气虚、阳虚体质与慢性原发性肾小球疾病中医证候及TGF-β相关性分析

【作者】 崔赵丽；

【导师】 王耀献；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2011， 博士

【摘要】 随着医学的进步和医学模式的变化,中医体质学越来越引起人们的重视,并积极开展了许多相关性研究。在慢性肾脏病中慢性原发性肾小球疾病是发病率较高的疾病,可以导致是终末期肾病(ESRD),造成生活质量和寿命的下降,给家庭以及社会带来沉重的精神和经济担,因此早期发现、治疗原发性肾小球病至关重要。然而肾脏疾病起病隐匿,在患病初期常常“无证可循”,而中医体质学研究在疾病的预防以及早期治疗中具有很大的优势,可以应用于原发性肾脏疾病的研究与治疗中。目的：通过随机抽样调查慢性原发性肾小球疾病患者的体质类型与其一般情况、中医证候、临床指标等资料,运用现代统计学方法,对不同体质类型原发性肾小球疾病患者临床证候与指标的相关性分析,探求不同体质类型在慢性原发性肾小球疾病中的临床特点,为中医药个体化防治慢性原发性肾小球疾病寻求客观依据,探索临床治疗的一种新思路。方法：对符合纳入标准的患者,进行体质调查问卷,收集,患者的一般情况、中医证候、临床指标等资料,运用现代统计方法,对于上述资料进行统计学分析,探求不同体质在本病中的基本特点。并且通过对血、尿样本的TGF-β的检测,结合体质与肾脏病理,分析其之间的相关性,为中医药个体化防治原发性肾小球疾病探索新思路。结果1.慢性原发性肾小球疾病中以气虚质、阳虚质和平和质最为常见。同时不同体质证候分布也存在一定的差异。气虚质患者的虚性证型中肺肾气虚证最常见(47.5%),其次为脾肾阳虚。阳虚质患者中的虚性证候以脾肾阳虚证最多(40.54%),其次为肺肾气虚证。平和质患者中虚性证候以肺肾气虚证作为主体(占46.88%)。气虚(阳虚)质与非气虚(阳虚)质虚性证候的分布存在统计学意义。实性证型以湿热和湿浊最为多见,在各种体质中分布差异不明显。2.根据尿液蛋白检测结果,气(阳)虚体质与尿蛋白定性分级呈显著正相关,且阳虚质尿蛋白水平远远高于其他体质类型。血尿素氮、白蛋白、甘油三酯水平在各体质组间差异显著,P＜0.05。血肌酐水平以阳虚质最高,平和质最低,且阳虚质与气虚质、平和质之间差异性显著(P＜0.05)。血浆白蛋白以气虚质组最高,且与其余各体质组间差异明显,具有统计学意义(P＜0.05)。其他体质组(包括阴虚质、痰湿质、湿热质、瘀血质、特禀质)甘油三酯水平最高,其次为气虚质,且阳虚质、气郁质、平和质与其他体质组差异性性显著(P＜<0.01)。总胆固醇水平以其他体质组最高,其次为气郁质,阳虚质最低且与其他体质组间差异性显著(P＜0.01)。补体C3水平各组间差异明显(P＜0.05),以阳虚质最高,平和质和气郁质最低,两两比较,平和质与气虚质、阳虚质组间差异明显(P＜<0.05),气郁质与气虚质组比较差异明显(P＜0.05)。3.平和质中系膜增生性和膜性肾病患者最多,各占平和质例数的37.5%。气虚质中,以系膜增生性肾病为主,占42.1%。阳虚质中,局灶增生硬化性肾病最多,共占40.6%,各组间分布无明显差异。但其中阳虚质与平和质相比较,病理类型分布差异明显,P＜0.05,有统计学意义。4. TGF-β在患者患病时尿液中含量明显高于正常人。血TGF-β1水平在各类肾脏病理类型中,以局灶增生硬化性肾病含量高1533.35±789.52pg/m1,其次为微小病变患者1512.90±774.72 pg/ml,且局灶增生硬化性肾病和微小病变肾损伤血TGF-β1水平分别与系膜增生性肾病和膜性肾脏具有显著性差异,P＜0.05。从体质学角度来看,血TGF-β1水.平在各组间差异明显,P＜0.05,具有统计学意义。其中气虚质血TGF-β1水平最高,为1503.63±757.97pg/m1,平和质和阳虚质最低,分别为947.90±642.35pg/m1和929.76±596.54pg/m1,且气虚质与平和质和阳虚质患者相比,差异有统计学意义,P＜0.05。5.TGF-β与肾功能、血脂、血凝、血常规等指标无相关性。血TGF-β与血中IgA、IgM,尿TGF-β与血中IgA、IgG存在正向相关,尿TGF-β与补体C3存在负向相关性。经逐步回归分析,血TGF-β与IgM的回归方程为：y=713.526+344.86x,方程有统计学意义(P=0.01)；尿TGF-β与IgG的回归方程为：y=64.423+12.12x,方程有统计学意义(P＜0.01)结论：①慢性原发性肾小球疾病中存在体质类型的差异,且不同体质的临床证候、临床资料、病理等方面均存在各自的特点,其中阳虚质患者病情较重；②本病患者生长转化因子一β1可以升高,且与肾脏病理、体质类型存在不同的相关性,且在本病初期,TGF-β1的升高除与肾脏增生纤维化相关,可能与免疫调节关系密切。③气虚质患者与本病的关联主要体现在免疫功能方面,可能与TGF-β在本病早期的免疫调节作用有关。更多还原

