小剂量骨化三醇对维持性血液透析患者骨保护素的影响

目的:分析小剂量骨化三醇对维持性血液透析(MHD)患者骨保护素(OPG)的影响。方法:选取90例MHD患者开展随机对照试验(RCT),采用随机数字表将纳入对象分为两组,基础组予以基础支持治疗,研究组在基础组方法治疗的同时采用小剂量骨化三醇治疗,共3个月。对比治疗前后血清OPG水平、骨密度T值变化,治疗期间骨质疏松症发生率及不良反应。结果:治疗后研究组血清OPG水平较治疗前升高(P<0.05),基础组治疗前后血清OPG水平比较差异无统计学意义(P>0.05),且治疗后研究组OPG高于基础组(P<0.05);治疗后两组骨密度T值均下降且研究组高于基础组(P<0.05),治疗期间研究组骨质疏松症发生率低于基础组(P<0.05);两组不良反应发生率差异无统计学意义(P>0.05)。结论:对MHD患者采用小剂量骨化三醇治疗可显著增加OPG水平,减少骨质疏松症且安全。     

血管紧张素Ⅱ灌注诱导大鼠肾脏血管紧张素转换酶2表达改变

目的 研究血管紧张素Ⅱ(AngⅡ)灌注后大鼠肾脏血管紧张素转换酶2(ACE2)表达的改变及其意义。 方法 雄性SD大鼠随机分为AngⅡ灌注组(400 ng&#8226;kg-1&#8226;min-1)、生理盐水灌注组和健康对照组，每组6只。测定28 天内大鼠血压及尿蛋白量变化。于第28天处死动物取肾，观察组织学改变，并用免疫组化、RT-PCR及Western印迹法检测ACE2表达及分布变化；凝胶电泳迁移率分析法(EMSA)检测核因子(NF)-κB的DNA结合活性变化。 结果 (1) AngⅡ灌注组大鼠血压升高，并出现明显蛋白尿。AngⅡ灌注后第28天，部分肾小球出现轻中度系膜增生，少数有节段性硬化；部分肾小管上皮细胞变性、坏死或萎缩，间质灶性炎性细胞浸润。(2) 健康大鼠肾脏ACE2主要分布于肾小管，以近端肾小管刷状缘分布最多。AngⅡ灌注后第28天，肾皮质ACE2 mRNA及蛋白表达均明显下降(P均< 0.05)，NF-κB结合活性显著增加(P < 0.05)。相关分析表明，ACE2表达与NF-κB结合活性之间呈负相关(r = -0.64，P < 0.01)。 结论 AngⅡ灌注可致大鼠肾脏ACE2表达明显下降，后者与肾损害的程度密切相关。肾脏ACE2表达下降可能是AngⅡ引起肾损害的重要机制     

骨化三醇预防大鼠原位肝移植后急性排斥的动态观察

目的探讨骨化三醇在预防大鼠原位肝移植后急性排斥反应中的作用。方法大鼠原位肝移植分为Wistar→Wistar同基因组 (Ⅰ组 ) ,SD→Wistar急性排斥组 (Ⅱ组 )和SD→Wistar环孢菌素治疗组 (Ⅲ组 ) ,SD→Wistar骨化三醇治疗组 (Ⅳ组 ) ,在移植后 1,5 ,7,15 ,30d各个时点检测肝脏功能、急性排斥反应、细胞因子表达等指标。结果Ⅳ组大鼠移植后 4 /6生存期大于 10 0d ,与Ⅱ组比较差异有显著意义 (P <0 0 0 1)。Ⅳ组大鼠移植后各时点平均AST(12 7± 4 1)U/L～ (36 0± 10 4 )U/L ,平均BIL(13± 5 )mmol/L～ (38± 11)mmol/L(与Ⅱ组比较 ,P <0 0 5 )。Ⅳ组移植后各时点平均排斥反应活动度积分 0分～ (3 3± 1 6 )分 (与Ⅱ组比较 ,P <0 0 5 )。Ⅳ组大鼠移植后各时点肝组织内IFN γmRNA表达明显减弱 ,IL 10mRNA表达明显增强 (与Ⅱ组比较 ,P <0 0 5 )。结论原位肝移植后骨化三醇治疗可以诱导细胞因子分泌向TH2型偏移 ,有效抑制急性排斥反应。     

