PNS湿热证抗炎因子水平及黄葵胶囊的干预影响研究
|
摘要
目的
本研究依据肾病综合征湿热证与感染关系密切以及前人对湿热证的研究基础,选择原发性肾病综合征湿热证为对象,从分子生物学水平探讨观察原发性肾病综合征湿热证与血清抗炎因子IL-4、IL-10、IL-13的相关性,对促进和揭示原发性肾病综合征湿热证的实质、湿热病因部分病理机制及清热利湿中药的作用机制研究具有一定理论意义与应用价值。
方法
本课题主要采用前瞻性、随机对照的临床研究方法,应用双抗体夹心酶联免疫吸附法(ELISA法)和荧光定量PCR的实验检测方法,通过对原发性肾病综合征湿热证、非湿热证患者体内主要抗炎因子IL-4、IL-10、IL-13的水平检测,利用SPSS软件进行统计处理,系统分析肾病综合征湿热证与抗炎细胞因子IL-4、IL-10、IL-13水平的关系。再通过对原发性肾病综合征湿热证患者经清热利湿药物黄葵胶囊治疗四周后,观察湿热证与抗炎细胞因子水平的变化情况,及清热利湿药物黄葵胶囊治疗PNS湿热证的临床疗效,利用SPSS软件进行统计处理,综合分析湿热证与抗炎症因子的相关性,并进一步分析具有清热利湿功效的黄葵胶囊治疗原发性肾病综合征湿热证的作用及机理。
结果(一)PNS湿热证抗炎因子水平的实验研究
按纳入标准选取肾综湿热证患者40例,非湿热证患者20例,共60例。经统计学检验,两组在性别、年龄、病理资料方面无显著性差异(P>0.05),具有可比性。采用双抗体夹心酶联免疫吸附法(ELISA法)检测抗炎因子IL-4、IL-10、IL-13的水平,荧光定量PCR法检测外周血单个核细胞中IL-13mRNA表达。结果如下：
湿热证组患者体内的IL-4含量为45.67±8.27 pg/ml,高于非湿热证组患者体内的IL-4的含量32.73±9.01 pg/ml,经统计学检验有显著性差异(P<0.01)。
湿热证组患者体内IL-10含量为29.97±4.22 pg/ml,高于非湿热证组患者体内IL-10的含量19.45±4.71 pg/ml,经统计学检验有显著性差异(P<0.01)。
湿热证组患者体内IL-13含为25.92±6.94 pg/ml,高于非湿热证组患者体内IL-13的含量14.19±7.36 pg/ml,经统计学检验有显著性差异(P<0.01)。
湿热证组患者的外周血单个核细胞中IL-13mRNA水平为0.65±0.11,明显高于非湿热证组IL-13mRNA水平0.35±0.09,经统计学检验有显著性差异(P<0.05)。与湿热证IL-13水平升高表现相同。
湿热证组各患者的湿热证积分分别与IL-4、IL-10、IL-13含量相关性分析呈线性正相关(P<0.01)。
(二)黄葵胶囊干预对PNS湿热证临床及抗炎因子水平影响的研究
1、对症候的影响
用药前治疗组和对照组中医症状积分比较无显著性差异(P>0.05),具有可比性。治疗组疗后对水肿、咽喉肿痛、胸腹痞闷、口干不思饮、口苦、口中粘腻、小溲黄赤、大便粘滞症状有明显改善(P<0.05或P<0.01)。对照组疗后对水肿、口干不思饮、口苦、小溲黄赤、大便粘滞症状显著改善(P<0.01)。治疗后两组中医症状积分组间比较,治疗组对水肿、皮肤疖肿、疮疡、咽喉肿痛、胸腹痞闷、口苦、口中粘腻、小溲黄赤、大便粘滞的改善作用有显著性差异(P<0.05或P<0.01)。表明在改善中医症状方面,治疗组优于对照组。
2、对实验室指标的影响
湿热证经治疗后,治疗组和对照组患者比较,治疗组的活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、总胆固醇、甘油三脂、低密度脂蛋白及24h尿蛋白定量指标的改善优于对照组(P<0.05或P<0.01)。
3、对白细胞总数和超敏C反应蛋白的影响
湿热证经治疗后,治疗组和对照组患者血中白细胞总数和超敏C反应蛋白均有所下降,经统计学分析,与疗前比较仅治疗组的差异有显著性意义(P<0.05或P<0.01)；治疗后两组组间比较,治疗组的白细胞总数、超敏C反应蛋白均值的降低更显著(P<0.05或P<0.01)。
4、对抗炎因子水平的干预影响
治疗组疗后IL-4水平明显下降(30.02±8.22pg/ml),与治疗前水平(45.63±8.30pg/ml)相比,有显著性差异(P<0.01)。对照组疗前后比较无显著性差异(P>0.05)。治疗后两组组间比较,治疗组IL-4含量的下降水平明显高于对照组(P<0.01)。
治疗组疗后患者体内IL-10水平降低(19.21±4.78pg/ml),与治疗前水平(30.01±4.19pg/ml)相比,有显著性差异(P<0.01)。对照组疗前后比较无显著性差异(P>0.05)。治疗后两组组间比较,治疗组IL-10降低水平明显高于对照组(P<0.01)。
治疗组疗后IL-13水平显著下降(14.11±7.20pg/ml),与治疗前的水平(25.94±6.91pg/ml)相比,有显著性差异(P<0.01)。对照组疗前后比较无显著性差异(P>0.05)。治疗后两组组间比较,治疗组IL-13下降水平明显高于对照组(P<0.01)。
经药物治疗后,湿热证治疗组患者外周血单个核细胞中IL-13mRNA表达水平为0.34±0.06,明显低于对照组IL-13mRNA表达水平0.60±0.09,经统计学处理后,有统计学意义(P<0.05)。
治疗组患者治疗前后中医症状总积分差值分别与IL-4、IL-10、IL-13水平含量差值相关性分析呈线性正相关(P<0.05)。
结论
1、由PNS湿热证抗炎因子水平及黄葵胶囊干预对PNS湿热证抗炎因子水平影响的研究,结果显示原发性肾病综合征湿热证患者抗炎因子IL-4、IL-10、IL-13水平异常增高；原发性肾病综合征湿热证与抗炎因子水平的增高具有一定的相关性,湿热证症候积分分别与IL-4、IL-10、IL-13水平呈线性正相关。
2、由黄葵胶囊对PNS湿热证临床的干预影响结果显示：清热利湿黄葵胶囊具有下调原发性肾病综合征湿热证患者体内异常增高的抗炎因子水平的作用。
3、清热利湿药物黄葵胶囊能较好的缓解患者的湿热症状,改善肾综湿热证患者蛋白尿、高脂血症及高凝状态等,可提高肾综湿热证的临床疗效,减轻肾综病情,其作用机理可能与该药的抗炎、清除抗原等作用有关。
Objective
This study based on nephritic syndrome with damp-heat and infection close relationship and the predecessors of the research basis about damp-heat syndrome. From the molecular biology level, observed the relevance of Primary nephrotic syndrome(PNS) Damp-heat syndrome and anti-inflammatory cytokines IL-4, IL-10, IL-13. It has a certain theoretical meaning and application value for Primary nephrotic syndrome Damp-heat syndrome to revealed evidence of Damp-heat syndrome substantial, part of the pathogenesis and mechanism of Chinese medicine about clearing away heat and dampness.
Methods
The main subject of a prospective, randomized, controlled clinical research methods, applied double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) and fluorescence detection quantitative PCR experiments, through the primary nephritic syndrome damp, non-damp patients is the main anti-inflammatory factor IL-4, IL-10, IL-13 levels detected using the SPSS software to analyze the data, systems analysis nephritic syndrome damp-heat and anti-inflammatory cytokines IL-4, IL-10, IL-13 Levels. Then through the primary nephritic syndrome patients by clearing away heat and damp of drug capsules for four weeks treated by Huang Kui capsule, observed the change of damp-heat and anti-inflammatory cytokines and evaluated clinical efficacy clearing away damp-heat drug-Huang Kui Capsule in treatment of PNS with damp-heat syndrome Clinical. Use of SPSS software to analyze the data, comprehensive analysis of damp- heat syndrome and related anti-inflammatory factors, and further analysis of the efficacy of Huang Kui Capsule-clearing away damp- heat drug in treatment of primary nephritic syndrome with damp-heat syndrome about the effect and mechanism.
