Objective To investigate the expression and distribution of Cdc42-interacting protein 4 (CIP4) in renal fibrotic tissue,and the interaction between CIP4 and β-catenin in transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) model of HK-2 cell line.Methods In vivo,the model of renal fibrosis was induced by 5/6 subtotal nephrectomy in rat.Masson staining was used to evaluate the level of renal tissue fibrosis.The expression and distribution of CIP4 was detected by immunohistochemistry.In vitro,the EMT model of HK-2 cell line was induced by TGF-β1 (10 μg/L) for 72 h.Western blotting was used to observe the expression of E-cadherin,β-catenin,CIP4 and α-SMA.Colocalization and interaction of CIP4 and β-catenin were detected by immunofluorescence and immunoprecipitation respectively.Results Compared to sham group,CIP4 expression was increased in group of 5/6 subtotal nephrectomy,CIP4 was mainly distributed in basolateral side of renal tubular epithelia.In vitro,expressions of α-SMA and CIP4 were increased in HK-2 cells stimulated by TGF-β1 for 72 h (2.5and 1.8 folds,respectively) (all P＜0.05),expression of E-cadherin was decreased(P＜0.05).Partial colocalization between CIP4 and β-catenin was detected by immunofluorescence.In control group,CIP4 and β-catenin partially colocalized at the cell membrane.Mter the stimulation of TGF-β1,translocation to nucleus of CIP4 and β-catenin were increased,and partially colocalized in nucleus.The interaction between CIP4 and β-catenin was observed by immunoprecipitation in both control and TGF-β1 stimulated groups.Conclusions Expression of CIP4 in renal fibrotic tissue is increased,which is mainly distributed in basolateral side of renal tubular epithelia.CIP4 and βcatenin partially colocalize and interact with each other.CIP4 may play a role in EMT process through the interaction with β-catenin.

Epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal interstitial fibrosis, which finally leads to renal failure. Erbin, a member of LAP family, is recently reported to inhibit Smads and ERK pathway which are two important types of intracellular signaling involved in TGF-β1-induced EMT. However, the role of Erbin in the regulation of EMT and the underlying mechanisms remain to be fully understood. To that end, we aimed to evaluate the expression of Erbin in renal interstitial fibrosis and the potential role of Erbin in tubular EMT stimulated by TGF-β1. In this study we demonstrated that the expression of Erbin was upregulated in the tubular epithelia of 5/6-nephrectomized rats. We also showed here that TGF-β1 upregulated Erbin expression in NRK52E cells during their EMT phenotype acquisition. Importantly, elevated expression of Erbin inhibited ERK signaling and partial reversed EMT stimulated by TGF-β1. In the mean time, reducing Erbin expression enhanced ERK phosphorylation, promoted the E-cadherin suppression, and induced α-SMA expression and fibronection secretion in response to TGF-β1, which could be rescued if cells were treated with the inhibitor of MEK1/2 U0126. However, in the absence of TGF-β1, Erbin failed to affect ERK activation and EMT process. These results suggest that Erbin is a negative feedback molecule induced by TGF-β1 and inhibits TGF-β1-induced EMT via ERK signaling pathway.

Cdc42-interacting protein-4 (CIP4) is an F-BAR (Fer/CIP4 and Bin, amphiphysin, Rvs) family member that regulates membrane deformation and endocytosis, playing a key role in extracellular matrix (ECM) deposition and invasion of cancer cells. These processes are analogous to those observed during the initial epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. The role of CIP4 in renal tubular EMT and renal tubulointerstitial fibrosis was investigated over the course of the current study, demonstrating that the expression of CIP4 increased in the tubular epithelia of 5/6-nephrectomized rats and TGF-β1 treated HK-2 cells. Endogenous CIP4 evidenced punctate localization throughout the cytosol, with elevated levels observed in the perinuclear region of HK-2 cells. Subsequent to TGF-β1 treatment, CIP4 expression increased, forming clusters at the cell periphery that gradually redistributed into the cytoplasm. Simultaneously, EMT induction in cells was confirmed by the prevalence of morphological changes, loss of E-cadherin, increase in α-SMA expression, and secretion of fibronectin. Overexpression of CIP4 promoted characteristics similar to those commonly observed in EMT, and small interfering RNA (siRNA) molecules capable of CIP4 knockdown were used to demonstrate reversed EMT. Cumulatively, results of the current study suggest that CIP4 promotes TGF-β1-induced EMT in tubular epithelial cells. Through this mechanism, CIP4 is capable of inducing ECM deposition and exacerbating progressive fibrosis in chronic renal failure.