血管紧张素转换酶2和血管紧张素转换酶基因多态性与妊娠期糖尿病相关性研究

目的探讨血管紧张素转换酶2(angiotensin converting enzyme 2,ACE2)单核苷酸多态性位点rs2285666及血管紧张素转换酶(angiotensin converting enzyme,ACE)插入/缺失(insertion/deletion,I/D)多态性与妊娠期糖尿病(GDM)的相关性。方法选取GDM孕妇360例,糖耐量受损(IGT)孕妇167例,以糖耐量正常(NGT)孕妇428例及50 g葡萄糖激发试验阴性[GCT(-)]孕妇273例[NGT+GCT(-)]为对照。共纳入受试者1,228例,采用聚合酶链反应(PCR)及聚合酶链反应-限制性片断长度多态性(PCR-RFLP)方法检测ACE2及ACE基因多态性。结果各组间ACE2 rs2285666和ACEI/D基因型及等位基因分布频率均无统计学差异(P>0.05)。GDM组ACE2 TT和ACE(DD+ID)基因型的组合TT(DD+ID)频率显著高于对照组(18.9%vs12.6%,P=0.005),具有TT(DD+ID)基因型者患GDM的危险性是具有其他基因型组合者的1.577倍[OR=1.577,95%CI(1.144～2.173)],通过logistic回归分析,校正年龄、血压、白细胞总数、甘油三脂的影响后,具有TT(DD+ID)基因型的孕妇患GDM的危险性是具有其他基因型组合者的1.699倍[OR=1.699,95%CI(1.129～2.556),Wald=6.46,P=0.011]。对照组中ACE基因型为(DD+ID)者的舒张压比ACE基因型为II者高[(68±9)mmHgvs(66±8)mmHg,t=2.635,P=0.009]。结论ACE2基因型TT和ACE基因型(DD+ID)的组合即TT(DD+ID)可能会增加妇女发生GDM的危险性,在正常妊娠妇女中携带ACE D等位基因者有相对较高的舒张压水平。     

阿法骨化醇冲击治疗血液透析患者甲状旁腺功能亢进

目的 研究维持性血液透析患者继发性甲状旁腺功能亢进,应用阿法骨化醇治疗效果及安全性.方法 对32例血液透析甲状旁腺功能亢进患者检测甲状旁腺素(iPTH)在360-2000pg/ml,进行血液透析加阿法骨化醇冲击治疗8-12周.结果 32例均有不同程度下降.其中1例因甲状旁腺腺瘤,甲状旁腺素下降不明显行手术治疗,1例血钙升高.结论 血液透析加阿法骨化醇冲击治疗效果明显,高钙血症发生率低,安全性耐受性好.     

帕立骨化醇对糖尿病肾病大鼠蛋白尿的影响

目的 研究维生素D类似物帕立骨化醇对糖尿病肾病(DN)大鼠蛋白尿的影响,并探讨其可能机制.方法 用链脲菌素(STZ)腹腔注射法构建DN大鼠动物模型,将造模成功的大鼠随机分为帕立骨化醇组(P组)、DN组(D组),并设置健康对照组(N组).给药12周后检测24 h尿蛋白量及血生化指标.用ELISA法检测肾组织肾素和血管紧张素Ⅱ(AngⅡ)水平.免疫组化和实时PCR检测肾小球基底膜乙酰肝素酶(HPA)、足细胞podocin蛋白及mRNA的表达.结果 D组和P组24h尿蛋白量、Scr、肾素及AngⅡ水平均显著高于N组,而D组显著高于P组,差异均有统计学意义(均P＜ 0.05).D组和P组HPA蛋白及mRNA表达均显著高于N组,而D组显著高于P组;D组和P组podocin蛋白及mRNA表达较低,D组显著低于P组,差异均有统计学意义(均P＜ 0.05).肾素水平与HPA蛋白表达呈正相关(r=0.78,P＜0.05);与podocin蛋白表达呈负相关(r=-0.63,P＜0.05);而与两者mRNA表达无相关.结论 帕立骨化醇可显著减少DN大鼠早期蛋白尿,其机制可能与通过抑制肾组织肾素表达,下调肾小球基底膜HPA,上调足细胞podocin蛋白表达有关.     