Result
1. PNS with damp-heat experimental study of anti-inflammatory cytokines
Select the kidney by the inclusion criteria 40 patients comprehensive damp-heat, non-damp-heat 20 patients, total 60 patients. The difference in the two groups in gender, age, pathological information was no significant difference(P>0.05), comparable. Double antibody sandwich enzyme-linked immunosorbent assay (ELISA) detection of anti-inflammatory factor IL-4, IL-10, IL-13 levels, quantitative PCR, peripheral blood monocyte cells of IL-13mRNA expression. The results are as follows:
(1)PNS with damp-heat patients the level of IL-4 was 45.67±8.27 pg/ml, higher than patients of non-damp-heat IL-4-32.73±9.01 pg/ml, the difference was statistically significant(P<0.01).
(2) PNS with damp patients the level of IL-10 was 29.97±4.22 pg/ml, higher than the patients of non-damp-heat IL-10-19.45±4.71 pg/ml, the difference was statistically significant(P<0.01).
(3)PNS with damp patients the level of IL-13 was 25.92±6.94 pg/ml, higher than the patients of non-damp-heat IL-13-14.19±7.36 pg/ml, the difference was statistically significant(P<0.01).
(4)PNS damp-heat patients peripheral blood monocyte cells of IL-13mRNA level of 0.65±0.11, significantly higher than non-damp-heat syndrome group IL-13mRNA level of 0.35±0.09, were statistically significant difference test (P<0.05).In comparison with PNS with damp-heat syndrome elevated levels of IL-13 was the same performance.
(5)The group PNS with damp- heat syndrome scores and the level of IL-4, IL-10, IL-13 were correlative (P<0.01).
2. Study the effect of Huang Kui Capsule on clinical and inflammatory cytokines in PNS with damp-heat symptoms
(1)The impact of the symptoms
Before treatment the comparison between the study group and the control group symptom score was not statistically significant (P>0.05). The study group after treatment edema, sore throat, distension and nausea in chest and belly, dry mouth and not think to drink, bitter mouth, sticky mouth, yellow red urine, sticky stool symptoms improved significantly (P<0.05 or P<0.01). After treatment, there was statistically significant difference between the study group and the control group in clinical symptoms (P<0.05 or P<0.01). These clinical symptoms were oedema, swelling of skin boils, sore, sore throat, distension and nausea in chest and belly, bitter mouth, sticky mouth, yellow red urine, sticky stool. That improve the clinical symptoms, the study group was better than the control group.
(2)The impact of laboratory test
Damp-heat syndrome after treatment, the difference between the study group and the control group about activated partial thromboplastin time (APTT), fibrinogen (FIB), total cholesterol, triglyceride, low density lipoprotein and 24h urinary protein indicators was better than the control group (P<0.05 or P<0.01).
(3)The impact of WBC total and hs-CRP
Damp-heat syndrome after treatment, the study group and the control group of patients with white blood cell count and high-sensitivity C-reactive protein were decreased, by statistical analysis, and in comparison with before treatment was significant only in the study group (P<0.05 or P<0.01);after treatment between the two groups, study group, the total number of leukocytes, high sensitive C-reactive protein more significantly reduced the mean (P<0.05 or P<0.01).
(4)The impact of inflammatory cytokines level
Study group, IL-4 levels after treatment were significantly decreased (30.02±8.22pg/ml), in comparison with before (45.63±8.30pg/ml), was significant (P<0.01). The control group before and after treatment showed no significant difference (P>0.05). Between the two groups after treatment, the study group IL-4 level decreased more significantly than control group (P<0.01).
Study group, IL-10 levels after treatment were significantly decreased (19.21+4.78pg/ml), in comparison with before (30.01+4.19 pg/ml), was significant (P<0.01). The control group before and after treatment showed no significant difference (P>0.05). Between the two groups after treatment, the study group IL-10 level decreased more significantly than control group (P<0.01).
Study group, IL-13 levels after treatment were significantly decreased (14.11±7.20pg/ml), in comparison with before (25.94±6.91pg/ml), was significant (P<0.01). The control group before and after treatment showed no significant difference (P>0.05). Between the two groups after treatment, the study group IL-13 level decreased more significantly than control group (P<0.01).
After drug treatment, the damp-heat syndrome group and in peripheral blood monocyte cells of IL-13mRNA expression level of 0.34±0.06, significantly lower than the control group, the expression of IL-13mRNA 0.60±0.09, after treatment was statistically significant(P<0.05).
The IL-4、IL-10、IL-13 levels difference between before and after treatment for patients respectively correlated linearly with the syndrome integral difference of Damp-heat syndrome patient in the study group (P<0.05).
Conclusion
1.The study PNS with damp-heat syndrome inflammatory cytokines treated by Huang Kui capsule, the results showed that patients with primary nephritic syndrome damp-heat inflammatory cytokines level IL-4, IL-10, IL-13 increased abnormally; primary nephritic syndrome with damp-heat and increased levels of inflammatory cytokines have close relationship, symptoms of damp-heat syndrome scores and the level of IL-4, IL-10, IL-13 correlative.
2. Used Huang Kui Capsule to treat of PNS with damp-heat syndrome the results showed that clearing away damp- heat drug Huang Kui Capsule adjusted down markedly inflammatory cytokines in PNS damp-heat syndrome patients with abnormal increase of inflammatory cytokines.
3. Clearing away damp- heat drugs Huang Kui capsule can better alleviate the symptoms of patients with damp-heat and improve proteinuria in patients with renal comprehensive damp-heat, hyperlipidemia, and hypercoagulable state, etc., could improve the clinical efficacy of comprehensive damp-heat in PNS patient, reduced kidney integrated disease, the mechanism may be related to the anti-inflammatory drug as the role of the antigen clearance.
本研究依据肾病综合征湿热证与感染关系密切以及前人对湿热证的研究基础,选择原发性肾病综合征湿热证为对象,从分子生物学水平探讨观察原发性肾病综合征湿热证与血清抗炎因子IL-4、IL-10、IL-13的相关性,对促进和揭示原发性肾病综合征湿热证的实质、湿热病因部分病理机制及清热利湿中药的作用机制研究具有一定理论意义与应用价值。
方法
本课题主要采用前瞻性、随机对照的临床研究方法,应用双抗体夹心酶联免疫吸附法(ELISA法)和荧光定量PCR的实验检测方法,通过对原发性肾病综合征湿热证、非湿热证患者体内主要抗炎因子IL-4、IL-10、IL-13的水平检测,利用SPSS软件进行统计处理,系统分析肾病综合征湿热证与抗炎细胞因子IL-4、IL-10、IL-13水平的关系。再通过对原发性肾病综合征湿热证患者经清热利湿药物黄葵胶囊治疗四周后,观察湿热证与抗炎细胞因子水平的变化情况,及清热利湿药物黄葵胶囊治疗PNS湿热证的临床疗效,利用SPSS软件进行统计处理,综合分析湿热证与抗炎症因子的相关性,并进一步分析具有清热利湿功效的黄葵胶囊治疗原发性肾病综合征湿热证的作用及机理。
结果(一)PNS湿热证抗炎因子水平的实验研究
按纳入标准选取肾综湿热证患者40例,非湿热证患者20例,共60例。经统计学检验,两组在性别、年龄、病理资料方面无显著性差异(P>0.05),具有可比性。采用双抗体夹心酶联免疫吸附法(ELISA法)检测抗炎因子IL-4、IL-10、IL-13的水平,荧光定量PCR法检测外周血单个核细胞中IL-13mRNA表达。结果如下：
湿热证组患者体内的IL-4含量为45.67±8.27 pg/ml,高于非湿热证组患者体内的IL-4的含量32.73±9.01 pg/ml,经统计学检验有显著性差异(P<0.01)。
湿热证组患者体内IL-10含量为29.97±4.22 pg/ml,高于非湿热证组患者体内IL-10的含量19.45±4.71 pg/ml,经统计学检验有显著性差异(P<0.01)。
湿热证组患者体内IL-13含为25.92±6.94 pg/ml,高于非湿热证组患者体内IL-13的含量14.19±7.36 pg/ml,经统计学检验有显著性差异(P<0.01)。
