糖尿病肾病证候演变及其中医药干预研究
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摘要
目的：研究早期糖尿病肾病(diabetic nephropathy, DN)和临床DN证候演变特点,以及不同干预对糖尿病肾病证候的影响,为揭示糖尿病肾病中医证候演变规律奠定基础。
方法：本课题依托国家“十一五”科技支撑计划中医药全程干预糖尿病肾病进程综合方案研究,病例来源自北京中医药大学东直门医院等10家参研单位,按照统一制定的调查表对早期DN和临床DN患者的一般情况、中医信息、中西医干预后3个时点的中医四诊信息进行收集、录入数据库、审核无误后提交锁定。
研究一：对第0时点早期DN和临床期D N主要症状分布、常见证素分布进行横断面研究,包括描述、频数统计和构成比统计,对证素组合应用数据库进行聚合分析。
研究二：对中药和西药干预后早期DN和临床期DN 4个时点的证素变化趋势、药物干预作用及药物和分期的交互作用应用重复测量方差分析进行分析。
研究三：对早期DN和临床期DN的疾病病性演变应用转移概率进行研究。对患者0时点、1时点、2时点的证候应用因子分析进行分类,应用转移概率矩阵对0时点、1时点、2时点的证候演变进行分析。
结果：
研究一：随着DN病情由早期进展到临床期,出现频率有明显变化的症状有面足浮肿、怕热盗汗、畏寒肢冷、腰膝怕冷、夜尿频多等。临床期DN与早期DN相比，面足浮肿症状增多(X2=19.474,P=0.000),具有显著性差异。怕热盗汗症状减少(X2=5.740,P=0.017)具有显著性差异。畏寒肢冷症状增多(X2=4.098,P=0.043)具有显著性差异。在证素方面,临床期DN阳虚证素较早期DN阳虚证素增多(X2=11.579,P=0.001)临床期湿浊证素较早期湿浊证素增多(X2=13.478,P=0.000),血瘀证素贯穿早期和临床期是出现最多的邪实证素。
研究二：对中西医干预后糖尿病肾病证素变化趋势进行分析,随着时间的变化中药组和厄贝沙坦组的证素都有下降趋势,且具有显著性差异,中药组方和厄贝沙坦对糖尿病肾病证素都有改善作用。中药组方对早期DN气虚证素的疗效好于厄贝沙坦,对其他证素的改善,中药组方和西药没有显著性差异,中药组方对证素的改善有优于西药组的趋势。
研究三：对DN证候特点进行转移概率分析,早期DN和临床期DN证候特点都是以虚实夹杂证为主,在4个时点的转化过程中虚实夹杂继续保持虚实夹杂的比例都非常高,即虚实夹杂证素是糖尿病肾病的主要证候特点。单纯的虚证和单纯实证比例较小,且不稳定,容易转化为其他病性。
根据症状DN病例症状的内在联系,应用因子分析对每个时点的证候进行分组,第0时点分为8组,第1时点分为10组,第2时点分为9组。将3个时点的证候进行演变规律研究,结果认为各证候都有保持原有状态的稳定性,总体证候变化多样,证候转化有一定特点,其中包括：阳虚有向阳虚痰湿转化的趋势,阴虚有向气虚阴虚阳虚转化的趋势,气虚痰湿有向气虚痰湿湿浊转化的趋势,血瘀证具有相对的稳定性。
结论：从症状、证素和证候的分布演变研究中得到较为一致的结论
1.随着病DN情由早期演变到临床期,体现阴虚内热伤阴病机的症状逐渐减少,体现阳虚的症状、证素呈现逐渐增多的趋势,临床期DN湿浊证素较早期DN逐渐增多。反映糖尿病肾病病机从早期到临床期呈现气阴两虚发展向阴阳两虚的趋势,邪实的证候贯穿早期和临床期,并有增多的趋势,其中临床期DN湿浊证素较早期DN明显增加。
2.中药组方和厄贝沙坦都能改善糖尿病肾病证素,在接受干预后,两组各证素具有改善趋势,但具有波动性。考虑原因在于临床疾病与证候具有统一性,在临床治疗中只要切中发病机制,符合中医病机都会取得疗效。
3.糖尿病肾病的证候特点是虚实夹杂,DN病机具有阶段性,同一临床阶段具有共同的病机特点,证候演变具有稳定性,同时又复杂多样,提示DN分期辨证论治的思路可行。
Objective
To discuss the Evolution of TCM syndrome of diabetic nephropathyⅢandⅣand the influence to the syndrome by either Chinese herbs and Irbesartan aiming to lay a foundation for the Evolution of TCM syndrome in this flied.
