青藤碱对MsPGN大鼠肾脏病理及ICAM-1表达的影响

为探讨青藤碱(Sinomenine,SIN)对实验性系膜增生性肾小球肾炎(MsPGN)的病理形态学改善及肾组织中细胞间粘附分子-1(ICAM-1)表达的影响,通过实验建立改良的慢性血清病性MsPGN动物模型,光镜观察肾小球以及肾小管-间质的病理改变情况,采用免疫组织化学法检测ICAM-1的表达并分别进行半定量分析。结果显示:光镜下,模型组与正常组相比,系膜基质指数显著升高(P<0.01),肾小球毛细血管直径明显缩小(P<0.01);青藤碱组与模型组相比,上述病理改变明显减轻,系膜基质指数显著下降(P<0.01),肾小球毛细血管直径明显改善(P<0.01)。肾组织中ICAM-1免疫组化结果显示青藤碱可明显下调ICAM-1的表达,肾组织ICAM-1的相对含量、积分光密度,均显著下降(P<0.01),青藤碱组与雷公藤多苷组相比,二者无统计学意义(P>0.05)。实验表明青藤碱能够有效减轻肾脏病理损害,抑制MsPGN大鼠肾组织ICAM-1的表达,延缓疾病进展。     

I型纤溶酶原激活物抑制物在紫癜肾炎肾组织中的表达

为研究I型纤溶酶原激活物抑制物(PAI-1)在紫癜肾炎病理机制中的作用.采用免疫组织化学和原位杂交方法检测了23例紫癜肾炎患者肾组织中的PAI-1.结果证实:在正常肾组织内和紫癜肾炎肾组织内均可检测到PAI-1表达,PAI-1mRNA原位杂交阳性信号主要分布于血管平滑肌细胞和肾小管上皮细胞内,紫癜肾炎肾小球内有紫兰色阳性信号,且强度与肾小球内细胞的增生程度有关.     

血清IL-8在过敏性紫癜的表达及意义

目的:研究血清白介素-8(IL-8)在过敏性紫癜(HSP)中的表达及意义。方法:采用酶联免疫吸附试验(ELISA)检测和比较过敏性紫癜急性期(包括紫癜性肾炎、非紫癜性肾炎)患儿、过敏性紫癜恢复期患儿、健康体检儿童血清IL-8的含量。结果:过敏性紫癜急性期患儿血清IL-8含量显著高于过敏性紫癜恢复期患儿和健康儿童(P0.05),而过敏性紫癜恢复期、健康儿童血清IL-8含量比较无统计学差异(P0.05)。紫癜性肾炎患儿、非紫癜性肾炎患儿的血清IL-8含量均明显高于健康儿童,且非紫癜性肾炎血清IL-8含量显著低于紫癜性肾炎患儿(P0.05)。结论:急性期过敏性紫癜患儿血清IL-8含量上调,可能参与了过敏性紫癜的发生,并可能与紫癜性肾炎的发生有关。     

