糖尿病证候—基因组及其双生子的追踪研究
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摘要
目的：
1.证候：研究糖尿病肾虚证等基本证候及其主要症状在糖尿病中的分布规律,为辨证论治提供新的依据。
2.基因：集约于双生子筛选糖尿病肾虚证的候选基因并对其验证,促进证候-基因组研究的深入发展。
方法：
1.长期观察法：采用病证结合方法连续5年追踪观察一对糖尿病双生子证候。
2.医案计量法：将古代消渴医案与当今糖尿病医案进行半定量的分析研究。
3.临床调查法：用四诊、肾虚、血瘀等中医临床量表进行糖尿病临床调查。
4.实验验证法：采用以基因芯片为代表的转录组技术,对糖尿病肾虚证双生子系统地筛选差异表达基因谱,并采用实时定量PCR进行验证。
结果：
1.五年来系统地观察了糖尿病双生子主要证候的发生发展的动态变化。
2.比较古今医案中,糖尿病肾虚证在三多一少等主要症状的诊治方面的异同。
3.糖尿病肾虚证中,肾阳虚、肾阴虚、肾精虚、肾气虚四个证型的分布规律。
4.基于糖尿病家系背景,发现北方糖尿病的证候重于南方,并可视性地表述。
5.白介素-18等免疫类基因作为糖尿病肾虚证的候选基因得到初步验证。
结论：
“动态时空”,从纵向空间而论,从数百对双生子中精选一对单卵双生子,对宏观的证候与微观的基因进行了连续5年的长期观察,以转录组为中心的技术支撑,筛选出糖尿病肾虚证的候选基因组,为证候-基因组的深入研究提供了一个范例。
“多维界面”,从横向空间而论,以糖尿病肾虚证候为中心,展开了肾虚证与血瘀证,家系遗传背景的有与无,进行了多资源、多方法的证候研究,对正确进行糖尿病的辨证论治有着积极意义。
Objective:
1. To explore clinical index for kidney-deficiency syndrome in type 2 diabetes.
2. To explore candidate genes and their molecular mechanisms of kidney-deficiency diabetes through typical twins research.
Method:
1. Five-year consecutive observations for a monozygotic twin pair with kidney-deficiency diabetes.
2. Statistical analysis for historical and current survey medical data.
3. Clinical investigations with scaling tables on four diagnosis, kidney-deficiency, and blood stasis.
4. cDNA microarray tests to screen out potential differentially expressed genes for type 2 diabetes and real-time PCR tests for the verification of these genes.
Results:
1. A twin pair and her families were systematically investigated for the evolution of their kidney-deficiency diabetes during the last consecutive five year periods.
2. The similarities and differences of behaviors between modern and ancient diabetes were identified.
3. The distribution of kidney-deficiency diabetes was explored through syndrome sub-classes of kidney-yang deficiency, kidney-yin deficiency, kidney-jin deficiency, and kidney-qi deficiency.
4. It was discovered that the symptoms of diabetes were heavier in North China than in South China.
5. Gene interleukin-18 was screened out and verified as a candidate gene which may play important roles in kidney-deficiency diabetes.
Discussion:
Based on my Master Thesis of'Kidney-deficiency syndrome and gene expression profile
of a twin pair of diabetics', this dissertation is further extended in two fields:
First, multi-disciplines, multi-resources and multi-approaches were comprehensively employed to explore the distribution of kidney-deficiency diabetes. The relationship between syndrome in TCM and differentially expressed genes was further explored.
Second, some candidate genes were screened out and verified through five-year consecutive observations on a monozygotic twin pair with kidney-deficiency diabetes.
1.证候：研究糖尿病肾虚证等基本证候及其主要症状在糖尿病中的分布规律,为辨证论治提供新的依据。
2.基因：集约于双生子筛选糖尿病肾虚证的候选基因并对其验证,促进证候-基因组研究的深入发展。
方法：
1.长期观察法：采用病证结合方法连续5年追踪观察一对糖尿病双生子证候。
2.医案计量法：将古代消渴医案与当今糖尿病医案进行半定量的分析研究。
3.临床调查法：用四诊、肾虚、血瘀等中医临床量表进行糖尿病临床调查。
4.实验验证法：采用以基因芯片为代表的转录组技术,对糖尿病肾虚证双生子系统地筛选差异表达基因谱,并采用实时定量PCR进行验证。
结果：
1.五年来系统地观察了糖尿病双生子主要证候的发生发展的动态变化。
2.比较古今医案中,糖尿病肾虚证在三多一少等主要症状的诊治方面的异同。
3.糖尿病肾虚证中,肾阳虚、肾阴虚、肾精虚、肾气虚四个证型的分布规律。
4.基于糖尿病家系背景,发现北方糖尿病的证候重于南方,并可视性地表述。
5.白介素-18等免疫类基因作为糖尿病肾虚证的候选基因得到初步验证。
结论：
“动态时空”,从纵向空间而论,从数百对双生子中精选一对单卵双生子,对宏观的证候与微观的基因进行了连续5年的长期观察,以转录组为中心的技术支撑,筛选出糖尿病肾虚证的候选基因组,为证候-基因组的深入研究提供了一个范例。
“多维界面”,从横向空间而论,以糖尿病肾虚证候为中心,展开了肾虚证与血瘀证,家系遗传背景的有与无,进行了多资源、多方法的证候研究,对正确进行糖尿病的辨证论治有着积极意义。
Objective:
1. To explore clinical index for kidney-deficiency syndrome in type 2 diabetes.
2. To explore candidate genes and their molecular mechanisms of kidney-deficiency diabetes through typical twins research.
Method:
1. Five-year consecutive observations for a monozygotic twin pair with kidney-deficiency diabetes.
2. Statistical analysis for historical and current survey medical data.
3. Clinical investigations with scaling tables on four diagnosis, kidney-deficiency, and blood stasis.
4. cDNA microarray tests to screen out potential differentially expressed genes for type 2 diabetes and real-time PCR tests for the verification of these genes.
Results:
1. A twin pair and her families were systematically investigated for the evolution of their kidney-deficiency diabetes during the last consecutive five year periods.
2. The similarities and differences of behaviors between modern and ancient diabetes were identified.
3. The distribution of kidney-deficiency diabetes was explored through syndrome sub-classes of kidney-yang deficiency, kidney-yin deficiency, kidney-jin deficiency, and kidney-qi deficiency.
4. It was discovered that the symptoms of diabetes were heavier in North China than in South China.
5. Gene interleukin-18 was screened out and verified as a candidate gene which may play important roles in kidney-deficiency diabetes.
Discussion:
Based on my Master Thesis of'Kidney-deficiency syndrome and gene expression profile
of a twin pair of diabetics', this dissertation is further extended in two fields:
First, multi-disciplines, multi-resources and multi-approaches were comprehensively employed to explore the distribution of kidney-deficiency diabetes. The relationship between syndrome in TCM and differentially expressed genes was further explored.
Second, some candidate genes were screened out and verified through five-year consecutive observations on a monozygotic twin pair with kidney-deficiency diabetes.
引文
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