湿热证组患者的外周血单个核细胞中IL-13mRNA水平为0.65±0.11,明显高于非湿热证组IL-13mRNA水平0.35±0.09,经统计学检验有显著性差异(P<0.05)。与湿热证IL-13水平升高表现相同。
湿热证组各患者的湿热证积分分别与IL-4、IL-10、IL-13含量相关性分析呈线性正相关(P<0.01)。
(二)黄葵胶囊干预对PNS湿热证临床及抗炎因子水平影响的研究
1、对症候的影响
用药前治疗组和对照组中医症状积分比较无显著性差异(P>0.05),具有可比性。治疗组疗后对水肿、咽喉肿痛、胸腹痞闷、口干不思饮、口苦、口中粘腻、小溲黄赤、大便粘滞症状有明显改善(P<0.05或P<0.01)。对照组疗后对水肿、口干不思饮、口苦、小溲黄赤、大便粘滞症状显著改善(P<0.01)。治疗后两组中医症状积分组间比较,治疗组对水肿、皮肤疖肿、疮疡、咽喉肿痛、胸腹痞闷、口苦、口中粘腻、小溲黄赤、大便粘滞的改善作用有显著性差异(P<0.05或P<0.01)。表明在改善中医症状方面,治疗组优于对照组。
2、对实验室指标的影响
湿热证经治疗后,治疗组和对照组患者比较,治疗组的活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、总胆固醇、甘油三脂、低密度脂蛋白及24h尿蛋白定量指标的改善优于对照组(P<0.05或P<0.01)。
3、对白细胞总数和超敏C反应蛋白的影响
湿热证经治疗后,治疗组和对照组患者血中白细胞总数和超敏C反应蛋白均有所下降,经统计学分析,与疗前比较仅治疗组的差异有显著性意义(P<0.05或P<0.01)；治疗后两组组间比较,治疗组的白细胞总数、超敏C反应蛋白均值的降低更显著(P<0.05或P<0.01)。
4、对抗炎因子水平的干预影响
治疗组疗后IL-4水平明显下降(30.02±8.22pg/ml),与治疗前水平(45.63±8.30pg/ml)相比,有显著性差异(P<0.01)。对照组疗前后比较无显著性差异(P>0.05)。治疗后两组组间比较,治疗组IL-4含量的下降水平明显高于对照组(P<0.01)。
治疗组疗后患者体内IL-10水平降低(19.21±4.78pg/ml),与治疗前水平(30.01±4.19pg/ml)相比,有显著性差异(P<0.01)。对照组疗前后比较无显著性差异(P>0.05)。治疗后两组组间比较,治疗组IL-10降低水平明显高于对照组(P<0.01)。
治疗组疗后IL-13水平显著下降(14.11±7.20pg/ml),与治疗前的水平(25.94±6.91pg/ml)相比,有显著性差异(P<0.01)。对照组疗前后比较无显著性差异(P>0.05)。治疗后两组组间比较,治疗组IL-13下降水平明显高于对照组(P<0.01)。
经药物治疗后,湿热证治疗组患者外周血单个核细胞中IL-13mRNA表达水平为0.34±0.06,明显低于对照组IL-13mRNA表达水平0.60±0.09,经统计学处理后,有统计学意义(P<0.05)。
治疗组患者治疗前后中医症状总积分差值分别与IL-4、IL-10、IL-13水平含量差值相关性分析呈线性正相关(P<0.05)。
结论
1、由PNS湿热证抗炎因子水平及黄葵胶囊干预对PNS湿热证抗炎因子水平影响的研究,结果显示原发性肾病综合征湿热证患者抗炎因子IL-4、IL-10、IL-13水平异常增高；原发性肾病综合征湿热证与抗炎因子水平的增高具有一定的相关性,湿热证症候积分分别与IL-4、IL-10、IL-13水平呈线性正相关。
2、由黄葵胶囊对PNS湿热证临床的干预影响结果显示：清热利湿黄葵胶囊具有下调原发性肾病综合征湿热证患者体内异常增高的抗炎因子水平的作用。
3、清热利湿药物黄葵胶囊能较好的缓解患者的湿热症状,改善肾综湿热证患者蛋白尿、高脂血症及高凝状态等,可提高肾综湿热证的临床疗效,减轻肾综病情,其作用机理可能与该药的抗炎、清除抗原等作用有关。
Objective
This study based on nephritic syndrome with damp-heat and infection close relationship and the predecessors of the research basis about damp-heat syndrome. From the molecular biology level, observed the relevance of Primary nephrotic syndrome(PNS) Damp-heat syndrome and anti-inflammatory cytokines IL-4, IL-10, IL-13. It has a certain theoretical meaning and application value for Primary nephrotic syndrome Damp-heat syndrome to revealed evidence of Damp-heat syndrome substantial, part of the pathogenesis and mechanism of Chinese medicine about clearing away heat and dampness.
Methods
The main subject of a prospective, randomized, controlled clinical research methods, applied double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) and fluorescence detection quantitative PCR experiments, through the primary nephritic syndrome damp, non-damp patients is the main anti-inflammatory factor IL-4, IL-10, IL-13 levels detected using the SPSS software to analyze the data, systems analysis nephritic syndrome damp-heat and anti-inflammatory cytokines IL-4, IL-10, IL-13 Levels. Then through the primary nephritic syndrome patients by clearing away heat and damp of drug capsules for four weeks treated by Huang Kui capsule, observed the change of damp-heat and anti-inflammatory cytokines and evaluated clinical efficacy clearing away damp-heat drug-Huang Kui Capsule in treatment of PNS with damp-heat syndrome Clinical. Use of SPSS software to analyze the data, comprehensive analysis of damp- heat syndrome and related anti-inflammatory factors, and further analysis of the efficacy of Huang Kui Capsule-clearing away damp- heat drug in treatment of primary nephritic syndrome with damp-heat syndrome about the effect and mechanism.
Result
1. PNS with damp-heat experimental study of anti-inflammatory cytokines
Select the kidney by the inclusion criteria 40 patients comprehensive damp-heat, non-damp-heat 20 patients, total 60 patients. The difference in the two groups in gender, age, pathological information was no significant difference(P>0.05), comparable. Double antibody sandwich enzyme-linked immunosorbent assay (ELISA) detection of anti-inflammatory factor IL-4, IL-10, IL-13 levels, quantitative PCR, peripheral blood monocyte cells of IL-13mRNA expression. The results are as follows:
(1)PNS with damp-heat patients the level of IL-4 was 45.67±8.27 pg/ml, higher than patients of non-damp-heat IL-4-32.73±9.01 pg/ml, the difference was statistically significant(P<0.01).
(2) PNS with damp patients the level of IL-10 was 29.97±4.22 pg/ml, higher than the patients of non-damp-heat IL-10-19.45±4.71 pg/ml, the difference was statistically significant(P<0.01).
(3)PNS with damp patients the level of IL-13 was 25.92±6.94 pg/ml, higher than the patients of non-damp-heat IL-13-14.19±7.36 pg/ml, the difference was statistically significant(P<0.01).
(4)PNS damp-heat patients peripheral blood monocyte cells of IL-13mRNA level of 0.65±0.11, significantly higher than non-damp-heat syndrome group IL-13mRNA level of 0.35±0.09, were statistically significant difference test (P<0.05).In comparison with PNS with damp-heat syndrome elevated levels of IL-13 was the same performance.
(5)The group PNS with damp- heat syndrome scores and the level of IL-4, IL-10, IL-13 were correlative (P<0.01).
2. Study the effect of Huang Kui Capsule on clinical and inflammatory cytokines in PNS with damp-heat symptoms
(1)The impact of the symptoms
Before treatment the comparison between the study group and the control group symptom score was not statistically significant (P>0.05). The study group after treatment edema, sore throat, distension and nausea in chest and belly, dry mouth and not think to drink, bitter mouth, sticky mouth, yellow red urine, sticky stool symptoms improved significantly (P<0.05 or P<0.01). After treatment, there was statistically significant difference between the study group and the control group in clinical symptoms (P<0.05 or P<0.01). These clinical symptoms were oedema, swelling of skin boils, sore, sore throat, distension and nausea in chest and belly, bitter mouth, sticky mouth, yellow red urine, sticky stool. That improve the clinical symptoms, the study group was better than the control group.
(2)The impact of laboratory test
Damp-heat syndrome after treatment, the difference between the study group and the control group about activated partial thromboplastin time (APTT), fibrinogen (FIB), total cholesterol, triglyceride, low density lipoprotein and 24h urinary protein indicators was better than the control group (P<0.05 or P<0.01).
(3)The impact of WBC total and hs-CRP
Damp-heat syndrome after treatment, the study group and the control group of patients with white blood cell count and high-sensitivity C-reactive protein were decreased, by statistical analysis, and in comparison with before treatment was significant only in the study group (P<0.05 or P<0.01);after treatment between the two groups, study group, the total number of leukocytes, high sensitive C-reactive protein more significantly reduced the mean (P<0.05 or P<0.01).
(4)The impact of inflammatory cytokines level
Study group, IL-4 levels after treatment were significantly decreased (30.02±8.22pg/ml), in comparison with before (45.63±8.30pg/ml), was significant (P<0.01). The control group before and after treatment showed no significant difference (P>0.05). Between the two groups after treatment, the study group IL-4 level decreased more significantly than control group (P<0.01).
