抗纤灵二号方对单侧输尿管梗阻大鼠肾小管上皮细胞转分化的调节作用

目的：通过研究中药复方——抗纤灵二号方对单侧输尿管梗阻（unilateral ureteral obstruction,UUO）大鼠肾间质α-平滑肌肌动蛋白（alpha-smooth muscle actin,α-SMA）、转化生长因子-β1（transforming growth factor-beta1,TGF-β1）、肝细胞生长因子（hepatocyte growth factor,HGF）表达的影响,探讨其对肾小管上皮细胞间充质转分化（epithelial mesenchymal transdifferentiation,EMT）的调节机制。方法：建立大鼠UUO模型,90只SD大鼠随机分为假手术组、模型组、代文组,及抗纤灵二号方低、中、高剂量组,于造模4周后腹主动脉采血检测血清肌酐（serum creatinine,Scr）、尿素氮（blood urea nitrogen,BUN）,收集24h尿液检测N-乙酰-β-D-氨基葡萄糖苷酶（N-acetyl-β-D-glucosaminidase,NAG）、β2-微球蛋白（β2-mi-croglobulin,β2-MG）,取梗阻侧肾组织,HE、Masson染色观察肾小管间质病变,免疫组织化学染色观察α-SMA、TGF-β1及HGF在肾间质的阳性染色表达,免疫印迹法检测肾组织α-SMA的蛋白表达,并进行半定量分析。结果：与假手术组相比,模型组大鼠Scr、BUN、尿NAG、β2-MG水平以及α-SMA、TGF-β1阳性表达显著升高（P〈0.01）。与模型组相比,抗纤灵二号方高剂量组大鼠Scr、BUN水平降低,尿NAG、β2-MG排泄减少（P〈0.01）;抗纤灵二号方高剂量组和代文组α-SMA、TGF-β1阳性表达显著下调,而HGF阳性表达则显著上调（P〈0.01）,α-SMA蛋白表达也明显下调（P〈0.05）;低、中、高三个剂量组的疗效呈剂量依赖关系。结论：抗纤灵二号方可能通过改善肾小球、肾小管功能,抑制α-SMA、TGF-β1的表达,诱导HGF的高表达,从而抑制肾小管EMT,达到改善肾间质纤维化的作用。     

Polyenylphosphatidylcholine pretreatment ameliorates ischemic acute renal injury in rats

AIM: Polyenylphosphatidycholine has been demonstrated to have antioxidant, cytoprotective and anti-inflammatory effects. Whether polyenylphosphatidycholine pretreatment affects ischemia/reperfusion-induced renal damage in vivo is not known and was investigated here in rats. METHODS: Forty female Sprague-Dawley rats were divided into three groups. Group 1 (n = 10) was given saline (control, sham operated). Group 2 (n = 15) were given saline, and Group 3 (n = 15) were given polyenylphosphatidycholine (100 mg/day for 10 days prior to experiment). Groups 2 and 3 were subjected to bilateral renal ischemia (60 min) followed by reperfusion (6 h). After the reperfusion period, the rats were sacrificed and kidney tissue superoxide dismutase, glutathione, total nitrite and nitrate, malondialdehyde and myeloperoxidase levels, plasma aspartate aminotransferase, blood urea nitrogen and creatinine concentrations, and nuclear factor kappa beta expression were determined. RESULTS: Serum levels of aspartate aminotransferase, blood urea nitrogen and creatinine were significantly decreased (P < 0.05) in the treatment group compared to those in the ischemic group. There were significant differences between treatment and ischemic groups regarding the tissue superoxide dismutase, glutathione, total nitrite and nitrate, malondialdehyde, and myeloperoxidase levels (P < 0.05). In addition, polyenylphosphatidycholine pretreatment reduced nuclear factor kappa beta expression in ischemic kidney tissue. Kidneys obtained from rats pretreated with polyenylphosphatidycholine demonstrated marked reduction of the histological features of renal injury compared to kidneys obtained from Group 2 rats, including a little vacuolization, pyknosis and necrosis. CONCLUSIONS: Polyenylphosphatidycholine pretreatment provided significant protection against ischemia/reperfusion injury to the kidney. This treatment could be therapeutic in kidney transplantation and other conditions associated with ischemia/reperfusion injury to the kidney.     

