ACE和eNOS单核苷酸多态性与系统性红斑狼疮性肾病中医辨证分型相关性的研究

LN is a common complication of SLE. Its therapy is a problem in medical field. Chinese herbs is effective to LN and can reduce the side effect of hormone,increasing the quality of life for LN patients. However , Syndrome differentiation and treatment is the essence of TCM, there are some factors that will affect the precision of Chinese diagnosis,like subjectivity, experience and lacking objectivity. molecular biological growth has influenced the Chinese medical field. Our group has found that the happening of LN and SLE has a close correlation of the regulation and expression of gene ACE and gene eNOS, Combined with the subject of diseases, 1000 cases of Hainan, northeast Han LN patients as the research object, through the epidemiology of /DME/ evidence-based medicine method combined with modern molecular biology techniques：① Analysis of clinical cases, the distribution characteristics of TCM Syndromes of LN observation;②apply high throughput SNP analysis ,studying the correlation of LN with gene ACE and eNOS；③the susceptibility of gene ACE and gene eNOS in the LN patients of the Han nationality. This study intends to establish a database for gene therapy from the aspects of gene level, regional association and the susceptibility of syndrome, which can provide a scientific basis for finding susceptibility gene and introducing gene therapy into LN treatment.

狼疮性肾病（LN）是系统性红斑狼疮常见并发症，其治疗仍困扰着医疗界。中医药对LN疗效确切,可减少激素样副作用,提高患者生存质量。辨证论治是中医学的精髓，而中医证候往往受医师的理论知识、临床经验等因素的影响。分子生物学在中医药研究中的应用为证候的规范化研究提供了科学的依据和思路。本课题组前期研究中发现LN发病与 ACE、eNOS调控和表达异常密切相关。本课题病证结合,以1000例海南、东北汉族LN患者为研究对象，通过流行病学/DME/循证医学方法结合现代分子生物学技术：①对临床病例进行分析，观察LN的中医证型的分布特征;②应用SNPScan分型技术，从基因水平探讨LN与基因ACE和eNOS的相关性；③探讨汉族LN中医证的易感性与ACE、eNOS基因多态性的关联。本研究拟从基因水平、地域关联、证的易感性等方面对基因治疗建立资料库，可为寻找证的易感基因、将基因治疗引入到LN证的治疗提供科学依据。

狼疮性肾病（LN）是困扰着医疗界的难题，中医药对LN疗效确切，可减少激素样副作用。辨证论治是中医学的精髓，而中医证候的确立缺乏客观性、规范性，分子生物学可为证候的规范化研究提供科学的方法和思路。本课题以1070例海南、东北汉族LN患者为研究对象，通过流行病学/DME/循证医学方法结合现代分子生物学技术研究发现：①东北地区患者中医证型以热毒炽盛证和阴虚内热证为主，而海南地区以脾肾阳虚证和阴虚内热证为主；②海南地区患者的ACE基因有两个位点rs4316和rs4362，eNOS基因有两个位点rs1808593和rs3918188，AGT基因两个位点rs5051和rs1926723，分别与LN的致病敏感性相关联；③东北地区ACE基因有四个位点rs4459609，rs4343、rs4316和rs4362，eNOS基因有两个位点rs1799983和rs3918188，AGT基因两个位点rs5051和rs1926723，与LN的致病敏感性相关联；④东北地区和海南地区患者有4个基因位点有差异，分别是ACE基因的rs4459609和rs4343，eNOS基因的rs1799983和rs1808593；⑤在LN患者中，ACE基因的rs4459609和rs4321可作为阴虚内热证的参考指标，eNOS基因的rs2070744可作为脾肾阳虚证参考指标，AGT基因的rs699、rs5051、rs4762可作为热毒炽盛证的参考指标。本研究从基因水平、民族关联、证的易感性等方面对基因治疗建立了资料库，并建立了LN的DNA资源库，验证了“微观辨证”及“辨证论治客观化”的学术思想，使LN证的研究标准化、科学化，为证的标准化研究提供资料。