Study group, IL-10 levels after treatment were significantly decreased (19.21+4.78pg/ml), in comparison with before (30.01+4.19 pg/ml), was significant (P<0.01). The control group before and after treatment showed no significant difference (P>0.05). Between the two groups after treatment, the study group IL-10 level decreased more significantly than control group (P<0.01).
Study group, IL-13 levels after treatment were significantly decreased (14.11±7.20pg/ml), in comparison with before (25.94±6.91pg/ml), was significant (P<0.01). The control group before and after treatment showed no significant difference (P>0.05). Between the two groups after treatment, the study group IL-13 level decreased more significantly than control group (P<0.01).
After drug treatment, the damp-heat syndrome group and in peripheral blood monocyte cells of IL-13mRNA expression level of 0.34±0.06, significantly lower than the control group, the expression of IL-13mRNA 0.60±0.09, after treatment was statistically significant(P<0.05).
The IL-4、IL-10、IL-13 levels difference between before and after treatment for patients respectively correlated linearly with the syndrome integral difference of Damp-heat syndrome patient in the study group (P<0.05).
Conclusion
1.The study PNS with damp-heat syndrome inflammatory cytokines treated by Huang Kui capsule, the results showed that patients with primary nephritic syndrome damp-heat inflammatory cytokines level IL-4, IL-10, IL-13 increased abnormally; primary nephritic syndrome with damp-heat and increased levels of inflammatory cytokines have close relationship, symptoms of damp-heat syndrome scores and the level of IL-4, IL-10, IL-13 correlative.
2. Used Huang Kui Capsule to treat of PNS with damp-heat syndrome the results showed that clearing away damp- heat drug Huang Kui Capsule adjusted down markedly inflammatory cytokines in PNS damp-heat syndrome patients with abnormal increase of inflammatory cytokines.
3. Clearing away damp- heat drugs Huang Kui capsule can better alleviate the symptoms of patients with damp-heat and improve proteinuria in patients with renal comprehensive damp-heat, hyperlipidemia, and hypercoagulable state, etc., could improve the clinical efficacy of comprehensive damp-heat in PNS patient, reduced kidney integrated disease, the mechanism may be related to the anti-inflammatory drug as the role of the antigen clearance.
引文
[1]蒋燕.疏风宣肺对肾病湿热证干预作用的思考[J].辽宁中医杂志,2005；32(4)：291-292.
[2]李志更,王天芳,赵燕,等.慢性肾功能衰竭常见证候与证候要素的现代文献分析比较[J].中华中医药学刊,2007；25(1)：52-53.
[3]孙伟,曾安平,严志林,等.湿热病邪与慢性肾病关系探讨：附152例临床资料分析[J].中医研究,2000；13(1)：36-37.
[4]沈庆法.中医肾脏病学[M].上海：上海中医药大学出版社,2008,53-54.
[5]周恩超.“肾实证”分类考辨[J].江苏中医药,2004；25(12)：5-6.
[6]陈以平,邓跃毅,张春菘.肾病的辨证与辨病治疗[M].北京：人民卫生出版社.2003,47.
[7]戴京璋.实用中医肾病学[M].北京：人民卫生出版社.2002,118.
[8]陈以平.湿热病邪与新月体肾炎[J].江苏中医药,2006；27(6)：3-4.
[9]时振声.时氏中医肾脏病学[M].北京：中国医药科技出版社,1997,1.
[10]沈庆法.肾病湿热证的研究[J].浙江中医学院学报,2000；24(1)：39.
[11]柳丛,饶向荣,李秀英,等.78例慢性肾脏病患者血瘀证与肾小管-间质病理损伤的相关性分析[J].中国中西医结合肾病杂志,2008；9(3)：251-253.
[12]李志更,王天芳,赵燕,等.慢性肾功能衰竭常见证候与证候要素的现代文献分析比较[J].中华中医药学刊,2007；25(1)：52-53.
[13]李晓政,闫彩香.代谢综合征及2型糖尿病慢性肾损害湿热血瘀证的相关研究[J].中国中医药科技,2007；14(6)：385-386.
[14]熊玮,王小琴,郭向东,等.慢性肾炎中医证候分布规律研究[J].临床肾脏病杂志,2008；8(3)：131-133.
[15]严志林,孙伟,等.湿热与原发性肾小球疾病关系的临床分析[J].湖北中医杂志,2005；27(10)：12-13.
[16]陈香美,陈以平,李平,等.1016例IgA肾病患者中医证候的多中心流行病学调查及相关因素分析[J].中国中西医结合杂志,2006；(26)3：197-201.
[17]桂泽红,马俊杰,邹川,等.50例肾移植受者中医证候特点分析[J].辽宁中医杂志2007；34(12)：1676-1677.
[18]邵光新,王亿平,曹恩泽,等.500例慢性肾功能衰竭中医证候特点分析[J].中华实用中西医杂志,2007；20(1)：994-995.
[19]阳晓,朱文锋,周小舟,等.慢性肾衰患者不同阶段病机证候特点临床分析[J]·中医杂志,2000；41(6)：350-352.
[20]余江毅,熊宁宁,余承惠.慢性肾病瘀血与湿热病理的临床和实验研究[J].辽宁中医杂志,1995；22(2)：91-92.
[21]王丽萍,陈建,庄永泽.IgA肾病湿热证与临床病理的相关性研究[J].中华中医药学刊,2008；26(1)：178-180.
[22]熊国良,李顺民,易铁钢,等.尿检异常IgA肾病湿热证微观指标的研究[J].中国医师杂志,2007；9(11)：1534-1535.
[23]李玲.肾病湿热浅析[J].中国中医急症,2007；16(2)：184-185.
[24]阮诗玮,郑敏麟,王智,等.IgA肾病湿热证与肾穿刺活检病理组织关系的临床研究[J].中国中西医结合肾病杂志,2003；4(10)：583-584.
[25]朱辟疆,韦先进,江丽萍,等.慢性肾小球疾病尿细胞因子改变及其与中医证型的关系[J].现代中西医结合杂志,2005；14(1)：20-22.
[26]朱辟疆,周逊,赵华等.慢性肾功能衰竭微炎症状态与中医证型关系研究[J].现代中西医结合杂志,2008；17(5)：652-654.
[27]吴仕九,廖礼兵.湿热证大鼠肾内髓及尿液中水通道蛋白AQP2含量的变化[J].中国中医药科技,2003；10(1)：4-5.
[28]王亿平,茅燕萍,曹恩泽,等.清肾颗粒对慢性肾功能衰竭急剧加重湿热证患者肿瘤坏死因子及其受体的干预作用[J].中国中西医结合急救杂志,2006；13(3)：135-138.
[29]解汝娟,晋青,那士平.C-反应蛋白和肿瘤坏死因子与慢性肾功能衰竭[J].中国康复医学.2003；7：3023-3024.
[30]周莺,李俊彪,伍新林,等.丹芍汤对慢性原发性肾小球疾病尿IL-6水平的影响[J].中国中医药信息杂志,2003；10(1)：12-14.
[31]盛梅笑.孙伟.贾宁人,等.肾炎湿热证血清sICAM—1变化的临床观察[J],辽宁中医杂志,2003；30(11)：891-892.
[32]朱辟疆,施荣华,刘永平.慢性肾小球疾病湿热证血浆及尿白介素-6(IL-6)的改变[J].浙江中西医结合杂志,1999；9(2)：75.
[33]邸若虹,李永健,童瑶.湿热证“正盛邪实”病机浅探[J].中医药学刊,2004；22(1)：106-109.
[34]焦钦安.从湿热毒论治IrA肾病[J].福建中医药,2004；35(4)：55-56.
[35]张大宁,沈伟梁,张勉之,等.“肾虚血瘀·湿热论”与港、澳地区慢性肾炎发病关系的研究[J].中国中医基础医学杂志,2003；9(6)：401-403.
[36]张琪.张琪临床经验辑要[M].北京：中国医药科技出版社,1998,49-62.
[37]傅文录.时振声辨治肾病湿热证经验[J].中医研究,1995；8(3)：24.
[38]卢远航.以湿热论治肾病综合征191例[J].陕西中医,1998；19(10)：439-440.
[39]方小南.龙胆泻肝汤加减治疗难治性肾病综合征18例疗效观察[J].中国中医基 础医学杂志,2002；8(8)：60.
[40]刘建国.中西医结合治疗难治性肾病的良方妙法[M].北京：中国医药科技出版社,2000,138.
[41]黄国东,何小萍,向少伟,等.清热利湿活血法治疗隐匿型IgA肾病的临床观察[J].吉林中医药,2007；27(10)：11-14.
[42]何小萍.论清利湿热法是原发性肾小球疾病的重要治法[J].河南中医药学刊,2002；17(3)：77.