Objective To explore the effect of JNK-c-Jun signal pathway on connexin 43 (Cx43) expression and its role in renal tubular epithelial-myofibroblast transition (TEMT) induced by TGF-β1. Methods Normal rat kidney tubular epithelial cells (NRK-52E) were cultured in Dulbecco's modified eagle medium (DMEM) with 10％ fetal bovine serum,then were randomly divided into 3 groups: control group,TGF-β1 group (treated with TGF-β1 10 μg/L),and TGF-β1+SP600125 (selective JNK inhibitor,50 μmol/L) group. The protein expressions of JNK,c-Jun,α-SMA,Cx43 and E-cadherin were assayed by immunocytochemistry and Western blotting.The Cx43mRNA was assayed by RT-PCR.Gap junction intercellular communication (CJIC) was measured by fluorescence recovery after photobleaching assay (FRAP). Results TGF-β1 increased the expressions of JNK,c-Jun and α-SMA (P＜0.05),reduced the expressions of Cx43 and E-cadherin (P＜0.05),and inhibited GJIC of NRK-52E (P ＜0.05).SP600125 could alleviate the above expressions changes and enhanced GJIC induced by TGF-β1. Conclusion JNK-c-Jun signal pathway induces TEMT of NRK-52E treated with TGF-β1 via down-regulation of connexin 43expression and inhibition of GJIC.

目的 分析凝固酶阴性葡萄球菌(CNS)的耐药性,比较苯唑西林耐药的CNS(MRCNS)与苯唑西林敏感的CNS(MSCNS)的药物敏感性.方法 收集2007年1～12月临床分离CNS,琼脂纸片扩散法检测其对9种抗菌药物的敏感性,MRCNS的检测采用头孢西丁纸片法,诱导性克林林霉素耐药的检测采用D实验.结果 共分离出CNS 678株,检出MRCNS 296株,占43.7%,诱导性克林林霉素耐药72株,占10.7%.MRCNS对红霉素的耐药率高速94.9%,对复方磺胺甲恶唑的耐药率为70.3%,对环丙沙星、克林霉素和四环素的耐药率在63.7%～69.3%,对庆大霉素的耐药率较低,为20.7%,与MSCNS比较差异有统计学意义.MRCNS与MSCNS对青霉素的耐药率均>90%,未见对替考拉宁和万古霉素耐药菌株.结论 CNS引起的感染日益增多;MRCNS对常用抗菌药物的耐药率高于MSCNS,糖肽类抗菌药物是治疗MRCNS的首选药物;临床抗感染治疗应依据抗菌药物敏感试验合理用药.

【Objective】 To study the relationship between Biliverdin reductase(BVR) and tubular interstitial vessels in the kidney of 5/6 nephrectomized rats.【Methods】 Chronic renal failure was induced by 5/6 nephrectomy.Immunohistochemical SABC and Western blot methods were used to detect the expression of BVR at 12 weeks,immunofluorescence confocal Laser Scanning Microscopy was used to detect the expression of BVR and its relationship of the tubular interstitial vessels.【Results】 When renal fibrosis occurred,tubular interstitial vessels of kidney were destroyed.The expression of BVR in the renal epithelium of 5/6 nephrectomized rats increased in contrast with sham group at 12 weeks,and there were significant correlations between BVR and tubular interstitial vessels: high density of tubular interstitial vessels with low expression of BVR,while low density of that with higher expression of BVR.【Conclusions】 BVR expressed non-homogeneously in kidney,when renal fibrosis occurred,tubular interstitial vessels of kidney were destroyed,accompanied with higher expression of BVR.

