗后12个月病毒载量疗效的差异在a=0.05水准上没有统计学意义(P>0.05),但治疗组的有效率高于对照组；两组治疗前后病毒载量变化的差异在a=0.05水准上没有统计学意义(P>0.05),但治疗组的病毒载量均数下降较多。通过扶正排毒片干预前后感染者生存质量量表分析,两组治疗前后对精力纬度、情感纬度、疼痛纬度、睡眠纬度积分在a=0.05水准上具有统计学意义(P<0.05),对躯体活动纬度、社会生活纬度积分疗后没有统计学意义(P>0.05),但疗后治疗组躯体活动纬度和社会生活纬度的积分较治疗前明显下降,且低于对照组的积分。扶正排毒片治疗前后安全性指标结果提示：未发现有肝肾功能的损害,未发现对血尿粪常规的不良影响,在临床上也未发现心电图、胸透的不良反应。3基于免疫激活相关分子的扶正排毒片干预无症状HIV感染者免疫调节机制研究显示：扶正排毒片治疗6个月后,无症状HIV感染者的IL-6、IL-8、TNF-α、NPI、IFN-α水平变化在a=0.05水准上具有统计学意义(P<0.05),而sIL-2R的水平变化在a=0.05水准上没有统计学意义(P>0.05)；无症状HIV感染者疗前IL-8、sIL-2R、TNF-α、NPI、IFN-α水平与健康对照组相比在a=0.05水准上均具有统计学意义(P<0.05),而无症状HIV感染者疗前IL-6水平与健康对照组相比在a=0.05水准上没有统计学意义(P>0.05)；除了TNF-α和IFN-α,各指标内部存在相关性,且呈正相关关系；各指标间NPI疗前与TNF-α疗后、NPI疗后与TNF-α疗后、IFN-α疗前与IL-8疗前、IFN-α疗前与IL-8疗后、CD4+疗前与sIL-2R疗前之间呈负相关关系；各指标间病毒载量疗前与sIL-2R疗前、病毒载量疗前与NPI疗后、病毒载量疗后与NPI疗前、病毒载量疗后与NPI疗后呈正相关系。结论：1中医药治疗艾滋病应把无症状HIV感染期作为切入点,针对病因病机辨证治疗。2扶正排毒片对无症状HIV感染者的症状体征的改善有着较好的效果,具有升高或稳定感染者CD4+计数的趋势,对部分病例具有降低病毒载量的作用,能从不同方面不同程度地提高了感染者的生存质量,临床用药安全。3本研究表明IL-8、sIL-2R、TNF-α、NPI、IFN-α与无症状HIV感染者密切相关,与其有关的细胞免疫参与其发病的全过程,可以作为了解无症状HIV感染者体内细胞免疫状态、治疗效果及预后判断的重要指标之一。4各指标内部存在一定相关性,各指标间存在一定相关性,但机制尚不明确,说明在扶正排毒片治疗无症状HIV感染者的作用机制中,上述指标间的关系有待进一步研究。5本研究表明IL-6、IL-8、TNF-α、NPI、IFN-α对判定中药治疗无症状HIV感染者的疗效有一定意义,可以作为中药疗效判定的参考指标之一。更多还原

【Abstract】 Objective:With asymptomatic HIV infectious period as the starting point, and through a more standardized clinical study, this research examines the clinical efficacy of Fuzheng Paidu Tablet. Based on this clinical study, we measured the concentration of associated immune factors, discussed the effect of Fuzheng Paidu Tablet in regulating the immune functions of asymptomatic HIV infection Patients, observed whether there are differences and correlation of the immune factor between the two, and established the theoretical foundation for the diagnosis and treatment. Finally we provided asymptomatic HIV carriers with Chinese materia medica preparations that can enhance immunity and delay the occurrence and progress of the disease.Methods:This research is divided into two parts. The first part is theoretical study. We discussed this from the following six aspects:the origin and ambiguity of asymptomatic HIV infectious period; symptoms in asymptomatic HIV infectious period; TCM symptoms types that can be differentiated in asymptomatic HIV infectious period; the reason of choosing HIV infectious patients in TCM treatment; advances in Chinese medicine treatment during asymptomatic HIV infectious period; treatment of asymptomatic HIV carriers based on etiology, pathogenesis and syndrome differentiation. In the second part cluster random sampling and Single-blind, parallel-group method were used. Outcome measures such as clinical symptoms and signs, immunological indexes (CD4+ cell count, CD8+ cell count and the ratio of CD4+/CD8+), viral load, quality of life, routine analysis of blood, urine and stool, liver Function and kidney function, etc. were observed. Altogether 56 cases in the treatment group met the inclusion criteria, and in the control group 52 cases did. CD4+ cell count, viral load, interleukin-6, interleukin-8, soluble interleukin-2 receptor, tumor necrosis factor-a, neopterin, interferon-a etc of the 32 patients with good clinical effect were measured. Observation was made on whether there are differences and correlation of the cell factor, and discussions were carried out on the moderating effect of Fuzheng Paidu Tablet to the asymptomatic HIV infection Patients’ Immunological indexes.Results:1 Symptoms existed and TCM symptoms type could be differentiated in asymptomatic HIV infectious period. Treatment of asymptomatic HIV infectious period based on etiology, pathogenesis and syndrome differentiation provided a theoretical foundation for the early intervention of Fuzheng Paidu Tablet to the patients during asymptomatic HIV infectious period.2 Research on the efficacy of Fuzheng Paidu Tablet to the patients in asymptomatic HIV infectious period indicated that there was statistical significance in the total score after treatment of the two groups at the significance level a=0.05. Effective rate and efficiently individual quantity were higher than that of the control group. There was no statistical significance in the change of CD4+ cell count of the two groups after the treatment. But to calculate the effectiveness by CD4+ cell count increase or decrease by 50/mm3, there is statistical