慢性肾小球肾炎患者血清MMP-9和TIMP-1的浓度及意义

目的:观察慢性肾小球肾炎血清基质金属蛋白酶9(matrix metalo protein-ase-9,MMP-9)、金属蛋白酶组织抑制剂1(tissue inhibitors of metalloproteinases,TIMP-1)的浓度与肾组织中MMP-9、TIMP-1表达的相关性,探讨慢性肾小球肾炎血清MMP-9、TIMP-1对肾脏纤维化的判断价值。方法:通过肾组织活检病理检查,将入选慢性肾炎的病例分增生组(A组)15例,纤维化组(B组)15例,另选10例志愿者作为健康对照组C组。应用免疫组化法观察A、B两组MMP-9、TIMP-1在肾组织中的表达情况,并且进行半定量分析,比较它们之间有无差别。应用ELISA双抗体夹心法检测A、B、C三组MMP-9、TIMP-1在血清中的浓度,比较它们之间有无差别。观察A、B两组MMP-9、TIMP-1在肾组织中的表达水平与在血清的浓度有无相关性。结果:A、B两组MMP-9在肾小球和肾间质少见表达,主要在肾小管上皮细胞浆中表达增高,两组之间表达的强度有显著差异性;A组TIMP-1在肾小球中少见表达,在肾小管上皮细胞增强。B组TIMP-1在肾小球中有少量表达,在肾小管上皮细胞较A组进一步增强,两组之间表达的强度有显著差异性(P0.05)。血清中MMP-9、TIMP-1浓度在A、B组显著高于C组,血清中MMP-9在A、B两组之间无显著差异性,血清中TIMP-1在A、B、C三组间两两比较有显著差别(P0.05)。结论:慢性肾炎患者血清中MMP-9、TIMP-1浓度与肾脏组织中MMP-9、TIMP-1的表达呈正相关。MMP-9、TIMP-1的相关性分析P值小于0.01。血清MMP-9、TIMP-1参与了肾脏纤维化的进展,慢性肾小球肾炎血清中MMP-9、TIMP-1的浓度可在一定程度上反映肾脏纤维化程度。     

Ⅰ型纤溶酶原激活物抑制物在紫癜肾炎肾组织中的表达

为研究Ⅰ型纤溶酶原激活物抑制物（PAI-1）在紫癜肾炎病理机制中的作用。采用免疫组织化学和原位杂交方法检测了23例紫癜肾炎患肾组织中的PAI-1。结果证实,在正常肾组织内和紫癜肾炎肾组织蚋均可检测到PAI-1表达,PAI-1mRNA原位杂交阳性信号主要分布于血管平滑肌细胞和肾小管上皮细胞内,紫癜肾炎肾小球内有紫兰色阳性信号,且强度与肾小球内细胞的增生程度有关。     

转化生长因子-β蛋白及mRNA基因在人类系膜增生性肾小球肾炎中的表达

目的：探讨转化生长因子－β（TGF－β）蛋白及mRNA基因在系膜增生性肾小球肾炎中的表达及其在发病中的作用。方法：采用常规病理,免疫组织化学及原位杂交方法对人系膜增生性肾小球肾炎组织进行染色,并经医学图像分析系统进行分析,结果：在正常对照组,TGF－β蛋白及TGF－β1mRNA小肾小管上皮细胞呈极弱表达,肾小球内TGF－β蛋白及mRNA未见阳性表达,在系膜增生肾小球肾炎组织中,TGF－β蛋白在肾近曲小管上皮细胞胞浆内呈强阳性表达,肾小球球囊壁及系膜区呈阳性,肾小球与肾小管阳性表达与正常对照组相比均具有显性差异（P＜0．01）,TGF－β1mRNA阳性表达位于肾近曲小管上皮细胞胞浆内和肾小球系膜区,肾小球和肾小管上皮细胞TGF－β1mRNA阳性表达与正常对照组相比差异也有显性（P＜0．01）。结论：系膜增生性肾小球炎时TGF－β蛋白及TGF－β1mRNARNA阳性表达与正常对照组相比差异也有显性（P＜0．01）。结论：系膜增生性肾小球肾炎时TGF－β蛋白及TGF－β1mRNA在肾小球与肾小管表达均显增高,进一步显示TGF－β在肾小球系膜细胞增生及肾小管间质纤维化中所起的重要作用。     