Methods
The research had been carried out with a RCT, collecting the Diabetic Nephropathy sufferer came from Dozhimen Hospital of Peking Chinese Medicine University and 9 other hospitals.General informations, four diagnostic methods information from the starting point wre collected and the other 3 times of four diagnostic methods information of TCM while the patients got treatment were also collected, totally information of 4 times of one year. The data was kept by a database after confirmation
Clinical Sydrome Study 1:Descriptive and chi-square were adopted for the distributing of TCM syndrome; while accumulation analysis for syndrome elements.
Clinical Sydrome Study 2:Repeated measures GLM were used to analyze the changing of the syndrome elements marks,the effection of the Irbesartan and the herbs and also the interaction of the grouping and DN stage.
Clinical Sydrome Study 3:Factor analysis was used for categoryg the patients according to different syndromes. Transition probability matrix was used to analyze the evolution of the syndrome and the evolution of the nature of the disease.
Results
We discovered that there are different symptom, syndrome, syndrome elements of highest frequency for either stage of DN.There was difference of yang deficiency (X2=11.579 P=0.001) and dampness turbid (X2= 13.478 P=0. 000) between the two stages,Compared with phlegm dampness and dampness turbid, blood stasis were more frequent and it appeared early in DN.
TCM group and the WM group got significant changing in the 7 syndrome elements. For most of the syndrome elements there were no differents between the changing, but for qi deficiency syndrome element TCM group got a better result comepared with the WM group.
The result of the disease nature study showed that most common disease nature is deficiency and excess,which was also stable.Neither pure deficiency and pure excess got much frequency，nor was the stability.
Patients had been categoryied into 8 gourps for point 0,10 groups for point 1 and 9 groups for point 2. Some of the original syndrome last till next point, there were varieties of changes of the syndrome,there were still some paths:yang deficiency turned out to be yang deficiency and dampness and phlem,yin deficiency,turned out to be yin qi yang deficiency.qi deficiency and phlem and dampness turned out to be qi deficiency and phlem and dampness and dampness turbid
Conclusion
1.There were differences between the of the two stages.As a process the Pathogenesis was beginning as "inner heat hurt qi "towards "yinyang deficiency". Yang deficiency was gradually apparent during the course. Phlegm dampness and dampness turbid were key pathological factors "
2.The results of GLM analysis showed that syhdrome elements marks had all decreased through the period significantly,TCM got a better result in qixu syhdrome element while the results of the other syhdrome elements were close.So the idea of disease and syndrome unifying wre highlighted.
3. The nature of DN was deficiency and excess, the pathogenesis could be stages.The same stage seemed to have the same pathogenesis, the changes of the syndrone were various,as a result stage differentiation syndrome was recommend.
方法：本课题依托国家“十一五”科技支撑计划中医药全程干预糖尿病肾病进程综合方案研究,病例来源自北京中医药大学东直门医院等10家参研单位,按照统一制定的调查表对早期DN和临床DN患者的一般情况、中医信息、中西医干预后3个时点的中医四诊信息进行收集、录入数据库、审核无误后提交锁定。
研究一：对第0时点早期DN和临床期D N主要症状分布、常见证素分布进行横断面研究,包括描述、频数统计和构成比统计,对证素组合应用数据库进行聚合分析。
研究二：对中药和西药干预后早期DN和临床期DN 4个时点的证素变化趋势、药物干预作用及药物和分期的交互作用应用重复测量方差分析进行分析。
研究三：对早期DN和临床期DN的疾病病性演变应用转移概率进行研究。对患者0时点、1时点、2时点的证候应用因子分析进行分类,应用转移概率矩阵对0时点、1时点、2时点的证候演变进行分析。
结果：
研究一：随着DN病情由早期进展到临床期,出现频率有明显变化的症状有面足浮肿、怕热盗汗、畏寒肢冷、腰膝怕冷、夜尿频多等。临床期DN与早期DN相比，面足浮肿症状增多(X2=19.474,P=0.000),具有显著性差异。怕热盗汗症状减少(X2=5.740,P=0.017)具有显著性差异。畏寒肢冷症状增多(X2=4.098,P=0.043)具有显著性差异。在证素方面,临床期DN阳虚证素较早期DN阳虚证素增多(X2=11.579,P=0.001)临床期湿浊证素较早期湿浊证素增多(X2=13.478,P=0.000),血瘀证素贯穿早期和临床期是出现最多的邪实证素。
研究二：对中西医干预后糖尿病肾病证素变化趋势进行分析,随着时间的变化中药组和厄贝沙坦组的证素都有下降趋势,且具有显著性差异,中药组方和厄贝沙坦对糖尿病肾病证素都有改善作用。中药组方对早期DN气虚证素的疗效好于厄贝沙坦,对其他证素的改善,中药组方和西药没有显著性差异,中药组方对证素的改善有优于西药组的趋势。
研究三：对DN证候特点进行转移概率分析,早期DN和临床期DN证候特点都是以虚实夹杂证为主,在4个时点的转化过程中虚实夹杂继续保持虚实夹杂的比例都非常高,即虚实夹杂证素是糖尿病肾病的主要证候特点。单纯的虚证和单纯实证比例较小,且不稳定,容易转化为其他病性。