significance between the data before treatment and 6 and 12 months after treatment. However, there was no statistical significance between the data before treatment and 3 and 9 months after treatment, but the efficacy of the treatment group was significantly higher than control group.34 patients in asymptomatic HIV infectious period were randomly selected (1/3 cases of the total number, including 20 patients of the treatment group and 14 patients of the control group) to measure viral load. Compared with the data before treatment, there was no statistical significance in viral load in 6 and 12 months after treatment of the two groups at the significance level a=0.05 (P>0.05), but the efficacy of the treatment was higher than the control group; there was no statistical significance on the change of viral load at the significance level a=0.05 (P>0.05),but the average of the viral load of the treatment group was markedly decreased. Analysis of the quality of life showed that there was statistical significance in the score of energy-latitude, emotional-latitude, pain-latitude, sleep-latitude (P<0.05), there was no statistical significance in the score of physical activity latitude and social life latitude (P> 0.05), but the score of the treatment group was obvious decreased than the score obtained before treatment and lower than the control group. Analysis of the safety indicator of Fuzheng Paidu Tablet found no damage to liver and kidney function, and no adverse effects to routine analysis of blood, urine and stool, and no adverse effects to electrocardiogram and chest X-ray fluoroscopy.3 The mechanism based on the immune activation related factors of the intervention to the immune regulation of Fuzheng Paidu Tablet showed that after 6 months of treatment, there was statistical significance on the change of IL-6, IL-8, TNF-a, NPI, and IFN-a at the significance level a=0.05(P<0.05), but no statistical significance in sIL-2R (P>0.05). Before treatment there was statistical significance in IL-8, sIL-2R, TNF-a, NPI, and IFN-a compared with the healthy control group (P<0.05), and before treatment, there was no statistical significance in IL-6 compared the healthy control group (P>0.05). Positive correlation exists between each indicator except TNF-αand IFN-α. There was negative correlation between NPI (before treatment) and TNF-α(after treatment), and also negative correlation between fellowing indicators:NPI (after treatment) and TNF-α(after treatment), IFN-α(before treatment) and IL-8 (before treatment), IFN-α(before treatment) and IL-8(after treatment), CD4+ (before treatment) and sIL-2R (before treatment). There was positive correlation between viral load (before treatment) and sIL-2R (before treatment), and also positive correlation between fellowing indicators:viral load (before treatment) and NPI (after treatment), viral load (after treatment) and NPI(before treatment), viral load (after treatment) and NPI (after treatment).Conclusion:1 Chinese medicine treatment for HIV/AIDS should take asymptomatic HIV infectious period as the starting point.2 Fuzheng Paidu Tablet can significantly improve the symptoms and signs of the patients during the asymptomatic HIV infection period, since this has a tendency to increase or stabilize the quantity of CD4 cell, and in some patients it can decrease the viral load, improve the quality of life from different levels and different aspects, and is safe in clinical use.3 This research suggests that there were close correlation between IL-8, sIL-2R, TNF-a, NPI, IFN-a and the symptom of the asymptomatic HIV infectious period. And cellular immunity correlated to those factors plays an important role in the whole process of the disease, and those factors can be important indicators of the cellular immunity condition and therapeutic effect and prognosis.4 There were correlations between each indicator, but the mechanism is unknown, and further research is needed on the mechanism of Fuzheng Paidu Tablet in the treatment of the patients during the asymptomatic HIV infection period.5 This resarch suggest that IL-6, IL-8, TNF-a, NPI, IFN-a have certain significance in determining the efficacy of Fuzheng Paidu Tablet in the treatment of the patients during the asymptomatic HIV infection period. And those factors can serve as important reference indexes.更多还原