树突状细胞C型凝集素DC-SIGN在人肾炎组织和肾小管上皮细胞表达

DC-SIGN(DC-specificICAM-grabbingnon-integrin,亦称CD209)属树突状细胞(DC)表面C型凝集素的膜蛋白。作为DC黏附及模式识别受体,其参与介导了DC的炎症组织迁移,识别捕获病原微生物,以及随后激活静息T细胞启动的免疫应答。为此观察了DC-SIGN及DC-SIGN DC在肾炎患者肾组织中表达和分布,以及DC-SIGN在炎性状态下培养人肾小管上皮细胞表达,探讨与肾小管间质炎症病变和损伤的关系。结果显示,DC-SIGN在正常肾组织基本不表达,而在肾炎早期即以肾小管上皮细胞为主表达上调,且随肾小管间质病变程度加重表达增强(P<0.01),与肾小管间质病变程度明显相关(P<0.01)。此外,DC-SIGN在经TNF-α刺激炎性状态下的人肾小管上皮细胞也明显表达。进一步发现,DC-SIGN DC在肾炎早期以肾间质为主分布聚集,也随肾小管间质病变程度加重明显增多(P<0.01),与肾小管间质病变程度显著相关(P<0.01),也与DC-SIGN表达相关联(P<0.01)。另外,DC-SIGN DC在肾小管间质分布数量与肾炎患者肾功能改变明显相关(P<0.05)。研究结果提示,DC-SIGN也是肾小管间质早期炎症的启动参与因素,其介导DC可能也参与了人肾炎肾小管间质的免疫损伤机制。     

Wnt/β-catenin信号通路与儿童过敏性紫癜的相关性观察

该文旨在观察Wnt/β-catenin信号通路在儿童过敏性紫癜(Henoch-Schonlein purpura,HSP)中的表达,并探讨了该信号通路在HSP中的作用及可能机制。应用免疫组化法检测HSP患儿皮肤和过敏性紫癜性肾炎(Henoch-Schnlein purpura nephritis,HSPN)患儿肾脏组织中Wnt4、β-catenin和E-cadherin的表达,同时对HSPN患儿的24 h尿蛋白定量与肾组织中Wnt4、β-catenin和E-cadherin的表达做相关性分析。免疫组织化学结果显示,HSP组患儿皮肤中,Wnt4、β-catenin表达量较正常对照组表达量显著增多(P0.01),E-cadherin表达量较正常对照组显著减少(P0.01)。HSPN患儿肾脏组织中,Wnt4、β-catenin表达量较正常对照组表达量显著增多(P0.01),主要表达在肾小管;Ecadherin表达量较正常对照组显著减少(P0.01)。HSPN患儿肾脏组织中,E-cadherin表达量与24 h尿蛋白定量呈负相关(R=–0.695,P0.05)。该研究结果提示,Wnt4、β-catenin和E-cadherin在HSP患儿皮肤和HSPN患儿肾脏组织中均有异常表达,肾组织中E-cadherin表达量与尿蛋白有相关性,推测Wnt/β-catenin信号通路可能参与了HSP的发病。     

低氧诱导因子在肾炎大鼠肾小管间质中的表达及氯沙坦的保护作用研究

目的:观察低氧诱导因子在肾炎大鼠肾小管间质中表达的变化以及氯沙坦对肾炎的保护作用。方法:雄性Wistar大鼠32只,随机分成假手术组、肾炎模型组、氯沙坦小剂量组、氯沙坦大剂量组各8只,假手术组不做肾脏切除,其他组在右肾切除后尾静脉注射标记抗体。给药组则按量分别灌胃给药,8周时处死。结果:大剂量给药组的血肌酐(Scr)、收缩压和24 h尿蛋白量较模型组显著降低,且小剂量给药组的血肌酐(Scr)和24h尿蛋白量较模型组也显著降低。小剂量组和大剂量组大鼠的肾间质面积较肾炎模型组均显著降低。HIF-1αmRNA大量表达于肾小管上皮细胞胞质和间质细胞胞质,且与模型组比较,小剂量给药组的HIF-1αmRNA显著降低;大剂量给药组较肾炎模型组HIF-1αmRNA的含量也显著降低。结论:氯沙坦可能可以通过影响低氧诱导因子(HIF-1α)的表达发挥对肾脏的保护作用。     