TGF-β1及α-SMA在积水肾盂组织中的表达及其相关性研究

目的：检测转化生长因子β1(TGF-β1)和α－平滑肌肌动蛋白（α-SMA）在肾积水肾盂肌层的表达，以探讨TGF－β1对积水肾脏的保护作用。方法：应用免疫组织化学方法对30例积水肾盂和5例正常肾盂标本进行染色观察。结果：积水肾盂标本TGF－β1和α-SMA的表达较正常肾盂标本均增高（P＜0．01），且二者存在显著正相关关系（γ=0.71,P＜0．05）。结论：TGF－β1通过促进肾盂肌层肥厚在肾积水的病理生理过程中发挥保护作用。     

骨形态发生蛋白-7在幼年大鼠肾小管间质损伤中的表达及意义

目的：探讨单侧输尿管梗阻（UUO）幼年大鼠肾间质纤维化形成过程中骨形态发生蛋白-7（BMP-7）的表达趋势及其与转化生长因子-β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）的相关关系;观察血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体拮抗剂（ARB）的干预作用。方法：采用单侧输尿管结扎制备UUO模型。3～4周龄幼年Wistar雄性大鼠随机分为对照组、模型组和干预组。于实验第3、7、14、28天取大鼠8只处死。HE及Masson染色观察肾组织的病理改变;免疫组化半定量检测各组大鼠肾组织BMP-7、TGF-β1及α-SMA蛋白表达。了解BMP-7与TGF-β1、α-SMA、肾间质纤维化程度的关系。结果：随梗阻时间延长,模型组BMP-7表达逐渐下降,TGF-β1、α-SMA表达进行性增高,干预组BMP-7表达较模型组显著增加（P〈0.05）;TGF-β1、α-SMA表达较模型组明显减少（P〈0.05）。模型组肾小管间质TGF-β1、α-SMA表达明显增高（P〈0.05）,BMP-7表达显著减少（P〈0.05）。与模型组相比,干预组肾小管间质TGF-β1、α-SMA表达显著减少（P〈0.05）,而BMP-7表达显著增多（P〈0.05）。BMP-7与TGF-β1、α-SMA、肾间质纤维化程度成负相关（r分别为-0.844、-0.787、-0.952,P均〈0.01）。结论：BMP-7表达减少伴随着肾小管上皮细胞转分化出现,提示BMP-7可能具有维持小管上皮细胞表型作用。苯那普利联合氯沙坦可能通过下调TGF-β1、α-SMA蛋白的异常高表达,上调BMP-7蛋白的异常低表达,直接或间接负性调控肾小管上皮细胞转分化,阻止肾间质纤维化进展。     

Erythropoietin and its non‐erythropoietic derivative: Do they ameliorate renal tubulointerstitial injury in ureteral obstruction?