[43]刘宝厚,甘培尚,杨扬.肾复康1号颗粒治疗慢性肾小球肾炎临床疗效观察[J].中国中西医结合肾病杂志,2004；5(10)：583-584.
[44]吴立友,饶家珍,赖申昌.等.肾衰方治疗慢性肾衰竭湿热证的临床研[J].时珍国医国药,2007；18(1)：175-176.
[45]李聃丹,刘小菁,陶冶.肾病综合征患者血清sCD40L与血脂水平相关性研究[J].西部医学,2006；18(2)：137-138.
[46]张小妮,金敏.小儿肾病综合征与CuZn-SOD、GSH-Px及MDA的相关性研究[J].甘肃医药,2008；27(2)：10-12.
[47]李苗苗.血清FT3、FT4浓度变化与肾病综合征的关系[J].中国现代药物应用,2009；3(2)：106.
[48]付瑶,潘晓芳.不同程度尿蛋白患者血清甲状腺激素水平变化及其临床意义[J].医学与哲学(临床决策论坛),2009；30(1)：36-37.
[49]黄慧.肾病综合征患者血IL-8水平变化及其临床意义[J].常州实用医学,2008；24(5)：300-301.
[50]张洪亚,张平,高泉.肾病综合征患者血IL—8与尿IL—8水平测定的临床意义[J].淮海医药,2003；21(6)：444-445.
[51]常月琴,周成林.肾病综合征患者血和尿IL-8测定的临床意义[J],江苏大学学报(医学版),2006；16(3)：251-252.
[521李宇颖,刘素雁,刘晓刚.原发性肾病综合征患者血清IL-2、IL-13的研究[J].哈尔滨医科大学学报,2005；39(2)：190-193.
[53]胡昭,江蓓,郭齐,等.原发性肾病综合征患者治疗前后血及尿IL-8、IL-13水平测定及其临床意义[J].山东医科大学学报,2002；40(1)：70—71.
[54]邓颖敏.高岩肾病综合征患儿外周血单个核细胞核因子-KB活性水平观察[J].实用医学杂志,2006；22(1)：49-50.
[55]刘宏伟.肾病湿热证的实验研究进展[J].中国中医基础医学杂志[J].1995；1(4)：35.
[56]孙伟,曾安平,严志林,等.湿热病邪与慢性肾病关系探讨：附152例临床资料分析[J].中医研究2000；13(1)：36-37.
[57]侯安会,王磊.肾病湿热探讨[J].黑龙江中医药,2000；(1)：5.
[58]陈伊伦,张华滋,陈文清.肾病综合征感染并发症防治探讨[J].浙江医学,2007；29(4)：363-406.
[59]刘芸芳,彭小梅,唐盛.成人肾病综合征医院感染的临床分析[J].现代中西医结合杂志,2008；17(32)：5000-5001.
[60]文细毛,任南,徐秀华,等.全国医院感染监控网医院感染病原菌分布及耐药性分析[J].中华医院感染学杂志,2002；12(4)：241-224.
[61]张友道,叶任高,李幼姬.成人原发性肾病综合征临床及实验系列研究[J].医学研究通讯,2001；30(1)：18-19.
[62]刘刚,章友康,谌贻璞.肾病综合征的常见并发症[J].临床肾脏病杂志,2008；8(4)：183-184.
[63]沈庆法.肾脏病湿热证的研究(续)[J].浙江中医学院学报,2000；24(2)：15.
[64]谢桂权,高颖,冯天保,等.清热利湿法治疗肾病综合征湿热证45例疗效观察[J].新中医,2007；39(10)：85-87.
[65]伊娜.曹式丽治疗老年原发性肾病综合征感染并发症的经验[J].辽宁中医杂志,2008,36(8)：1135-1136.
[66]张淑君.益气养阴利湿热法治疗肾病综合征30例[J].实用中医内科杂志,2007；21(7)：62.
[67]李永伟,李棱彪,扬宏志,等.原发性肾病综合征(PNS)患者血清IL-6、IgG水平与中医分型的相关性[J].中国中医药信息杂志,2001；8(6)：47-48.
[68]聂莉芳.肾病湿热证辨治刍议[J].江苏中医药,2006；27(6)：9.
[69]安辉.肾病综合征难治因素的分析[J].湖北中医学院学报,2004；6(2)：42-44.
[70]Pinsky MR. Dysregulation of the immune response in severe sepsis. Am J Med Sci,2004; 328(4):220-229.
[71]刘江文.炎性细胞因子和外科感染[J].华西医学,2003,18(2)：274-275.
[72]赵有成,魏宏建,段勇.重症感染者血中IL26和TNF2α检测的意义[J].中国抗感染化疗杂志.2003；3(5)：315-317.
[73]Arend W P. Interleukin 1 receptor antagonist:A new member of the interleukin 1 family. J Clin Invest,1991; 88(5):1445.
[74]李君蕊,赵宝春,辛桂荣.抗炎因子与感染的关系研究进展[J].中国煤炭工业医学杂志,2008；11(2)：268-270.
[75]Hart P H, Vitti G F, Burgess D R, et al. Potential antiinflammatory effects of interleukin 4:suppression of human monocyte tumor necrosis factor alpha, interleukin 1 and prostaglandin E2. Natl Acad Sci USA,1989; 86(10):3 803.
[76]Te Velde A A, Hui jbens R J F, Hei je K, et al. Inter-leukin-4 inhibits secretion of IL-1β, tumor necrosis factor a and IL-6 by human monocytes. Blood,1990; 76(7):1392. Standiford T J, Strieter R M, Chensue S W, et al. IL-4 inhibits the expression of IL-8 from stimulated human monocytes. J Immunol,1990; 145(5):1 435.
[77]Al-Ramadi B K, Meissler J J, Huang D, et al. Imm-unosuppression induced by nitric oxide and its inhibition by interleukin-4. Eur J Immunol,1992; 22(9):2 249.
[78]Jenkins J K, Arend W P. Interleukin 1 receptor anta-gonist production in human monocytes is induced by IL-1 αlpha, IL-13, IL-4 and GM-CSF. Cytokine,1993; 5(5):407.
[79]Corcoran M L, stetler-Stevenson W G, Brown P D, et al. Interleukin 4 inhibition of prostaglandin E2 synthesis blocks interstitial collagenase and 92-KDa type IV collagenase/gelatinase production by human monocytes. J Biol Chem,1992; 267(1):515.
[80]Hiester A A, Metcalf D R, Campbell P A. Interleu-kin-4 is chemotactic for mouse macrophages. Cell Immunol,1992; 139(1):72.
[81]Beckmann M P, Cosman D, Fanslow W, et al. The interleukin-4 receptor: structure, function, and signal transduction. Chem Immunol,1992; 51(1):107.
[82]Gharee-Kermani M. Phan SH. Role of eytokines and eytokine therapy in wound healing and fibrotic disease Curr Pharm Des,2001; 7,1083-1087.
[83]齐文杰,任爱民,张淑文,等.血清促炎因子、抗炎因子在急性感染患者中的动态变化及中药干预的影响[J].中国中西医结合杂志,2000；20(11)：824—827.
[84]Majori M, Caminati A. Predominant TH1 cytokine pattern in peripheral blood from subjects with chronic obstructive pulmonary disease[J]. J Allergy ClinImmunol,1999; 103(3 pt 1):458-462.
[85]周道远,李幼姬,王俭勤,等.干扰素-γ和白细胞介素4对狼疮肾炎患者巨噬细胞炎症蛋白-1α产生的效应[J].中华肾脏病杂志,2002；18(1)：25-28.
[86]Del Prete G, De Carli M, Almerigogno F, et al. Human IL-10 is produced by both type 1 helper (Thl) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol,1993;150(2):353.
[87]De Wall Malefyt R, Abrams J, Bennett B, et al. Interleukin 10(IL-10)inhibits cytokine synthesis by human monocytes:An autoregulatory role of IL-10 produced by monocytes. J Exp Med,1991; 174(5):1 209.
[88]De Wall Malefyt R, Yssel H, Roncarolo M G, et al. Interleukin-10. Curr Opin Immunol,1992; 4(3):314.
[89]魏洪杰,肖文良,王士昌.因子白介素10和转化生长因子β与冠心病的关系[J].中华中西医杂志,2003；4(16)：2452-2456.
[90]Fiorentino D F, Zlotnik A, Vieira P, et al. IL-10 acts on the antigen presenting cell to inhibit cytokine production by Thl cells. J Immunol, 1991;146(10):3 444.
[91]De wall Malefyt R, Haanen J, Spits H, et al. Inter-luckin 10 and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class Ⅱ major histocompatibility complex expression. J Exp med,1991;174(4):915.