小剂量维生素D受体激活剂(骨化三醇)对血液透析患者血管紧张素Ⅱ和微炎症的影响

目的 探讨小剂量维生素D受体激活剂(骨化三醇)对血液透析患者血压、血管紧张素Ⅱ和微炎症的影响.方法 20例血液透析患者应用骨化三醇(0.25μg/d)治疗,分别于用药前、用药4、8周观察患者收缩压、舒张压、血浆血管紧张素Ⅱ、超敏C反应蛋白和白细胞介素6水平.结果 治疗4周后,患者收缩压与治疗前比较差异有统计学意义(P＜0.05);治疗4周后,患者血浆血管紧张素Ⅱ水平与治疗前比较差异有统计学意义(P＜0.05);治疗8周后,患者血浆超敏C反应蛋白水平与治疗前比较差异有统计学意义(P＜0.01);治疗4、8周后,患者血浆白细胞介素6水平与治疗前比较差异有统计学意义(P＜0.01).结论 小剂量维生素D受体激活剂(骨化三醇)对维持性血液透析患者可以明显降血压、抑制血管紧张素Ⅱ和抗炎症作用.     

骨化三醇冲击治疗血透患者继发性甲旁亢的疗效观察

目的：对照观察常规和不同冲击剂量的骨化三醇对维持性血透患者继发性甲旁亢（SHPT）的疗效.方法：选择我院63例血液透析患者分为常规组30例、治疗组33例,每组根据全段甲状旁腺素（iPTH）浓度再分为2个亚组,A1、B1组（300 pg/ml≤PTHi≤600 pg/ml）,A2、B2组（iPTH＞600 pg/ml）.常规组给予口服骨化三醇0.25 μg/d,治疗组分别给予口服骨化三醇2 μg/次、每周2次和2 μg/次、每周3次,治疗终点指标为iPTH≤300 pg/ml,或用药12周.分别测定治疗前及后第4周、8周、12周的iPTH、血钙、血磷、钙磷乘积和碱性磷酸酶（AKP）.结果：治疗8周时,A1组iPTH开始下降[（290.38±61.90）vs（452.53±91.09）,P＜0.05],治疗12周时iPTH继续下降,但与4周相比变化不大（P＞0.05）.A2组治疗8周时iPTH明显下降[（521.60±226.37）vs（926.13±226.07）,P＜0.01],治疗12周时iPTH又有所上升,但仍低于治疗前[（644.95±88.16）vs（926.13±226.07）,P＜0.05].冲击治疗组与常规治疗组相比,iPTH明显降低,钙磷乘积升高,患者临床症状改善,达标率高,差异有统计学意义.结论：骨化三醇冲击治疗对于继发性甲旁亢疗效显著,安全性好,值得推广.     

降钙素联合骨化三醇胶丸对糖尿病合并骨质疏松症的影响

目的探讨降钙素联合骨化三醇胶丸治疗糖尿病合并骨质疏松症患者对骨代谢、骨密度及血糖的影响。方法采用配对比较法将我院2011年1月至2015年12月收治的2型糖尿病合并骨质疏松症患者分为接受骨化三醇胶丸治疗的对照组及接受降钙素联合骨化三醇胶丸治疗的观察组,各40例。两组均接受基础降糖治疗,观察两组患者治疗前及治疗1年后骨代谢、血糖、骨密度情况和治疗期间的不良反应。骨代谢指标包括骨钙素(bone gamma-carboxyglutamic-acid-containing proteins,BGP)、β-胶原片段(beta-crosslaps,β-CTX)、25羟基维生素D[25-hydroxyvitamin D,25(OH)D]、人骨碱性磷酸酶(bone alkaline phosphatase,BALP)、甲状旁腺素(parathyroid hormone,PTH)。结果两组治疗前骨代谢指标、血糖指标及不同部位骨密度对比,差异无统计学意义(P0.05),观察组治疗1年后BGP、β-CTX、BALP、PTH低于同组治疗前及对照组同期(P0.05),25(OH)D及不同部位骨密度均高于同组治疗前及对照组同期(P0.05),空腹及餐后2 h血糖低于治疗前(P0.05),但与对照组相当(P0.05);观察组总有效率(97.50%)高于对照组(80.00%)(P0.05);两组不良反应发生率对比,差异无统计学意义(P0.05)。结论降钙素联合骨化三醇对糖尿病合并骨质疏松患者疗效显著,可有效改善骨代谢,治疗骨质疏松。     