Objectives: Pleiotropic effects of recombinant human erythropoietin (EPO) have recently been discovered in many non‐renal animal models. The renoprotective effects of EPO and carbamylated‐erythropoietin (CEPO), a novel EPO which has a small stimulatory effect on hemoglobin, have never been explored in unilateral ureteral obstruction (UUO), a chronic tubulointerstitial (TI) disease model which is independent of systemic factors. Methods: In order to examine the effects of EPO and CEPO treatments on renal TI injury, 36 male Sprague‐Dawley rats, weighing 250–320 g, underwent: UUO without treatment (group 1, n = 12), UUO with EPO (groups 2, n = 12), and UUO with CEPO (group 3, n = 12). EPO and CEPO were injected subcutaneously at a dose of 5000 u/kg to each respective rat at 1 day pre‐UUO and at day 3, 7 and 10 post‐UUO. After days 3, 7, and 14 of UUO, TI injury, collagen, α‐smooth muscle actin (α‐SMA) positive cell, ED1‐positive cell, terminal deoxynucleotidyl transferase (TdT) mediated nick‐end labeling (TUNEL)‐positive cell, and transforming growth factor‐β1 (TGF‐β1) messenger ribonucleic acid (mRNA) were determined. Bcl‐2 expression was also assessed to verify the mechanism of apoptosis. Results: At day 14 UUO caused severe TI injury with a significant increase in collagen, α‐SMA, ED1‐positive cell, TUNEL‐positive cell, and TGF‐β1 mRNA expression. Administration of EPO and CEPO significantly attenuated TI injury, collagen, ED1‐positive cells, and TUNEL‐positive cells. Only CEPO‐treated rats had decreased α‐SMA positive cells and TGF‐β1 mRNA. The expression of Bcl‐2 was demonstrated only in EPO‐treated rats. The hematocrit levels in EPO‐treated rats were higher than the control and CEPO‐treated rats. Conclusions: EPO and CEPO can limit 14‐day UUO‐induced TI injury by reducing inflammation, interstitial fibrosis, and tubular apoptosis.     

小鼠单侧输尿管梗阻诱导肾脏纤维化模型中Cadherin6的表达变化

目的研究钙黏蛋白6(cadherin6,CDH6)在肾脏纤维化中表达的变化。方法建立单侧输尿管梗阻(UUO)小鼠模型,术后21天收获肾脏组织,HE染色观察肾间质纤维化程度,RT-q PCR检测肾组织FSP-1、TGF-β1、CDH6 m RNA表达量,免疫组化染色检测肾组织FSP-1、CDH6蛋白表达量;TGF-β1刺激人肾小管上皮细胞HK-2,RT-q PCR及Western Blot分别检测FN1、PAI-1、CDH6 m RNA表达量及CDH6蛋白表达量。结果 HE染色显示UUO组小鼠肾脏出现肾小管萎缩、大量基质沉积,与Sham组相比,UUO组小鼠肾脏组织FSP-1、TGF-β1、CDH6 m RNA表达量及FSP-1、CDH6蛋白表达量均上调;细胞实验结果显示,与空白对照组相比,TGF-β1诱导的HK-2细胞形态向成纤维细胞转变,FN1、PAI-1m RNA表达水平上调,CDH6 m RNA及蛋白表达水平上调。结论 TGF-β1诱导的肾小管上皮细胞CDH6及纤维化相关因子表达上调,伴随上皮细胞向间质表型转化,可能参与单侧输尿管梗阻诱导的小鼠肾脏纤维化的发展。     

单侧输尿管梗阻对对侧肾小管上皮细胞凋亡影响的研究

目的探讨单侧输尿管梗阻对对侧肾小管上皮细胞凋亡的影响。方法新西兰大白兔48只,随机建立右侧输尿管完全梗阻4周和8周组;部分梗阻4周和8周组;假手术4周和8周组动物模型,每组8只。分别于梗阻4周、8周时取对侧肾脏,称重后利用TUNEL法检测对侧肾小管上皮细胞凋亡,并行HE染色。结果梗阻4周、8周均引起对侧肾实质代偿性增生,与梗阻程度及时间正相关（P〈0.05）。梗阻4周组HE染色见少数肾小管扩张,腔内存在坏死脱落细胞,以完全梗阻明显,但8周较4周相应各组无明显变化。TUNEL法检测完全梗阻、部分梗阻及假手术4周组对侧近曲小管上皮细胞凋亡指数分别为（6.02±1.21）%、（3.87±1.70）%、（2.32±1.39）%;远曲小管上皮细胞凋亡指数分别为（12.08±2.33）%、（7.22±3.35）%、（3.38±2.34）%;8周组对侧近曲小管上皮细胞凋亡指数分别为（7.00±2.19）%、（4.47±2.11）%、（2.29±0.85）%;远曲小管上皮细胞凋亡指数分别为（13.02±3.16）%、（8.11±2.99）%、（3.63±1.96）%。相应各组组间比较均有统计学意义（P〈0.05）,但8周与4周相应各组比较均无统计学意义（P〉0.05）。结论单侧输尿管梗阻早期可引起对侧肾小管上皮细胞损害,但随梗阻时间的延长并未进一步加重。     