大鼠5/6肾切除慢性肾功能衰竭动物模型的实验研究

观察5/6肾切除大鼠模型中肾功能、肾脏病理改变、肾组织α-平滑肌肌动蛋白(α-SMA)表达的变化,证明5/6肾切除可制作理想的慢性肾功能衰竭、肾间质纤维化动物模型。方法:大鼠随机分为假手术组(SOR)和5/6肾切除组。随机选取各组中的10只大鼠分别于5/6肾切除术后30、60和90天处死,收集血清与肾组织供生化及病理分析。结果:①5/6肾切除组24小时尿蛋白定量、血尿素氮、血肌酐水平明显高于假手术组(P<0.05)。②残肾的肾重/体重逐渐增加,到术后90天时,几乎接近假手术组大鼠左肾肾重/体重。③5/6肾切除后,残肾肾小球面积和肾小球毛细血管体积增加,肾小球硬化指数(GSI)及肾小管间质损伤评分(TIS)明显高于假手术组(P<0.05)。④免疫组化结果显示,5/6肾切除组肾间质和小管上皮细胞α-SMA表达增加。⑤肾小球面积、GSI、α-SMA表达与血肌酐、蛋白尿水平呈明显正相关性。结论:5/6肾切除可以建立伴慢性肾功能衰竭的肾间质纤维化动物模型。     

特发性膜性肾病患者外周血中性粒细胞-淋巴细胞比值的临床与病理价值分析

摘要 目的：探讨外周血中性粒细胞与淋巴细胞比值（NLR）在特发性膜性肾病（IMN）中的临床及病理价值。方法：收集2017年1月至2019年12月确诊为IMN患者221例作为IMN组,将2019年7月至2019年9月体检且尿常规和肾功能指标正常的87例健康体检者作为正常对照组,计算每个研究对象的NLR值,比较两组间NLR值的差异。记录IMN患者的血生化指标及患者的肾脏病理分期及纤维化程度,并且根据MDRD公式计算肾小球滤过率(eGFR),分析NLR与IMN患者的血生化指标及病理特征的相关性。ROC曲线分析外周血NLR评估IMN患者肾间质纤维化的敏感性和特异性。结果：IMN组外周血NLR值高于对照组,差异有统计学意义（P<0.05）。外周血NLR值与IMN患者年龄和肾间质纤维化有关联（P均<0.05）,但与IMN患者性别及肾脏病理分期无关联（P均>0.05）。IMN外周血NLR值与IMN患者hs-CRP、SCr、BUN呈正相关（P<0.05）,与eGFR呈负相关（P<0.05）,与ESR、UA、TP、Alb、24小时蛋白尿定量均无相关性（P均>0.05）。不同程度肾间质纤维化的IMN患者外周血NLR值不同,差异有统计学意义（P<0.05）,且肾间质纤维化程度在1、2、3级时,纤维化程度越重,NLR值越大;3个级别间两两比较,差异均有统计学意义（P均<0.05）。外周血NLR值预测IMN患者肾间质纤维化的ROC曲线下面积为0.715[95%CI(0.626,0.803)],其截断值为1.858时,灵敏度为68.6%,特异度为66.7%。结论：外周血NLR可作为IMN肾脏功能水平的一个有效评价指标,且与IMN患者肾间质纤维化有关,可作为判断肾间质纤维化的参考指标。     

Circulating TNF Receptors 1 and 2 Are Associated with the Severity of Renal Interstitial Fibrosis in IgA Nephropathy