Objective To observe the effect of CIP4(Cdc42 interacting protein 4)on human renal tubular epithelial to mesenchymal transition(EMT)induced by transforming growth factor β1(TGF-β1)and to study the associated mechanism. Methods Human proximal tubular epithelial cells (HK-2 cell line) were cultured with TGF-β1 (10μg/L) for 72 hours. The protein expressions of E-cadherin and α-SMA were measured by Western blotting. One set of siRNA oligos specific for CIP4 and CIP4 construction of the entire coding sequence were designed based on the full CIP4 sequence in GenBank. Then HK-2 cells were transfected with CIP4-siRNA or pcDNA3.1-hCIP4 via lipofactamine 2000. The protein expressions of CIP4, E-cadherin and α-SMA were evaluated respectively in control cells, TGF-β1 treated cells, siRNA transfected cells, pcDNA3.1-hCIP4-transfected cells by Western blotting. The distribution of E-cadherin and α-SMA was observed by confocal microscope. After TGF-β1-treated HK-2 cells were interferenced with specific inhibitor of PI3K-Akt (wortmannin) 1μmol/L for 48 hours, Western blotting was used to detect the CIP4 protein in control cells and interferenced cells. Results With TGF-β1 stimulation, the expression of E-cadherin protein was decreased markedly (P＜0.05), and in contract, the expression of α-SMA were increased notably (P＜0.05), which revealed that TGF-β1 could induce EMT. After transfected with CIP4-siRNA, the protein expression of E-cadherin was increased (P＜0.05), and the protein expression of α-SMA was decreased (P＜0.05). The EMT induced by TGF-β1 was effectively reversed. After transfected with pcDNA3.1-hCIP4, the expression of E-cadherin protein was down-regnlated (P＜0.05), and the expression of α-SMA protein was up-regulated compared with control group (P＜0.05), leading to EMT. After HK-2 cells were interferenced with wortmannin for 48 hours, the expression of CIP4 was decreased (P＜0.05). Conclusion TGF-β1 upregulates the expression of CIP4 via PI3K-Akt pathway, and CIP4 may participate in EMT induced by TGF-β1.

Objective To investigate the expression of Erbin in renal interstitial fibrosis (RIF) and the effect of over-expression of Erbin on transforming growth factor β1 (TGF-(β1)-induced epithelial-mesenchymal transition (EMT) in NRK52E cells. Methods In vivo, the model of renal fibrosis was induced by 5/6 subtotal nephrectomy in rat. Scr and BUN was detected and Masson staining was used to evaluate the level of renal tissue fibrosis. The location and expression of Erbin in renal tissue were detected by immunohistochemistry and Western blotting. In vitro, after NRK52E cells were treated by TGF-β1 (10 μg/L) for 72 h, immunofluorescence and Western blotting were used to obverse the expression and distribution of E-cadherin and α-SMA. The expression of Erbin mRNA and protein were detected by RT-PCR and Western blotting respectively. NRK52E cells were transiently transfected with Prk5-myc-Erbin plasmid via lipofectamine 2000, then the expressions of Erbin, E-cadherin and α-SMA were detected by Western blotting. Results (l)Compared to sham group with Scr (33.96±7.28) μmol/L and BUN (8.11±2.55) mmol/L, rats in 5/6 nephrectomy model with Scr (140.52±61.11) μmol/L and BUN (34.23±7.66) mmol/L revealed renal dysfunction. Masson staining indicated kidney interstitial fibrosis, and the expression of Erbin was significantly increased in renal tissue(2.9 folds), especially in tubular epithelia. (2)In vitro, the expressions of Erbin and α-SMA were markedly increased (2.3 folds and 2.1 folds, P<0.05, respectively) and the expression of E-cadherin was dramatically decreased in NRK52E cells stimulated by TGF-β1, which were consistent with immunofluorescence results. TGF-β1-induced E-cadherin suppression and a-SMA induction could be efficiently blocked by over-expression of Erbin (all P <0.05). Conclusions Erbin is up-regulated in renal interstitial fibrosis, and over-expression of Erbin can partly inhibit renal EMT induced by TGF-β1, which indicates Erbin playing an protective role in renal fibrosis.