骨化三醇联合钙尔奇D对老年女性2型糖尿病患者骨代谢的影响

目的探讨骨化三醇联合钙尔奇D对老年女性2型糖尿病患者骨代谢的影响。方法 2011年7月至2012年6月本院老年科及内分泌科45例≥65岁女性糖尿病住院患者,其中对照组23例,患者每晚口服1片钙尔奇D(疗程6个月),每片含碳酸钙1.5 g(相当于钙600 mg,维生素D3125IU);治疗组22例,患者每晚口服骨化三醇0.25μg联合1片钙尔奇D(疗程6个月),两组患者基础用药无明显差异,具有可比性。对比分析两组患者体重,腰围,BMI,血清血糖,血脂,肾功能,血钙,血磷,碱性磷酸酶,糖化血红蛋白,尿微量白蛋白/尿肌酐,Ⅰ型胶原羧基末端肽(CTx),Ⅰ型胶原氨基末端肽(PINP),右跟骨超声骨密度。结果两组患者体重、腰围、BMI,血糖、血脂、肾功能,糖化血红蛋白,尿微量白蛋白/尿肌酐参数均无统计学差异;而骨化三醇联合钙尔奇D治疗组患者的血钙水平明显高于对照组,差异有统计学意义(2.51±0.16 vs.2.08±0.15,P0.05);CTx明显低于对照组,差异有统计学意义(0.385±0.28 vs.0.644±0.31,P0.01);跟骨超声骨密度明显高于对照组,差异有统计学意义(0.618±0.108 vs.0.402±0.133,P0.05)。结论骨化三醇联合钙尔奇D明显降低老年女性2型糖尿病患者的骨吸收,改善骨代谢,增加骨密度。     

Intramuscular calcitriol for uraemic children with severe hyperparathyroidism and hypercalcaemia

The effect of intramuscular calcitriol was evaluated in five children (aged 1–16 years) with severe chronic renal failure and hyperparathyroidism [range of intact parathyroid hormone (PTH) 400–1,200 pg/ml]. All five children had been on oral calcitriol or 1-hydroxyvitamin D₃ treatment (5–20 ng/kg per day), but an adequate, efficacious dosage could not be achieved since any attempt of increasing the dosage resulted in severe hypercalcaemia (>2.9 mmol/l). Intramuscular calcitriol was given three times weekly for 5 months at an initial dosage of 65–70 ng/kg to all but one patient who received 100 ng/kg. In the first three patients, treatment resulted in an 86%–98% fall in serum PTH compared with baseline levels and serum calcium never exceeded 2.65 mmol/l, except for one episode of hypercalcaemia in one patient. In the last two patients, serum calcium rose above normal limits, thus calcitriol had to be discontinued several times and then restarted at a lower dosage (40 ng/kg); PTH fell by 61% and 73%, respectively, compared with basal values. All patients had very low pre-treatment levels of serum 1,25-dihydroxyvitamin D₃ (5–15 pg/ml) which were normalized (35–56 pg/ml) by the intramuscular calcitrioltreatment. Serum phosphorus and magnesium did not vary in any of the five patients. No side effects were observed at the injection site. Intramuscular calcitriol seems a useful therapeutic option for patients with severe hyperparathyroidism associated with a high serum calcium level when treated with conventional oral calcitriol.     

骨化三醇和氨基胍联合应用减轻大鼠肾移植急性排斥反应

目的探讨骨化三醇和氨基胍(AG)联合应用对大鼠肾移植急性排斥反应的作用。方法选取清洁级近交系健康雄性Wistar大鼠和SD大鼠为供、受者。实验随机分为5组,每组10只。Ⅰ组为同基因对照组:Wistar大鼠肾脏移植给Wistar大鼠,术前和术后不做任何处理;其余各组均为异基因移植,Wistar大鼠肾脏移植给SD大鼠,Ⅱ组为排斥对照组:术前和术后不做任何处理;Ⅲ组为氨基胍治疗组:手术当日开始腹腔注射氨基胍200mg/kg,2次/d,至实验结束;Ⅳ组为骨化三醇治疗组:术前1d开始腹腔注射骨化三醇1μg·kg-1·d-1,至实验结束;Ⅴ组为联合治疗组:氨基胍和骨化三醇联合应用,给药方案同Ⅲ、Ⅳ组。观察各组受者生存期和移植后5d肾组织病理学变化,检测血清肌酐、尿素氮、钙、磷以及γ干扰素(IFNγ)含量。结果Ⅰ～Ⅴ组受者存活时间分别为(9.1±1.9)d、(5.3±0.8)d、(9.7±2.1)d、(8.6±1.6)d和(12.9±3.4)d。Ⅴ组较Ⅱ～Ⅳ组生存期延长,差异有统计学意义(P<0.05)。Ⅲ、Ⅳ组受者存活期、移植肾排斥反应程度、肾功能及血清IFNγ表达水平较Ⅱ组明显改善或降低(P<0.01),Ⅴ组又较Ⅲ、Ⅳ效果更佳(P<0.05)。结论同种异体原位肾移植后联合应用用骨化三醇和氨基胍治疗可有效预防急性排斥反应,二者有明显的协同作用。     