The current study aimed to examine whether the levels of TNF receptors 1 and 2 (TNFR1 and TNFR2) in serum and urine were associated with other markers of kidney injury and renal histological findings, including TNFR expression, in IgA nephropathy (IgAN). The levels of the parameters of interest were measured by immunoassay in 106 biopsy-proven IgAN patients using samples obtained immediately before renal biopsy and in 34 healthy subjects. Renal histological findings were evaluated using immunohistochemistry. The levels of serum TNFRs were higher in IgAN patients than in healthy subjects. The levels of both TNFRs in serum or urine were strongly correlated with each other (r > 0.9). Serum TNFR levels were positively correlated with the urinary protein to creatinine ratio (UPCR) and four markers of tubular damage of interest (N-acetyl-β-D-glucosaminidase [NAG], β2 microglobulin [β2m], liver-type fatty acid-binding protein [L-FABP], and kidney injury molecule-1 [KIM-1]) and negatively correlated with estimated glomerular filtration rate (eGFR). Patients in the highest tertile of serum TNFR levels showed more severe renal interstitial fibrosis than did those in the lowest or second tertiles. The tubulointerstitial TNFR2-, but not TNFR1-, positive area was significantly correlated with the serum levels of TNFRs and eGFR. Stepwise multiple regression analysis revealed that elevated serum TNFR1 or TNFR2 levels were a significant determinant of renal interstitial fibrosis after adjusting for eGFR, UPCR, and other markers of tubular damage. In conclusion, elevated serum TNFR levels were significantly associated with the severity of renal interstitial fibrosis in IgAN patients. However, the source of TNFRs in serum and urine remains unclear.     

尿铜蓝蛋白、肾损伤因子1与糖尿病肾病患者肾功能的关系及对预后不良的预测价值研究

摘要 目的：探讨尿铜蓝蛋白（CP）、肾损伤因子1（KIM-1）与糖尿病肾病（DKD）患者肾功能的关系及对预后不良的预测价值。方法：回顾性分析2017年1月～2019年1月陆军第八十二集团军医院肾内科收治的160例DKD患者（DKD组）的临床资料,随访3年,根据是否发展为终末期肾脏疾病（ESRD）分为预后不良组42例和预后良好组118例,另选取同期56例单纯2型糖尿病（T2DM）患者作为T2DM组和47例体检健康者作为对照组。采用微量法和酶联免疫吸附试验法检测尿CP、KIM-1水平,并计算尿白蛋白/肌酐比值（UACR）和估算肾小球滤过率（eGFR）。通过Spearman相关性分析DKD患者尿CP、KIM-1与UACR、eGFR的相关性,单因素和多因素Logistic回归分析DKD患者预后不良的影响因素,受试者工作特征（ROC）曲线分析尿CP、KIM-1对DKD患者预后不良的预测价值。结果：随访3年,160例DKD患者有42例发展为ESRD,预后不良发生率为26.25％（42/160）。DKD组尿CP、KIM-1、UACR高于T2DM组、对照组,eGFR低于T2DM组、对照组（P＜0.05）;T2DM组尿CP、KIM-1、UACR高于对照组,eGFR低于对照组（P＜0.05）。Spearman相关性分析显示,DKD患者尿CP、KIM-1与UACR呈正相关（P均＜0.001）,与eGFR呈负相关（P均＜0.001）。多因素Logistic回归分析显示,高血压、DKD分期4期和糖化血红蛋白（HbA1c）（较高）、低密度脂蛋白胆固醇（LDL-C）（较高）、UACR（较高）、尿CP（较高）、尿KIM-1（较高）为DKD患者预后不良的独立危险因素（P＜0.05）,eGFR（较高）为独立保护因素（P＜0.05）。ROC曲线分析显示,尿CP、KIM-1联合预测DKD患者预后不良的曲线下面积大于各指标单独预测。结论：DKD患者尿CP、KIM-1升高与肾功能降低和预后不良密切相关,尿CP、KIM-1联合预测DKD患者预后不良的价值较高。     

Predictive Usefulness of Urinary Biomarkers for the Identification of Cyclosporine A-Induced Nephrotoxicity in a Rat Model