Background. The p38 mitogen-activated protein kinase (p38 MAPK) is an important intracellular signal transduction pathway involved in TGF-β1-induced epithelial–mesenchymal transition (EMT). Sema4C, a member of the semaphorin family, was found to be essential for the activation of p38 MAPK. However, the role of Sema4C in promoting TGF-β1-induced EMT is unclear. Methods. Renal fibrosis was induced by 5/6 subtotal nephrectomy rat model. In vitro, Sema4C was induced in human proximal tubular epithelial cells (HKC) by treatment with TGF-β1, or was inhibited by siRNA or was over-expressed by Sema4C transfection. The selective p38 MAPK inhibitor, SB203580, was administered to inhibit the p38 pathway. The expression of Sema4C, the markers of EMT, p38 phosphorylation and fibronectin secretion were measured by western blotting, immunohistochemistry, immunocytochemistry or enzyme-linked immunosorbent assay. Results. The expression of Sema4C increased in HKC cells that were treated with TGF-β1. Knockdown of Sema4C potently inhibited phosphorylation of p38 MAPK and reversed TGF-β1-induced EMT. Over-expression of Sema4C via Sema4C transfection elicited p38 MAPK phosphorylation and promoted EMT. The effects of Sema4C during EMT were blocked by a p38-specific inhibitor. In vivo, the expression of Sema4C increased in the tubular epithelia of 5/6-nephrectomized rats and human fibrotic renal tissue, and similar localization of phosphorylated p38 and Sema4C was demonstrated by immunohistochemistry on serial sections. Conclusions. Our findings suggest that Sema4C plays an important role in TGF-β1-induced EMT through activation of p38 MAPK in proximal tubular epithelial cells.

Recently,phosphatase and tensin homolog deleted on chromosome 10(PTEN) is suggested as a new agent in the fighting against fibrogenesis.In tumor,DJ-1 is identified as a negative regulator of PTEN.But the expression of DJ-1 and the regulation of PTEN in fibrosis are unclear.Renal fibrosis was induced in 5/6 subtotal nephrectomy rat model.Human proximal tubular epithelial cells(HKC) were treated with transforming growth factor-beta 1(TGF-β1),or transfected with DJ-1 or PTEN.Confocal microscope was used to investigate the localization of DJ-1 and PTEN.The selective phosphoinositide-3 kinase(PI3K) inhibitor,LY294002,was administered to inhibit PI3K pathway.The DJ-1 and PTEN expression,markers of epithelial-mesenchymal transition(EMT) and Akt phosphorylation were measured by RT-PCR,Western blotting or immunocytochemistry.In vitro,after HKC cells were stimulated with 10 ng/mL TGF-β1 for 72 h,the expression of DJ-1 was increased,and that of PTEN was decreased.In vivo,the same results were identified in 5/6-nephrectomized rats.In normal HKC cells,most of DJ-1 protein localized in cytoplasm,and little in nucleus.TGF-β1 upregulated DJ-1 expression in both cytoplasma and nuclei.In contrary,TGF-β1 emptied cytoplasmic PTEN protein into nucleus.Overexpression of DJ-1 decreased the expression of PTEN,promoted the activation of Akt and the expression of vimentin,and also led to the loss of cytoplasmic PTEN.Contrarily,overexpression of PTEN protected HKC cells from TGF-β1-induced EMT.In conclusion,DJ-1 is upregulated in renal fibrosis and DJ-1 mediates EMT by suppressing cytoplasmic PTEN expression and Akt activation.