Implications of intermittent calcitriol therapy on growth and secondary hyperparathyroidism

Secondary hyperparathyroidism is the most common skeletal lesion in pediatric patients undergoing maintenance dialysis. The present review summarizes a prospective randomized study that evaluated the biochemical and skeletal responses to intermittent calcitriol therapy in 33 pediatric patients on peritoneal dialysis with secondary hyperparathyroidism. Also, the effect of intermittent calcitriol therapy on linear growth was evaluated in 16 of 33 patients who had completed the clinical trial. Serum parathyroid hormone levels decreased by 62% from 648±125 pg/ml in patients treated with intermittent intraperitoneal (IP) calcitriol, and values remained unchanged from pre-treatment levels of 670±97 pg/ml with oral calcitriol therapy. Overall serum total and ionized calcium levels were higher in patients treated with IP calcitriol during the study. In contrast to these biochemical findings, the skeletal lesions of secondary hyperparathyroidism improved after 12 months of treatment in both groups and adynamic bone occurred in 33% of the patients. Z-scores for height decreased from –1.80±0.3 to –2.00±0.3, P<0.01, after 12 months of intermittent calcitriol therapy. Such findings suggest that an intermittent schedule of calcitriol administration adversely affects chondrocyte activity within epiphyseal cartilage in pre-pubertal children with end-stage renal disease. Received: 20 August 1999 / Revised: 2 February 2000 / Accepted: 9 February 2000     

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients

AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor(ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio(ACR) in urine. Genotyping of ACE I/D and AGT M235 T polymorphisms were performed by using primer specific polymerase chain reaction(PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients(responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric(≥ 30 and 300 mg/g creatinine) or macro-albuminuric(≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients(55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235 T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response(72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235 T polymorphisms.     

小剂量维生素D受体激活剂(骨化三醇)对血液透析患者血钙及血磷和成纤维细胞生长因子23的影响

目的 探讨小剂量维生素D受体激活剂(骨化三醇)对血液透析患者血钙、血磷和成纤维细胞生长因子23的影响.方法 20例血液透析患者应用骨化三醇(每天0.25μg)治疗,分别于用药前、用药4、8周观察患者血钙、血磷、碱性磷酸酶、全段甲状旁腺激素和成纤维细胞因子23水平.结果 用药4周和8周后患者血钙明显上升(但尚未超过正常范围),与治疗前比较差异有统计学意义(P＜0.01);用药4周和8周后血磷有所下降,但与治疗前比较差异无统计学意义(P＞0.05);用药4周和8周后血碱性磷酸酶明显下降,与治疗前比较差异有统计学意义(P＜0.01);用药4周后血全段甲状旁腺激素有所下降,但与治疗前比较差异无统计学意义(P＞0.05);用药4周和8周后血成纤维细胞因子23明显升高,与治疗前比较差异有统计学意义(P＜0.01).结论 小剂量维生素D受体激活剂(骨化三醇)对维持性血液透析患者具有升高血钙、抑制碱性磷酸酶并升高成纤维细胞生长因子23的作用.     

Renal angiotensin converting enzyme (ACE) expression in diabetic rats: the effect of ACE inhibitors]

Renal excreted angiotensin converting enzyme (ACE) inhibitor captopril, and renal.hepatic bile excreted ACE inhibitor temocapril, were compared by monitoring serum ACE and renal ACE expression (protein and mRNA) in streptozotocin-induced diabetic rats. Serum ACE levels did not change in untreated diabetic rats or in those treated with temocapril, compared with normal control rats. However, serum ACE levels significantly increased in diabetic rats treated with captopril after 3 months (153.8 +/- 23.0 vs. 43.5 +/- 5.5 IU/l/37 degrees C, p < 0.01) and 6 months (113.6 +/- 9.3 vs. 36.9 +/- 2.9 IU/l/37 degrees C, p < 0.01) compared with normal control rats. Compared with normal control rats (3.6 +/- 0.4), proximal tubular ACE protein expression significantly (p < 0.01) decreased in untreated diabetic rats (1.6 +/- 1.1), but significantly (p < 0.01) increased in diabetic rats treated with captopril (3.7 +/- 0.3) and temocapril (3.5 +/- 0.4). Renal ACE mRNA levels decreased in untreated diabetic rats (125.5 +/- 20.3 vs. 313.3 +/- 53.4, p < 0.01) compared with normal control rats for 6 months. Renal ACE mRNA levels tended to increase in diabetic rats treated with captopril (184.4 +/- 51.2 vs. 125.5 +/- 20.3) and temocapril (165.4 +/- 43.2 vs. 125.5 +/- 20.3) compared with untreated diabetic rats for 6 months. In conclusion, diabetic rats had lower proximal tubular ACE protein expression and lower renal ACE mRNA levels compared with normal control rats. Furthermore, both ACE inhibitors increased renal ACE protein and mRNA expression, but differed in their effect on serum ACE levels.     