【Abstract】 With advances in medicine and change of medicine model,it is interested by more and more people about the theory of constitute of TCM, and actively carried out a lot of correlated research. Chronic primary glomerular disease is a kind of prevalent kidney disease, and is the main cause of the end stage renal disease (ESRD).,which resulting in the decline of quality of life and age, bringing huge economic burden to the family and the society. So it is very important to.early discovery and treatment. However kidney disease onset conceals, it is hard to differentiate symptoms and signs in initial stage.The theory of constitute of TCM has a great advantage in the prevention of disease and early treatment of chronic kidney disease, and can be applied to research and treatment of primary kidney disease.Objective: By observing the constitution, the people general state of health, sydrome and symptoms, clinical indicators of chronic primary glomerular disease by sampling survey with random, we try to analyze the correlation between these by mordern statistics, to explore the clinical characteristics between different type of constitution in chronic idiopathic glomerular disease for, TCM individualized prevent and treat chronic primary glomerular disease.By this way,we try to find a new way to prevent and cure chronic primary glomerular disease.Methods:by observing the general state of health, sydrome and symptoms, clinical indicators of the people meeting the inclusion standards, filling in questionnaire of constitution,applying modern statistical methods, explore the different physical characteristics in different constitution in the disease. And through observe the level of TGF-βin the serum and urine of primary glomerular diseases, combined with the constitution and kidney pathological, analyzing the correlation between it, we try to find a new way to prevent and cure chronic primary glomerular disease.Results:1. Deficiency Qi of constitution, Deficiency Yang of constitution, and normal constitution is more common in Chronic primary glomerular disease. At the same time different constitutions have distribution of syndrome. Deficency of lung qi and kidney qi syndrom can be seen as usually from deficency of qi constitution(47.5%).The second syndrom can be seen in this constitution is deficency of spleen yang and kidney yang syndrom.In deficency of yang constitution the most syndrome is deficency of spleen yang and kidney yang syndrom (40.54%), and secondly is deficency of lung qi and kidney qi syndrom. Yang, the virtual qualitative patients with spleen and kidney Yang syndrome (most 40.54% issuing), lung kidney deficiency syndrome.The most syndrome in constitution is deficency of lung qi and kidney qi syndrom. There were statistically significant with difference between deficiency of qi and yang constitutions and not these constitutions. The syndrome of excess were no differences,and the most frequent is syndrome of dampness and heat and syndrome of dampness.2.According to results of proteinuria, deficiency of qi and yang constitutions with gallery level of proteinuria has conspicuous correlation. And urea nitrogen, creatinine and triglyceride in serum has conspicuous difference between various constitutions(p<0.05). In creatinine level the highest is difficiency of yang constitution, the least is normal constitution. And there are conspicuous difference between difficiency of yang constitution and deficiency of qi constitution, normal constitution (p<0.05). Deficiency of qi constitution is the highest in the level of plasma-albumin.and exist conspicuous differences with the other constitutions(p<0.05). Other constitutions group has the highest level of triglyceride and cholesterol, and exist conspicuous differences. There are different level of complement C3 between various constitutions (p<0.05).And the highest is difficiency of yang constitution,the minimun is normal constitution and stagnation of qi constitution in level of complement C3.Meanwhile, normal constitution with difficiency of yang constitution, difficiency of qi constitution has apparent difference(p<0.05), stagnation of qi constitution with difficiency of qi constitution has apparent difference(p<0.01).3. Mesangial proliferative glomerulonephritis(37.5%) and membranous nephropathy (37.5%) is the most in normal constitution.In difficiency of qi constitution, the most is also mesangial proliferative glomerulonephritis(42.1%).And in difficiency of yang constitution, the most is sclerosing glomerulonephritis (40.6%).Compare with normal constitution and difficiency of yang,the difference is remarkable in distribution of type of pathology(p<0.05)4.TGF-beta level in patients of chronic primary glomerular disease is 163.99±67.42,which is higher than healthy people(p<0.01).The level of TGF-beta in serum is the highest in sclerosing glomerulonephritis, the second in minimal change nephropathy. And these two types of pathology is predominance difference compared with MPG and MN(p<0.05).From aspect of constitute of TCM, The level of TGF-beta in serum is difference in various constitution(p<0.05),which has statistical significance.And difficiency of qi constitution has the highest level of TGF-beta in serum.normal constitution and difficiency of yang,the difference is the minimum.Meanwhile these distribution has significance in statistic(p<0.05).5. The level of TGF-beta in serum relates to IgA. IgM. The level of TGF-beta in urine relates to lgA. lgG,and is negative correlation to complement C3.According to gradual regressive analysis, regression equation of the level of TGF-beta in serum and IgM is y=713.526+344.86x, the regression equation of The level of TGF-beta in urine and IgG is y=64.423+12.12x.Conclusions:(1) There are differences in various constitutions. And different constitution has respectively characters in the aspects of syndrome, symtoms, clinical index, type of pathology,and so on. Pathogenetic condition is heavier in the difficiency of yang constitution. (2)TGF-beta level in patients of chronic primary glomerular disease can increase,and exist different correlation about type of pathology and constitution.At same time, the raising of TGF-beta may be relate to immunologic mechanism,except procedure of fibration. (3)The relationship with difficiency of qi constitution and this disease, may be reflect to aspect of immune by TGF-beta.更多还原