Objective To observe the expression and localization of CIP4 (Cdc42 interacting protein-4) in the renal fibrosis and the effect of CIP4 on the expression of E-cadherin,vimentin and β-catenin tyrosine phosphorylation. Methods In vitro, the human tubular epithelial cells (HK-2 cell line) were cultured with 10 μg / L TGF-β1 for 72 h. The protein expressions of CIP4, E-cadherin, vimentin and β-catenin tyrosine phosphorylation were measured by Western blotting; the expression of CIP4 mRNA was detected by RT-PCR. The intracellular distribution of CIP4 was observe by confocal microscope. In vivo, Masson staining was used to evaluate the level of renal fibrosis; the expression and distribution of CIP4 in renal tissue were detected by immunohistochemistry. HK-2 cells were transfected with pcDNA3. 1-CIP via lipofectamine 2000. The expressions of E-cadherin, vimentin and β-catenin tyrosine phosphorylation level in the transfected cells were detected by Western blotting. Results The expressions of CIP4 mRNA and protein were up-regulated in renal tubular EMT cells. Most of CIP4 protein localized in cell membrane, and some was in cytoplasm. After stimulation by TGF-β1, the expression of CIP4 protein both in cytoplasm and nucleus was greatly increased (P ＜0.05),especially in cytoplasm. In vivo, CIP4 was expressed in renal tubular epithelia, but little expressed in glomeruli. In renal from 5/6 nephrectomized rats, CIP4 expression was significantly increased. In the CIP4 transfectants, the expression of CIP4, vimentin and β-catenin tyrosine phosphorylation level were up-regulated (P ＜0.05), but E-cadherin expression was suppressed (P ＜0.05).Conclusion The overexpression of CIP4 is likely to take part in the epithelial-to-mesenchymal transition process, thereby promoting the renal fibrosis.

BACKGROUNDTransforming growth factor ß1 (TGF-ß1), connective tissue growth factor (CTGF) and Smad7 are potent components of fibrogenesis-related signal transduction pathways. Renal fibrosis is the major pathological change in the rat models with unilateral ureteral obstruction (UUO). Investigating the effects of gypenosides (GPs) on the expression of fibrogenesis-related genes in the UUO model may lead to the development of effective therapy for renal diseases.METHODSRats were randomly divided into 3 experimental groups: (i) sham operation rats treated with saline (sham group), (ii) UUO model rats treated with saline (control group) and (iii) UUO model rats treated with GPs (GPs group). Blood urea nitrogen and serum creatinine were detected as the measurement of renal function. UUO-treated kidney tissues were taken for assessment of renal damage index and determination of related gene expression through immunohistochemistry and RT-PCR.RESULTSUUO-induced tubulointerstitial damage and fibrosis were attenuated by the application of GPs (day 3 and day 7, p<0.01; day 14, p<0.05). The expression of TGF-ß1 and CTGF was significantly reduced with GPs treatment (TGF-ß1, p<0.01; CTGF, p<0.05). Smad7 expression was elevated with GPs treatment at days 7 and 14 (p<0.01). GPs' protective effects on renal function were also demonstrated with this UUO model.CONCLUSIONSThese results suggest that UUO-induced tubulointerstitial fibrosis can be effectively attenuated by GPs application. GPs-mediated down-regulation of TGF-ß1 and CTGF and up-regulation of Smad7 are essential for their effects of antifibrogenesis.

目的:观察含白蛋白透析液(alburnjn dialysis,AD)治疗急性重度有机磷中毒合并多器官功能障碍综合征(MODS)的临床疗效,并与血液灌流(hemoperfusion,HP)作比较.方法:19例急性重度有机磷中毒合并MODS患者,在一般治疗基础上,联合应用血液净化治疗:9例行AD,以4000 ml质量浓度4%白蛋白溶液作透析液,封闭循环使用,10例行HP.观察患者的意识恢复清醒时间、胆碱酯酶(ChE)恢复时间、阿托品的总用量、病死率及治疗前、后平均动脉压(MAP)、血小板计数和肿瘤坏死因子(TNF-α)的变化.结果:AD组患者意识恢复清醒时间、ChE恢复时间、阿托品的总量、病死率低于HP组(P＜0.05),治疗后AD组MAP上升、TNF-α下降与HP组相比有统计学意义(P＜0.05),血小板无明显下降,患者临床症状与体征改善,优于HP组.结论:白蛋白透析治疗急性重度有机磷中毒合并MODS疗效显著.