Effects of prednisolone on angiotensin converting enzyme activity

Plasma angiotensin converting enzyme was measured in 23 asthmatic subjects before and after administration of prednisolone, 20 mg daily, for seven days. Plasma specimens from seven patients with asthma, seven with sarcoidosis and 14 normal subjects were also assayed before and after the addition of prednisolone in vitro. A plasma free extract of normal lung was also prepared and assayed before and after prednisolone treatment. Mean angiotensin converting enzyme activity was significantly greater in the asthmatic patients (40.3 nmol min-1 ml plasma-1) than in the control population (35.1 nmol min-1 ml plasma-1), though remaining within the 95% reference range. A fall in plasma angiotensin converting enzyme levels was seen after the addition of prednisolone in asthmatics both in vivo and in vitro. Similar in vitro falls were seen in patients with sarcoidosis but not in controls or in normal lung extract. No changes in angiotensin converting enzyme activity were seen after a single dose of 20 mg prednisolone in normal volunteers. Patients with asthma therefore appear to have higher mean angiotensin converting enzyme activities than the normal population and these fall after the addition of prednisolone whether this is added in vivo or in vitro.     

骨化三醇对高糖诱导的肾小管上皮细胞肾素高表达的影响

目的探讨骨化三醇对高糖状态下肾小管上皮细胞肾素表达的影响及其机制。方法按随机数字表法将24只6~8周龄Wistar大鼠随机分为对照组、糖尿病组、骨化三醇组(0.03μg·kg~(-1)·d~(-1)),各组8只。16周后处死各组大鼠,检测尿蛋白、尿肌酐、内生肌酐清除率(endogenous creatinine clearance rate,CCr),并应用实时荧光定量法(real time-polymerase chain reaction,RT-PCR)和蛋白印迹法(Western blot)检测肾脏组织肾素及磷酸化细胞外信号调节激酶(phosphorylated extracellularsignal-regulated kinase,p-ERK)/细胞外信号调节激酶(extracellularsignal-regulated kinase,ERK)表达情况。NRK-52E细胞分组:①正常对照组;②高糖组(糖浓度为25 mmol/L,不同时间点);③高糖+骨化三醇(10~8 mol/L、10~9 mol/L、10~10 mol/L)组;④高糖+ERK抑制剂(FR18020410~5 mol/L)组。RT-PCR法检测肾素mRNA表达,Western印记法检测肾素蛋白、p-ERK/ERK蛋白表达。结果与对照组比较,糖尿病组大鼠尿β2微球蛋白(β2-microglobulin,β2-MG)、尿白蛋白/尿肌酐升高(P0.05),CCr降低(P0.05);与糖尿病组比较,骨化三醇组大鼠尿β2-MG、尿白蛋白/肌酐降低(P0.05),CCr升高(P0.05)。与对照组比较,糖尿病组大鼠肾组织肾素、p-ERK/总ERK表达均明显升高,骨化三醇能显著减轻糖尿病大鼠上述蛋白的高表达(P0.05)。高糖可诱导NRK-52E细胞ERK蛋白磷酸化(P0.05),诱导肾素mRNA及蛋白表达上调,并呈时间依赖性(P0.05)。骨化三醇可浓度依赖性地降低高糖诱导的NRK-52E细胞ERK蛋白磷酸化及肾素mRNA、蛋白的高表达(P0.05)。ERK抑制剂能部分抑制高糖诱导的肾素蛋白高表达(P0.05)。结论骨化三醇降低糖尿病大鼠蛋白尿,具有肾脏保护作用,其机制可能与抑制ERK通路降低高糖诱导的肾素高表达有关。