The main side effect of cyclosporine A (CsA), a widely used immunosuppressive drug, is nephrotoxicity. Early detection of CsA-induced acute nephrotoxicity is essential for stop or minimize kidney injury, and timely detection of chronic nephrotoxicity is critical for halting the drug and preventing irreversible kidney injury. This study aimed to identify urinary biomarkers for the detection of CsA-induced nephrotoxicity. We allocated salt-depleted rats to receive CsA or vehicle for 7, 14 or 21 days and evaluated renal function and hemodynamics, microalbuminuria, renal macrophage infiltration, tubulointerstitial fibrosis and renal tissue and urinary biomarkers for kidney injury. Kidney injury molecule-1 (KIM-1), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), fibronectin, neutrophil gelatinase-associated lipocalin (NGAL), TGF-β, osteopontin, and podocin were assessed in urine. TNF-α, IL-6, fibronectin, osteopontin, TGF-β, collagen IV, alpha smooth muscle actin (α -SMA) and vimentin were assessed in renal tissue. CsA caused early functional renal dysfunction and microalbuminuria, followed by macrophage infiltration and late tubulointerstitial fibrosis. Urinary TNF-α, KIM-1 and fibronectin increased in the early phase, and urinary TGF-β and osteopontin increased in the late phase of CsA nephrotoxicity. Urinary biomarkers correlated consistently with renal tissue cytokine expression. In conclusion, early increases in urinary KIM-1, TNF-α, and fibronectin and elevated microalbuminuria indicate acute CsA nephrotoxicity. Late increases in urinary osteopontin and TGF-β indicate chronic CsA nephrotoxicity. These urinary kidney injury biomarkers correlated well with the renal tissue expression of injury markers and with the temporal development of CsA nephrotoxicity.     

兔慢性肾功能衰竭模型的建立与评价

目的建立兔慢性肾功能衰竭模型,为干细胞移植治疗和相关研究奠定基础。方法普通级大耳白兔随机分为正常对照组和单侧输尿管结扎（unilateral ureteral obstruction,UUO）组。UUO组于输尿管结扎后2、4、6、8周进行血生化肾功能指标检测,并取肾组织观察肾脏病理学改变,通过SPECT动态观察肾小球滤过率的变化,采用免疫组织化学方法观察肾组织转化生长因子-β1（TGF-β1）的表达情况。结果①UUO组术后第2周,出现明显的血肌酐升高,尿素氮术后第8周开始升高（P〈0.01）。②UUO组术后第4周,肾脏组织出现了早期间质纤维化的病理改变,术后第8周肾小球开始出现硬化,间质纤维化明显,皮质明显变薄。术后第12周,肾小球硬化比例增加,肾小管玻璃样变性,间质纤维化进一步加重（P〈0.05）。③SPECT动态观察肾小球滤过率,UUO组第4周GFR值比正常对照组降低,到第8周时,GFR值进一步下降,结扎侧肾脏功能降低甚至丧失。④免疫组织化学染色显示,TGF-β1在术后第4、8、12周均明显增强,并且各时间点表达均有显著差异（P〈0.05）。结论单侧输尿管结扎法成功制作比较稳定的慢性肾功能不全模型,UUO后第8周符合肾脏间质纤维化模型标准。     

The Uremic Toxin Adsorbent AST-120 Abrogates Cardiorenal Injury Following Myocardial Infarction

An accelerated progressive decline in renal function is a frequent accompaniment of myocardial infarction (MI). Indoxyl sulfate (IS), a uremic toxin that accumulates from the early stages of chronic kidney disease (CKD), is contributory to both renal and cardiac fibrosis. IS levels can be reduced by administration of the oral adsorbent AST-120, which has been shown to ameliorate pathological renal and cardiac fibrosis in moderate to severe CKD. However, the cardiorenal effect of AST-120 on less severe renal dysfunction in the post-MI setting has not previously been well studied. MI-induced Sprague-Dawley rats were randomized to receive either AST-120 (MI+AST-120) or were untreated (MI+Vehicle) for 16 weeks. Serum IS levels were measured at baseline, 8 and 16 weeks. Echocardiography and glomerular filtration rate (GFR) were assessed prior to sacrifice. Renal and cardiac tissues were assessed for pathological changes using histological and immunohistochemical methods, Western blot analysis and real-time PCR. Compared with sham, MI+Vehicle animals had a significant reduction in left ventricular ejection fraction (by 42%, p<0.001) and fractional shortening (by 52%, p<0.001) as well as lower GFR (p<0.05) and increased serum IS levels (p<0.05). A significant increase in interstitial fibrosis in the renal cortex was demonstrated in MI+Vehicle animals (p<0.001). Compared with MI+Vehicle, MI+AST-120 animals had increased GFR (by 13.35%, p<0.05) and reduced serum IS (p<0.001), renal interstitial fibrosis (p<0.05), and renal KIM-1, collagen-IV and TIMP-1 expression (p<0.05). Cardiac function did not change with AST-120 treatment, however gene expression of TGF-β1 and TNF-α as well as collagen-I and TIMP-1 protein expression was decreased in the non-infarcted myocardium (p<0.05). In conclusion, reduction of IS attenuates cardio-renal fibrotic processes in the post-MI kidney. KIM-1 appears to be a sensitive renal injury biomarker in this setting and is correlated with serum IS levels.     