[92]Moore K W, Vieira P, Fiorentino D F, et al. Homol-ogy of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science, 1990; 248(4960):1230.
[93]OGarra A, Stapleton G, Dhar V, et al. Production of cytokines by mouse B cells:B lymphomas and normal B cells produce interleukin 10. Int Immunol, 1990; 2(9):821.
[94]Pinsky MR, Vincent JL, Deviere J, et al. Serum cytokine levels in human septic shock:relashion to multipie-system organ failure and mortality[J]. Chest,1993; 103:565-569.
[95]戴振英,李小攻,王海燕.白细胞介素-10对大鼠肾小球系膜细胞炎性效应的拮抗作用[J].中华医学杂志,1996；76(3)：407.
[96]Kitching AG, Tipping PG, Huang XR, et al. Interleukin-4 and interleukin-1 0 attenuate established crescentic glomerulonephritis in mice. Kidney lnt,1997; 52:52.
[97]Niemir ZI, Ondracek M, Dworacki G, et al. In situ upregulation of 1L-10 reflects the activity of human glomerulonephritis. Am J Kid Dis.1998; 32:40.
[98]王沙燕,戴勇,黄瑞芳,等.慢性肾衰患者血浆IL-10、IL-6、TNF-α量的变化及血液透析对其影响[J].上海免疫学杂志,2000；20(1)：55.
[99]Berre LL, Herve C, Buzelin F, et al. Renal macrophage activation and Th2 polarization precedes the development of nephrotic syndrome in Buffalo /Mna rats [J]. Kidney Int,2005; 68 (5):2079-2090.
[100]Malefyt RW, Figdor CG, Hui jbens R, et al. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes [J]. J Immunol,1993; 151(11):6370-6381.
[101]Punnonen J, Aversa G, Cooks BG, et al. Interlenkin 13 omdices interleukin 13 induces interleukin 4- independent IgG 4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci USA,1993; 90(8): 3730-3734.
[102]Defrance T, Carayon B, Billian G, et al. Interleukin 13 is a B cell stimulating factor. J Exp Med,1994; 179(1):135-143.
[103]Tan J, Delevran B, Gesser B, et al. Regulation of human T lymphocyte chemotaxis in vitro by T cell-derived cytokines IL-2, IFN-gamma, IL-4, IL-10, and IL-13, J Immunol,1995; 154(8):3742-3752.
[104]刘海燕,陈孝文,江黎明,等.原发性肾小球肾炎患者肾组织白细胞介素13表达及其作用[J].中国现代医学杂志,2003；13(1)：1-4.
[105]郭汉城,江黎明,陈孝文,等.白细胞介素13抑制肾小球系膜细胞增殖及白细胞介素6表达[J].中国病理生理杂志,2002；18(1)：76-79.
[106]王碧飞,江黎明,陈孝文,等.白细胞介素-13对肾小球系膜细胞炎症反应的拮抗作用[J].中国病理生理杂志,2004；20(3)：375-378.
[107]申燕,尹爱萍,冯学亮.白细胞介素13在肾小球疾病患者血清中的浓度及其意义[J].中国病理生理杂志,2004；24(11)：2120-2121,2133.
[108]张肇,陈孝文,江黎明,等.原发性肾病综合征患者IL-13血浆水平和基因表达的研究[J].肾脏病与透析肾移植杂志.1999；8(6)：539.
[109]Muzio M, Re F, Sironi M, et al. Interleukin-13 ind-uces the production of interleukin-1 receptor antagonist and the expression of the mRNA for the intracellular form of IL-lra in human myelomonocytic cells. Blood,1994; 83 (7):1 738.
[110]Minty A, chalon P, Derocq J M, et al. Interleukin 13 is a new human lymphokine regulating inflammatory and immune responses. Nature,1993; 362(6 417):248.
[111]Mckenzie A N J, Culpepper J A, de Wall Melefyt R, et al. INTERLEUKIN 13, a T cell derived cytokine that regulates human monocyte and B cell function. Proc Natl Acad Sci USA,1993; 90(8):3 735.
[112]Zurawski G, De Vries J E. Interleuckin 13, an inter-leukin 4 pike cytokine
that acts on monocytes and B cells, but not on T cells. Immunol Today, 1994; 15(1):19.
[113]陈爱华,陈荣华,吴元俊.原发性肾病综合征患儿外周血单个核细胞IL-13的表达及意义[J].中华儿科杂志,2000；38(3)：174-176.
[114]王先光,王兆全,李颖.黄蜀葵花的化学成分研究[J].植物学报,1981；23(3)：222-226.
[115]秦林,李楠.黄葵胶囊治疗慢性肾脏病临床应用述评[J].中国中西医结合肾病杂志,2009；10(7)：654-655.
[116]李就鸿,常巨平,林文胜.黄葵胶囊配合泼尼松治疗原发性肾病综合征疗效分析[J].中国药师,2004；7(12)：955-956.
[117]王锐艳,李吉河,崔岩.黄葵胶囊治疗原发性肾病综合征的临床观察[J].黑龙江医药科学,2007；30(2)：29-30.
[118]Du clos TW. Function of c-reactive protein, ANN Med,2000,32:274-278.
[119]Volanakis JE. Human c-reactive protein:expression, structure, and function. Mol Immunol,2001; 38:189-197.
[120]朱学云,钱卫东.高脂血症中医药研究进展[J].江苏中医,1998；19(6)：46-471.
[121]谢桂权.中医药治疗慢性肾炎蛋白尿七法[J].新中医,1986；19(2)：28-30.
[2]李志更,王天芳,赵燕,等.慢性肾功能衰竭常见证候与证候要素的现代文献分析比较[J].中华中医药学刊,2007；25(1)：52-53.
[3]孙伟,曾安平,严志林,等.湿热病邪与慢性肾病关系探讨：附152例临床资料分析[J].中医研究,2000；13(1)：36-37.
[4]沈庆法.中医肾脏病学[M].上海：上海中医药大学出版社,2008,53-54.
[5]周恩超.“肾实证”分类考辨[J].江苏中医药,2004；25(12)：5-6.
[6]陈以平,邓跃毅,张春菘.肾病的辨证与辨病治疗[M].北京：人民卫生出版社.2003,47.
[7]戴京璋.实用中医肾病学[M].北京：人民卫生出版社.2002,118.
[8]陈以平.湿热病邪与新月体肾炎[J].江苏中医药,2006；27(6)：3-4.
[9]时振声.时氏中医肾脏病学[M].北京：中国医药科技出版社,1997,1.
[10]沈庆法.肾病湿热证的研究[J].浙江中医学院学报,2000；24(1)：39.
[11]柳丛,饶向荣,李秀英,等.78例慢性肾脏病患者血瘀证与肾小管-间质病理损伤的相关性分析[J].中国中西医结合肾病杂志,2008；9(3)：251-253.
[12]李志更,王天芳,赵燕,等.慢性肾功能衰竭常见证候与证候要素的现代文献分析比较[J].中华中医药学刊,2007；25(1)：52-53.
[13]李晓政,闫彩香.代谢综合征及2型糖尿病慢性肾损害湿热血瘀证的相关研究[J].中国中医药科技,2007；14(6)：385-386.
[14]熊玮,王小琴,郭向东,等.慢性肾炎中医证候分布规律研究[J].临床肾脏病杂志,2008；8(3)：131-133.
[15]严志林,孙伟,等.湿热与原发性肾小球疾病关系的临床分析[J].湖北中医杂志,2005；27(10)：12-13.
[16]陈香美,陈以平,李平,等.1016例IgA肾病患者中医证候的多中心流行病学调查及相关因素分析[J].中国中西医结合杂志,2006；(26)3：197-201.
[17]桂泽红,马俊杰,邹川,等.50例肾移植受者中医证候特点分析[J].辽宁中医杂志2007；34(12)：1676-1677.
[18]邵光新,王亿平,曹恩泽,等.500例慢性肾功能衰竭中医证候特点分析[J].中华实用中西医杂志,2007；20(1)：994-995.
[19]阳晓,朱文锋,周小舟,等.慢性肾衰患者不同阶段病机证候特点临床分析[J]·中医杂志,2000；41(6)：350-352.
[20]余江毅,熊宁宁,余承惠.慢性肾病瘀血与湿热病理的临床和实验研究[J].辽宁中医杂志,1995；22(2)：91-92.
[21]王丽萍,陈建,庄永泽.IgA肾病湿热证与临床病理的相关性研究[J].中华中医药学刊,2008；26(1)：178-180.
[22]熊国良,李顺民,易铁钢,等.尿检异常IgA肾病湿热证微观指标的研究[J].中国医师杂志,2007；9(11)：1534-1535.