根据症状DN病例症状的内在联系,应用因子分析对每个时点的证候进行分组,第0时点分为8组,第1时点分为10组,第2时点分为9组。将3个时点的证候进行演变规律研究,结果认为各证候都有保持原有状态的稳定性,总体证候变化多样,证候转化有一定特点,其中包括：阳虚有向阳虚痰湿转化的趋势,阴虚有向气虚阴虚阳虚转化的趋势,气虚痰湿有向气虚痰湿湿浊转化的趋势,血瘀证具有相对的稳定性。
结论：从症状、证素和证候的分布演变研究中得到较为一致的结论
1.随着病DN情由早期演变到临床期,体现阴虚内热伤阴病机的症状逐渐减少,体现阳虚的症状、证素呈现逐渐增多的趋势,临床期DN湿浊证素较早期DN逐渐增多。反映糖尿病肾病病机从早期到临床期呈现气阴两虚发展向阴阳两虚的趋势,邪实的证候贯穿早期和临床期,并有增多的趋势,其中临床期DN湿浊证素较早期DN明显增加。
2.中药组方和厄贝沙坦都能改善糖尿病肾病证素,在接受干预后,两组各证素具有改善趋势,但具有波动性。考虑原因在于临床疾病与证候具有统一性,在临床治疗中只要切中发病机制,符合中医病机都会取得疗效。
3.糖尿病肾病的证候特点是虚实夹杂,DN病机具有阶段性,同一临床阶段具有共同的病机特点,证候演变具有稳定性,同时又复杂多样,提示DN分期辨证论治的思路可行。
Objective
To discuss the Evolution of TCM syndrome of diabetic nephropathyⅢandⅣand the influence to the syndrome by either Chinese herbs and Irbesartan aiming to lay a foundation for the Evolution of TCM syndrome in this flied.
Methods
The research had been carried out with a RCT, collecting the Diabetic Nephropathy sufferer came from Dozhimen Hospital of Peking Chinese Medicine University and 9 other hospitals.General informations, four diagnostic methods information from the starting point wre collected and the other 3 times of four diagnostic methods information of TCM while the patients got treatment were also collected, totally information of 4 times of one year. The data was kept by a database after confirmation
Clinical Sydrome Study 1:Descriptive and chi-square were adopted for the distributing of TCM syndrome; while accumulation analysis for syndrome elements.
Clinical Sydrome Study 2:Repeated measures GLM were used to analyze the changing of the syndrome elements marks,the effection of the Irbesartan and the herbs and also the interaction of the grouping and DN stage.
Clinical Sydrome Study 3:Factor analysis was used for categoryg the patients according to different syndromes. Transition probability matrix was used to analyze the evolution of the syndrome and the evolution of the nature of the disease.
Results
We discovered that there are different symptom, syndrome, syndrome elements of highest frequency for either stage of DN.There was difference of yang deficiency (X2=11.579 P=0.001) and dampness turbid (X2= 13.478 P=0. 000) between the two stages,Compared with phlegm dampness and dampness turbid, blood stasis were more frequent and it appeared early in DN.
TCM group and the WM group got significant changing in the 7 syndrome elements. For most of the syndrome elements there were no differents between the changing, but for qi deficiency syndrome element TCM group got a better result comepared with the WM group.
The result of the disease nature study showed that most common disease nature is deficiency and excess,which was also stable.Neither pure deficiency and pure excess got much frequency，nor was the stability.
Patients had been categoryied into 8 gourps for point 0,10 groups for point 1 and 9 groups for point 2. Some of the original syndrome last till next point, there were varieties of changes of the syndrome,there were still some paths:yang deficiency turned out to be yang deficiency and dampness and phlem,yin deficiency,turned out to be yin qi yang deficiency.qi deficiency and phlem and dampness turned out to be qi deficiency and phlem and dampness and dampness turbid
Conclusion
1.There were differences between the of the two stages.As a process the Pathogenesis was beginning as "inner heat hurt qi "towards "yinyang deficiency". Yang deficiency was gradually apparent during the course. Phlegm dampness and dampness turbid were key pathological factors "
2.The results of GLM analysis showed that syhdrome elements marks had all decreased through the period significantly,TCM got a better result in qixu syhdrome element while the results of the other syhdrome elements were close.So the idea of disease and syndrome unifying wre highlighted.
3. The nature of DN was deficiency and excess, the pathogenesis could be stages.The same stage seemed to have the same pathogenesis, the changes of the syndrone were various,as a result stage differentiation syndrome was recommend.
引文
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