芪地固肾方对膜性肾病大鼠肾组织足细胞裂孔隔膜蛋白Nephrin和Podocin表达的影响

摘要 目的：探讨芪地固肾方治疗膜性肾病（MN）大鼠的效果及其可能的机制。方法：将40只SD雄性大鼠随机分为模型组（等剂量生理盐水尾静脉注射）、雷公藤多甙片组（10 mg/kg雷公藤多甙片）、芪地固肾方低剂量组（15.425 g/kg芪地固肾方）、芪地固肾方高剂量组（61.7 g/kg芪地固肾方）四组,另取10只未造模大鼠作为空白组（等剂量生理盐水尾静脉注射）,连续干预28天后,检测24小时尿蛋白定量（U-TP）、血清总蛋白（TP）、白蛋白（ALB）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、血肌酐（Scr）、尿素氮（BUN）的变化;HE染色、透射电镜观察大鼠肾组织病理学改变;RT-PCR检测肾组织中nephrin蛋白、podocin mRNA的表达。结果：与空白组比较,模型组24 hU-TP、足细胞nephrin和podocin mRNA显著升高,血清TP和ALB显著降低（P<0.01）;与模型组比较,各给药组24 hU-TP降低,血清TP和ALB显著升高（P<0.05）;肾组织免疫复合物沉积减少,肾小球基底膜增厚减轻;足细胞nephrin和podocin mRNA表达升高（P<0.05）。结论：芪地固肾方能够降低MN模型大鼠的尿蛋白水平,减轻肾脏病理损伤,上调肾组织中足细胞裂孔隔膜蛋白nephrin和podocin mRNA的表达,延缓膜性肾病的进展。     

Molecular Markers of Tubulointerstitial Fibrosis and Tubular Cell Damage in Patients with Chronic Kidney Disease

In chronic kidney disease (CKD), progressive nephron loss causes glomerular sclerosis, as well as tubulointerstitial fibrosis and progressive tubular injury. In this study, we aimed to identify molecular changes that reflected the histopathological progression of renal tubulointerstitial fibrosis and tubular cell damage. A discovery set of renal biopsies were obtained from 48 patients with histopathologically confirmed CKD, and gene expression profiles were determined by microarray analysis. The results indicated that hepatitis A virus cellular receptor 1 (also known as Kidney Injury Molecule-1, KIM-1), lipocalin 2 (also known as neutrophil gelatinase-associated lipocalin, NGAL), SRY-box 9, WAP four-disulfide core domain 2, and NK6 homeobox 2 were differentially expressed in CKD. Their expression levels correlated with the extent of tubulointerstitial fibrosis and tubular cell injury, determined by histopathological examination. The expression of these 5 genes was also increased as kidney damage progressed in a rodent unilateral ureteral obstruction model of CKD. We calculated a molecular score using the microarray gene expression profiles of the biopsy specimens. The composite area under the receiver operating characteristics curve plotted using this molecular score showed a high accuracy for diagnosing tubulointerstitial fibrosis and tubular cell damage. The robust sensitivity of this score was confirmed in a validation set of 5 individuals with CKD. These findings identified novel molecular markers with the potential to contribute to the detection of tubular cell damage and tubulointerstitial fibrosis in the kidney.