[23]李玲.肾病湿热浅析[J].中国中医急症,2007；16(2)：184-185.
[24]阮诗玮,郑敏麟,王智,等.IgA肾病湿热证与肾穿刺活检病理组织关系的临床研究[J].中国中西医结合肾病杂志,2003；4(10)：583-584.
[25]朱辟疆,韦先进,江丽萍,等.慢性肾小球疾病尿细胞因子改变及其与中医证型的关系[J].现代中西医结合杂志,2005；14(1)：20-22.
[26]朱辟疆,周逊,赵华等.慢性肾功能衰竭微炎症状态与中医证型关系研究[J].现代中西医结合杂志,2008；17(5)：652-654.
[27]吴仕九,廖礼兵.湿热证大鼠肾内髓及尿液中水通道蛋白AQP2含量的变化[J].中国中医药科技,2003；10(1)：4-5.
[28]王亿平,茅燕萍,曹恩泽,等.清肾颗粒对慢性肾功能衰竭急剧加重湿热证患者肿瘤坏死因子及其受体的干预作用[J].中国中西医结合急救杂志,2006；13(3)：135-138.
[29]解汝娟,晋青,那士平.C-反应蛋白和肿瘤坏死因子与慢性肾功能衰竭[J].中国康复医学.2003；7：3023-3024.
[30]周莺,李俊彪,伍新林,等.丹芍汤对慢性原发性肾小球疾病尿IL-6水平的影响[J].中国中医药信息杂志,2003；10(1)：12-14.
[31]盛梅笑.孙伟.贾宁人,等.肾炎湿热证血清sICAM—1变化的临床观察[J],辽宁中医杂志,2003；30(11)：891-892.
[32]朱辟疆,施荣华,刘永平.慢性肾小球疾病湿热证血浆及尿白介素-6(IL-6)的改变[J].浙江中西医结合杂志,1999；9(2)：75.
[33]邸若虹,李永健,童瑶.湿热证“正盛邪实”病机浅探[J].中医药学刊,2004；22(1)：106-109.
[34]焦钦安.从湿热毒论治IrA肾病[J].福建中医药,2004；35(4)：55-56.
[35]张大宁,沈伟梁,张勉之,等.“肾虚血瘀·湿热论”与港、澳地区慢性肾炎发病关系的研究[J].中国中医基础医学杂志,2003；9(6)：401-403.
[36]张琪.张琪临床经验辑要[M].北京：中国医药科技出版社,1998,49-62.
[37]傅文录.时振声辨治肾病湿热证经验[J].中医研究,1995；8(3)：24.
[38]卢远航.以湿热论治肾病综合征191例[J].陕西中医,1998；19(10)：439-440.
[39]方小南.龙胆泻肝汤加减治疗难治性肾病综合征18例疗效观察[J].中国中医基 础医学杂志,2002；8(8)：60.
[40]刘建国.中西医结合治疗难治性肾病的良方妙法[M].北京：中国医药科技出版社,2000,138.
[41]黄国东,何小萍,向少伟,等.清热利湿活血法治疗隐匿型IgA肾病的临床观察[J].吉林中医药,2007；27(10)：11-14.
[42]何小萍.论清利湿热法是原发性肾小球疾病的重要治法[J].河南中医药学刊,2002；17(3)：77.
[43]刘宝厚,甘培尚,杨扬.肾复康1号颗粒治疗慢性肾小球肾炎临床疗效观察[J].中国中西医结合肾病杂志,2004；5(10)：583-584.
[44]吴立友,饶家珍,赖申昌.等.肾衰方治疗慢性肾衰竭湿热证的临床研[J].时珍国医国药,2007；18(1)：175-176.
[45]李聃丹,刘小菁,陶冶.肾病综合征患者血清sCD40L与血脂水平相关性研究[J].西部医学,2006；18(2)：137-138.
[46]张小妮,金敏.小儿肾病综合征与CuZn-SOD、GSH-Px及MDA的相关性研究[J].甘肃医药,2008；27(2)：10-12.
[47]李苗苗.血清FT3、FT4浓度变化与肾病综合征的关系[J].中国现代药物应用,2009；3(2)：106.
[48]付瑶,潘晓芳.不同程度尿蛋白患者血清甲状腺激素水平变化及其临床意义[J].医学与哲学(临床决策论坛),2009；30(1)：36-37.
[49]黄慧.肾病综合征患者血IL-8水平变化及其临床意义[J].常州实用医学,2008；24(5)：300-301.
[50]张洪亚,张平,高泉.肾病综合征患者血IL—8与尿IL—8水平测定的临床意义[J].淮海医药,2003；21(6)：444-445.
[51]常月琴,周成林.肾病综合征患者血和尿IL-8测定的临床意义[J],江苏大学学报(医学版),2006；16(3)：251-252.
[521李宇颖,刘素雁,刘晓刚.原发性肾病综合征患者血清IL-2、IL-13的研究[J].哈尔滨医科大学学报,2005；39(2)：190-193.
[53]胡昭,江蓓,郭齐,等.原发性肾病综合征患者治疗前后血及尿IL-8、IL-13水平测定及其临床意义[J].山东医科大学学报,2002；40(1)：70—71.
[54]邓颖敏.高岩肾病综合征患儿外周血单个核细胞核因子-KB活性水平观察[J].实用医学杂志,2006；22(1)：49-50.
[55]刘宏伟.肾病湿热证的实验研究进展[J].中国中医基础医学杂志[J].1995；1(4)：35.
[56]孙伟,曾安平,严志林,等.湿热病邪与慢性肾病关系探讨：附152例临床资料分析[J].中医研究2000；13(1)：36-37.
[57]侯安会,王磊.肾病湿热探讨[J].黑龙江中医药,2000；(1)：5.
[58]陈伊伦,张华滋,陈文清.肾病综合征感染并发症防治探讨[J].浙江医学,2007；29(4)：363-406.
[59]刘芸芳,彭小梅,唐盛.成人肾病综合征医院感染的临床分析[J].现代中西医结合杂志,2008；17(32)：5000-5001.
[60]文细毛,任南,徐秀华,等.全国医院感染监控网医院感染病原菌分布及耐药性分析[J].中华医院感染学杂志,2002；12(4)：241-224.
[61]张友道,叶任高,李幼姬.成人原发性肾病综合征临床及实验系列研究[J].医学研究通讯,2001；30(1)：18-19.
[62]刘刚,章友康,谌贻璞.肾病综合征的常见并发症[J].临床肾脏病杂志,2008；8(4)：183-184.
[63]沈庆法.肾脏病湿热证的研究(续)[J].浙江中医学院学报,2000；24(2)：15.
[64]谢桂权,高颖,冯天保,等.清热利湿法治疗肾病综合征湿热证45例疗效观察[J].新中医,2007；39(10)：85-87.
[65]伊娜.曹式丽治疗老年原发性肾病综合征感染并发症的经验[J].辽宁中医杂志,2008,36(8)：1135-1136.
[66]张淑君.益气养阴利湿热法治疗肾病综合征30例[J].实用中医内科杂志,2007；21(7)：62.
[67]李永伟,李棱彪,扬宏志,等.原发性肾病综合征(PNS)患者血清IL-6、IgG水平与中医分型的相关性[J].中国中医药信息杂志,2001；8(6)：47-48.
[68]聂莉芳.肾病湿热证辨治刍议[J].江苏中医药,2006；27(6)：9.
[69]安辉.肾病综合征难治因素的分析[J].湖北中医学院学报,2004；6(2)：42-44.
[70]Pinsky MR. Dysregulation of the immune response in severe sepsis. Am J Med Sci,2004; 328(4):220-229.
[71]刘江文.炎性细胞因子和外科感染[J].华西医学,2003,18(2)：274-275.
[72]赵有成,魏宏建,段勇.重症感染者血中IL26和TNF2α检测的意义[J].中国抗感染化疗杂志.2003；3(5)：315-317.
[73]Arend W P. Interleukin 1 receptor antagonist:A new member of the interleukin 1 family. J Clin Invest,1991; 88(5):1445.
[74]李君蕊,赵宝春,辛桂荣.抗炎因子与感染的关系研究进展[J].中国煤炭工业医学杂志,2008；11(2)：268-270.
[75]Hart P H, Vitti G F, Burgess D R, et al. Potential antiinflammatory effects of interleukin 4:suppression of human monocyte tumor necrosis factor alpha, interleukin 1 and prostaglandin E2. Natl Acad Sci USA,1989; 86(10):3 803.
[76]Te Velde A A, Hui jbens R J F, Hei je K, et al. Inter-leukin-4 inhibits secretion of IL-1β, tumor necrosis factor a and IL-6 by human monocytes. Blood,1990; 76(7):1392. Standiford T J, Strieter R M, Chensue S W, et al. IL-4 inhibits the expression of IL-8 from stimulated human monocytes. J Immunol,1990; 145(5):1 435.
