糖皮质激素受体DNA甲基化对脾肾阳虚型原发性肾病综合征患者激素敏感性的影响及“加减金匮肾气丸”干预作用的研究  

The Effect of GR DNA Methylation to GC Sensitiveness in Asdthenic Splenonephro-yang Primary Nephrotic Syndrome Patients and the In-tervention of “Addition and Subtraction of Jinkui Shenqi Wan”

作　　者：张盈[1] 陈红波[2] 鲁科达[2] 张培培[2] 何灵芝[2] 

机构地区：[1]浙江中医药大学第一临床医学院,杭州310053 [2]浙江中医药大学附属第一医院

出　　处：《浙江中医药大学学报》2015年第5期340-344,共5页Journal of Zhejiang Chinese Medical University

基　　金：浙江省卫生厅项目(2011KYB059)~~

摘　　要：[目的]1探讨糖皮质激素受体(glucocorticoid receptor,GR)DNA甲基化对脾肾阳虚型原发性肾病综合征(primary nephrotic syndrome,PNS)患者糖皮质激素(glucocorticoid,GC)敏感性的影响,以分析PNS GC耐药的机制;2探讨中药"加减金匮肾气丸"对脾肾阳虚型PNS患者GC治疗的干预作用,分析其缓解肾病的机理,确定中医药的临床疗效,为进一步优化治疗方案奠定基础。[方法]收集2010年至2013年我院收治的120例脾肾阳虚型PNS患者,根据病情给予GC及对症治疗8周,根据GC治疗反应分Ⅰ组(GC敏感)和Ⅱ组(GC抵抗)各60例,再将Ⅱ组随机分为对照组及治疗组各30例,对照组继续予GC及对症治疗,治疗组在对照组治疗基础上加服免煎中药颗粒"加减金匮肾气丸",连续治疗16周。治疗结束后所有患者均检测血清GR水平、外周血单个核细胞(peripheral blood mononuclear cells,PBMC)GR m RNA水平、GR DNA甲基化水平,并定期检测患者24h尿蛋白定量(24h urinary protein,24h UP)、血清白蛋白(albumin,Alb)、血肌酐(serum creatinine,Scr)的变化。[结果]1II组血清GR-α浓度低于I组,GR-β浓度及DNA甲基化转移酶(DNA methyltransferase,DNMTs)水平均明显高于I组,差异有统计学意义(P<0.05);II组GR-αm RNA水平低于I组(P<0.05),GR-βm RNA及DNMTs m RNA水平均高于I组,差异无统计学意义(P>0.05)。2治疗组血清GR-α浓度及GR-αm RNA表达水平均高于对照组(P<0.05),两组间GR-β及DNMTs差异无统计学意义(P>0.05)。3治疗组和对照组治疗后24h UP明显减少,Alb明显提高,差异有统计学意义(P<0.05);治疗组24h UP较对照组下降更明显,差异有统计学意义(P<0.05);治疗组Alb较对照组升高更明显,差异有统计学意义(P<0.05);两组Scr治疗前后差异无统计学意义(P>0.05)。[结论]1脾肾阳虚型PNS患者的血清GR-α和GR-β浓度及PBMC GR-α和GR-β的m RNA表达存在异常,其表达紊乱可能是造成GC耐药的原因之一。2中药"加减金匮肾气丸"对脾肾阳虚�Objective] ①To investigate the effect of glucocorticoid receptor（GR） DNA methylation to glucocorticoid（GC） sensitiveness and the mechanism of GC-resistance in asdthenic splenonephro-yang primary nephrotic syndrome（PNS） patients. ②To explore the intervention effect of“Addition and subtraction of Jinkui Shenqi Wan”in asdthenic splenonephro-yang PNS patients with GC therapy and its mechanism. [Method] Collect 120 cases of asdthenic splenonephro-yang PNS patients treated in our hospital from 2010 to 2013.Treat them with GC and symptomatic treatment for 8 weeks. Then divide them into 2 groups according to the GC response： Group I（GC sensitive） and Group II（GC resistance）, 60 cases in each of them. Randomly assign the Group II into the treatment group treated with “addition and subtraction of Jinkui Shenqi Wan”and the control group treated without “addition and subtraction of Jinkui Shenqi Wan”.After 16 weeks of GC and symptomatic treatment, detect the level of serum GR ,peripheral blood mononuclear cells （PBMC） GR,GR DNA methylation of all patients. Regularly test the change of 24h urinary protein（24hUP） ,serum albumin（Alb）,serum creatinine（Scr） of all patients. [Results] ①It has significant difference that the GC resistance group has lower level of serum GR-α and higher level of GR-β and DNA methyltransferase（DNMTs）（P〈0.05） than the GC sensitive group. There is no difference that the GC resistance group has lower GR mRNA expression（ P〈0.05） and higher level of GR-βand DNMTs（P〉0.05） than the GC sensitive group. ②The treatment group has higher level of serum GR-αand GR mRNA expression than the control group（P〈0.05）.There is no difference of GR-βand DNMTs between the two groups（P〉0.05）.③The rise of Alb（P〈0.05） and the decrease of 24hUP（P〈0.05） can be found in both of the treatment group and the control group. And the treatment group has a more obvious trend of 24hUP decrease and Alb increase than the control gr

关 键 词：DNA甲基化 耐药 金匮肾气丸 脾肾阳虚 临床研究 

分 类 号：R692[医药卫生—泌尿科学]