目的 研究曲尼司特(tranilast,Tran)对转化生长因子-β1(TGF-β1)刺激人肾小管上皮细胞(HKCs)表达结缔组织生长因子(CTGF)的影响,以探讨其抗肾小管间质纤维化的机制.方法 将培养的HKCs,按随机化分为:①对照组,②TGF-β1(5 ng/m1)干预组,③TGF-β1(5 ng/ml)+Tran(100μmol/L)干预组.免疫荧光检测爬片细胞的磷酸化Smad2(PSmad2)蛋白的表达,用RT-PCR方法评价CTGF mRNA的表达,Western blot方法评价CTGF和胶原Ⅵα蛋白的表达.结果 TGF-β1刺激30 min时,HKCs的细胞核PSmad2蛋白的表达明显增强,TGF-β1+Tran干预组PSmad2蛋白的表达明显下降(P<0.05),对照组细胞核未见明显PSmad2蛋白的表达.在48 h时,TGF-β1干预组HKCs的CT-GF mRNA、CTGF和胶原Ⅵα蛋白表达明显高于对照组(均P<0.05),而TGF-β1+Tran干预组则明显下降(均P<0.05).结论 曲尼司特可能是一个很有潜力的抗肾间质纤维化的药物,其机制是通过抑制TGF-β1诱导的CTGF的表达及其下游的Smad2信号通路的激活而发挥作用.

目的 观察曲尼司特联合贝拉普利对5/6肾切除大鼠肾脏的保护作用,并探讨其机制.方法 将50只雄性SD大鼠随机分为5组:假手术组(S组)、5/6肾切除模型组(M组)、曲尼司特干预组(T组)、贝拉普利干预组(B组)和曲尼司特联合贝拉普利干预组(C组),每组10只.术后第12周观察各组大鼠体重、血压、尿蛋白量、血肌酐及肾组织病理改变,用逆转录聚合酶链反应(RT-PCR)法检测残肾组织转化生长因子β1(TGF-β1)mRNA的表达,Western blotting法检测残肾组织Ⅲ型胶原蛋白的表达.结果 与S组相比,M组大鼠血压、尿蛋白量和血肌酐水平明显升高,肾小球硬化、肾间质纤维化程度加重,残肾组织.TGF-β1 mRNA和Ⅲ型胶原蛋白的表达升高,差异均有统计学意义(P＜0.05).与M组相比,T组和B组上述指标减轻,差异均有统计学意义(P＜0.05).与T组和B组相比,C组均更明显地减轻上述指标,差异均有统计学意义(P＜0.01).结论 曲尼司特联合贝拉普利对5/6肾切除大鼠的肾脏有更佳的保护作用,其机制可能与其减轻TGF-β1引起的细胞外基质的沉积有关.

急性重度生物毒素中毒可引起多器官功能障碍综合征(MODS),常累及肾脏、肝脏、心脏、大脑及血液系统等,病情凶险,可迅速发展为多器官功能衰竭(MOF),病死率很高.本院采用一种新的血液净化技术--单向白蛋白透析滤过(SPADF)抢救重度生物毒素中毒取得了较好疗效,现将治疗体会报告如下.

Objective To investigate the effect and safety of tranilast in early-stage diabetic nephropathy. Methods Twenty patients with early-stage diabetic nephropathy were divided into two groups at random.The tranlist treated group were administered with tranlist 100 mg,tid for 12 months,and the control group received no tranlist.If the blood pressure consistently increased,added no more ACEI and ARB,used calcium channel blocker,β receptor blocker and /or diuretics instead,to control blood pressure 140/90 mmHg.The clinical data were collected and evaluated before and 3,6,9,12 months after treatment. Results Both urinary type IV collagen excretion and albumin decreased significantly (P0.05) after tranlist therapy.No significant changes was found for serum creatinine.The side effects were mild,and could be tolerated. Conclusion Tranilast is safe and effect for treating early-stage diabetic nephropathy.