[77]Al-Ramadi B K, Meissler J J, Huang D, et al. Imm-unosuppression induced by nitric oxide and its inhibition by interleukin-4. Eur J Immunol,1992; 22(9):2 249.
[78]Jenkins J K, Arend W P. Interleukin 1 receptor anta-gonist production in human monocytes is induced by IL-1 αlpha, IL-13, IL-4 and GM-CSF. Cytokine,1993; 5(5):407.
[79]Corcoran M L, stetler-Stevenson W G, Brown P D, et al. Interleukin 4 inhibition of prostaglandin E2 synthesis blocks interstitial collagenase and 92-KDa type IV collagenase/gelatinase production by human monocytes. J Biol Chem,1992; 267(1):515.
[80]Hiester A A, Metcalf D R, Campbell P A. Interleu-kin-4 is chemotactic for mouse macrophages. Cell Immunol,1992; 139(1):72.
[81]Beckmann M P, Cosman D, Fanslow W, et al. The interleukin-4 receptor: structure, function, and signal transduction. Chem Immunol,1992; 51(1):107.
[82]Gharee-Kermani M. Phan SH. Role of eytokines and eytokine therapy in wound healing and fibrotic disease Curr Pharm Des,2001; 7,1083-1087.
[83]齐文杰,任爱民,张淑文,等.血清促炎因子、抗炎因子在急性感染患者中的动态变化及中药干预的影响[J].中国中西医结合杂志,2000；20(11)：824—827.
[84]Majori M, Caminati A. Predominant TH1 cytokine pattern in peripheral blood from subjects with chronic obstructive pulmonary disease[J]. J Allergy ClinImmunol,1999; 103(3 pt 1):458-462.
[85]周道远,李幼姬,王俭勤,等.干扰素-γ和白细胞介素4对狼疮肾炎患者巨噬细胞炎症蛋白-1α产生的效应[J].中华肾脏病杂志,2002；18(1)：25-28.
[86]Del Prete G, De Carli M, Almerigogno F, et al. Human IL-10 is produced by both type 1 helper (Thl) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol,1993;150(2):353.
[87]De Wall Malefyt R, Abrams J, Bennett B, et al. Interleukin 10(IL-10)inhibits cytokine synthesis by human monocytes:An autoregulatory role of IL-10 produced by monocytes. J Exp Med,1991; 174(5):1 209.
[88]De Wall Malefyt R, Yssel H, Roncarolo M G, et al. Interleukin-10. Curr Opin Immunol,1992; 4(3):314.
[89]魏洪杰,肖文良,王士昌.因子白介素10和转化生长因子β与冠心病的关系[J].中华中西医杂志,2003；4(16)：2452-2456.
[90]Fiorentino D F, Zlotnik A, Vieira P, et al. IL-10 acts on the antigen presenting cell to inhibit cytokine production by Thl cells. J Immunol, 1991;146(10):3 444.
[91]De wall Malefyt R, Haanen J, Spits H, et al. Inter-luckin 10 and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class Ⅱ major histocompatibility complex expression. J Exp med,1991;174(4):915.
[92]Moore K W, Vieira P, Fiorentino D F, et al. Homol-ogy of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science, 1990; 248(4960):1230.
[93]OGarra A, Stapleton G, Dhar V, et al. Production of cytokines by mouse B cells:B lymphomas and normal B cells produce interleukin 10. Int Immunol, 1990; 2(9):821.
[94]Pinsky MR, Vincent JL, Deviere J, et al. Serum cytokine levels in human septic shock:relashion to multipie-system organ failure and mortality[J]. Chest,1993; 103:565-569.
[95]戴振英,李小攻,王海燕.白细胞介素-10对大鼠肾小球系膜细胞炎性效应的拮抗作用[J].中华医学杂志,1996；76(3)：407.
[96]Kitching AG, Tipping PG, Huang XR, et al. Interleukin-4 and interleukin-1 0 attenuate established crescentic glomerulonephritis in mice. Kidney lnt,1997; 52:52.
[97]Niemir ZI, Ondracek M, Dworacki G, et al. In situ upregulation of 1L-10 reflects the activity of human glomerulonephritis. Am J Kid Dis.1998; 32:40.
[98]王沙燕,戴勇,黄瑞芳,等.慢性肾衰患者血浆IL-10、IL-6、TNF-α量的变化及血液透析对其影响[J].上海免疫学杂志,2000；20(1)：55.
[99]Berre LL, Herve C, Buzelin F, et al. Renal macrophage activation and Th2 polarization precedes the development of nephrotic syndrome in Buffalo /Mna rats [J]. Kidney Int,2005; 68 (5):2079-2090.
[100]Malefyt RW, Figdor CG, Hui jbens R, et al. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes [J]. J Immunol,1993; 151(11):6370-6381.
[101]Punnonen J, Aversa G, Cooks BG, et al. Interlenkin 13 omdices interleukin 13 induces interleukin 4- independent IgG 4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci USA,1993; 90(8): 3730-3734.
[102]Defrance T, Carayon B, Billian G, et al. Interleukin 13 is a B cell stimulating factor. J Exp Med,1994; 179(1):135-143.
[103]Tan J, Delevran B, Gesser B, et al. Regulation of human T lymphocyte chemotaxis in vitro by T cell-derived cytokines IL-2, IFN-gamma, IL-4, IL-10, and IL-13, J Immunol,1995; 154(8):3742-3752.
[104]刘海燕,陈孝文,江黎明,等.原发性肾小球肾炎患者肾组织白细胞介素13表达及其作用[J].中国现代医学杂志,2003；13(1)：1-4.
[105]郭汉城,江黎明,陈孝文,等.白细胞介素13抑制肾小球系膜细胞增殖及白细胞介素6表达[J].中国病理生理杂志,2002；18(1)：76-79.
[106]王碧飞,江黎明,陈孝文,等.白细胞介素-13对肾小球系膜细胞炎症反应的拮抗作用[J].中国病理生理杂志,2004；20(3)：375-378.
[107]申燕,尹爱萍,冯学亮.白细胞介素13在肾小球疾病患者血清中的浓度及其意义[J].中国病理生理杂志,2004；24(11)：2120-2121,2133.
[108]张肇,陈孝文,江黎明,等.原发性肾病综合征患者IL-13血浆水平和基因表达的研究[J].肾脏病与透析肾移植杂志.1999；8(6)：539.
[109]Muzio M, Re F, Sironi M, et al. Interleukin-13 ind-uces the production of interleukin-1 receptor antagonist and the expression of the mRNA for the intracellular form of IL-lra in human myelomonocytic cells. Blood,1994; 83 (7):1 738.
[110]Minty A, chalon P, Derocq J M, et al. Interleukin 13 is a new human lymphokine regulating inflammatory and immune responses. Nature,1993; 362(6 417):248.
[111]Mckenzie A N J, Culpepper J A, de Wall Melefyt R, et al. INTERLEUKIN 13, a T cell derived cytokine that regulates human monocyte and B cell function. Proc Natl Acad Sci USA,1993; 90(8):3 735.
[112]Zurawski G, De Vries J E. Interleuckin 13, an inter-leukin 4 pike cytokine
that acts on monocytes and B cells, but not on T cells. Immunol Today, 1994; 15(1):19.
[113]陈爱华,陈荣华,吴元俊.原发性肾病综合征患儿外周血单个核细胞IL-13的表达及意义[J].中华儿科杂志,2000；38(3)：174-176.
[114]王先光,王兆全,李颖.黄蜀葵花的化学成分研究[J].植物学报,1981；23(3)：222-226.
[115]秦林,李楠.黄葵胶囊治疗慢性肾脏病临床应用述评[J].中国中西医结合肾病杂志,2009；10(7)：654-655.
[116]李就鸿,常巨平,林文胜.黄葵胶囊配合泼尼松治疗原发性肾病综合征疗效分析[J].中国药师,2004；7(12)：955-956.
[117]王锐艳,李吉河,崔岩.黄葵胶囊治疗原发性肾病综合征的临床观察[J].黑龙江医药科学,2007；30(2)：29-30.
[118]Du clos TW. Function of c-reactive protein, ANN Med,2000,32:274-278.
[119]Volanakis JE. Human c-reactive protein:expression, structure, and function. Mol Immunol,2001; 38:189-197.
[120]朱学云,钱卫东.高脂血症中医药研究进展[J].江苏中医,1998；19(6)：46-471.
[121]谢桂权.中医药治疗慢性肾炎蛋白尿七法[J].新中医,1986；19(2)：28-30.