目的 观察基因重组生长激素(recombinant human growth hormone,rhGH)对肾病综合征大鼠血脂水平的影响并探讨其机制.方法 制备阿霉素肾病大鼠模型,设正常对照组(A组,6只)、肾病组(B组,12只)和rhGH治疗组(C组,12只),全自动生化仪测量血清TC、TG、HDL和LDL,以流式细胞仪测量肝细胞GHR的表达,放射免疫法测血清IGF-1水平.结果 (1)B组和C组大鼠TC、TG、LDL明显高于A组(P<0.05),C2组与B2组相比TC、TG、LDL显著降低(P<0.05),C1组HDL水平与B1组相比显著升高(P<0.05).(2)B组和C1组大鼠血清IGF-1浓度显著低于A组,C2组IGF-1水平与A组相比无统计学差异;(3)B组和C组肝脏GHR较A组显著降低(P<0.001),C2组比B2组肝脏GHR表达明显增加(P<0.01).结论 肝细胞GHR表达下降参与了NS大鼠高脂血症的发生,rhGH通过提高肝细胞GHR的表达而调节血脂的水平.

Objective To investigate the effects of recombinant human growth hormone(rhGH)on serum TC,TG,HDL and LDL in nephrotic rats.Methods Thirty male Spraque-Dawley(SD)rats were randomly divided into control group(A group,n=6),doxorubincin-induced nephrotic griyo(B groups,n=12)and rhGH-treated nephrotic group(C groups,n=12).IGF-1 concentration in serum was measured with RIA.TC,TG,HDL and LDL level in serum were measured with automatic biochemistry appliance.GHR level in liver was detected by flow cytometry.Results(1)Serum TC,TG and LDL level of the B and C groups were all significantly higher than those of the A group and these indicators in C2 group were decreasd as compared with B2 group.Serum HDL level was increased significantly in C1 group as compared with B1 group.(2)IGF-1 concentration in serum was decreased in B and C1 groups as compared with A group.No significant difference was observed between C2 group and A group on serum IGF-1.(3)Hepatic GHR expression were significantly decreased in both B and C groups as compared with A group and increased in C2 group compared with B2 group.Conclusion The dyslipidemia in nephrotic rats might be caused by the decreased expression of hepatic GHR.rhGH could improve the serum lipid by promoting the expression of hepatic GHR.

Objective To study the effect of tranilast(Tran) on connective tissue growth factor(CTGF) expression in human renal tubular epithelial cells(HKCs) stimulated with TGF-β1,and explore its antifibrotic mechanism in the tubulointerstitium of the kidney.Methods The cultured HKCs were divided into three groups: ① the control group: cells maintained in DMEM/F12 medium;② the cells treated with TGF-β1(5 ng/ml);and ③ the cells treated with TGF-β1(5 ng/ml) and Tran(100 μmol/L).The immunofluorescence was used to detect the protein expression of phosphorylated Smad2(PSmad2).The reverse transcription polymerase chain reaction(RT-PCR) was performed to evaluate the mRNA expression of CTGF,and Western blot was adopted to assay the protein expression of CTGF and collagen type Ⅵα.Results After TGF-β1 stimulation for 30 min,the protein level of PSmad2 in HKCs' nuclei was markedly enhanced,while significantly decreased in HKCs stimulated with TGF-β1 and Tran(P<0.05).Normal HKCs had no obvious protein expression of PSmad2.Simultaneously,the expression levels of CTGF and collagen type Ⅵ α protein in HKCs stimulated with TGF-β1 were significantly higher than those of control group(both P<0.05),while they were significantly decreased in HKCs stimulated with TGF-β1 and Tran(both P<0.05).Conclusion Tran may be a potential effective antifibrotic compound in the kidney disease by inhibiting TGF-β1-induced CTGF expression,and the inactivation of the Smad2 pathway in HKCs.