Resveratrol as a therapeutic agent for renal fibrosis induced by unilateral ureteral obstruction

Aims: Renal fibrosis is a common outcome of chronic kidney disease. This study was designed to examine the protective effects of resveratrol (RSV) against renal fibrosis induced by unilateral ureteral obstruction (UUO). We also attempted to elucidate the potential mechanism involved. Methods: Mice were randomly divided into three groups: sham-operated, UUO, and UUO/RSV (20?mg·kg^?1·day^?1). Histological changes were examined using periodic acid-Schiff and Masson’s trichrome staining after 14 days. Superoxide dismutase (SOD), malondialdehyde (MDA), and 8-OHdG levels were determined using a commercially available kit. ICAM-1, TNF-α, and TGF-β levels were measured using real-time PCR. Fibronectin levels were measured by western blot, and the Smad3 acetylation and Sirt1 were examined by immunoprecipitation and western blot. Results: Our study showed that RSV treatment significantly attenuated renal injury including extracellular matrix deposition and tubulointerstitium damage. Renal cortical mRNA levels of ICAM-1, TNF-α, and TGF-β, protein expression of fibronectin and Smad3 acetylation were significantly upregulated in the UUO group. However, treatment with RSV significantly decreased the expression of these proteins. Furthermore, RSV also decreased the levels of reactive oxygen species (ROS) including MDA and 8-OHdG, and increased the level of SOD, which protects cells against ROS damage. Conclusion: Our findings suggest that RSV treatment inhibits oxidative stress, Smad3 acetylation, and renal interstitial fibrosis. Therefore, RSV may have potential as a therapeutic target for the treatment of chronic kidney disease.     

Effects of proteasome inhibitors on rat renal fibrosis in vitro and in vivo

Aim: Transforming growth factor‐β (TGF‐β) is involved in renal tubulointerstitial fibrosis. Recently, the ubiquitin proteasome system was shown to participate in the TGF‐β signalling pathway. The aim of this study was to examine the effects of proteasome inhibitors on TGF‐β‐induced transformation of renal fibroblasts and tubular epithelial cells in vitro and on unilateral ureteral obstruction (UUO) in vivo. Methods: Rat renal fibroblasts NRK‐49F cells and tubular epithelial cells, NRK‐52E, were treated with TGF‐β in the presence or absence of a proteasome inhibitor, MG132 or lactacystin. Rats were subjected to UUO and received MG132 i.p. for 7 days. Results: In cultured renal cells, both MG132 and lactacystin inhibited TGF‐β‐induced α‐smooth muscle actin (α‐SMA) protein expression according to both western blotting and immunofluorescent study results. MG132 also suppressed TGF‐β‐induced mRNA expression of α‐SMA and upregulation of Smad‐response element reporter activity. However, MG132 did not inhibit TGF‐β‐induced phosphorylation and nuclear translocation of Smad2. In contrast, MG132 increased the protein level of Smad co‐repressor SnoN, demonstrating that SnoN is one of the target molecules by which MG132 blocks the TGF‐β signalling pathway. Although the proteasome inhibitor suppressed TGF‐β‐induced transformation of cultured fibroblasts and tubular epithelial cells, MG132 treatment did not ameliorate tubulointerstitial fibrosis in the rat UUO model. Conclusion: Proteasome inhibitors attenuate TGF‐β signalling by blocking Smad signal transduction in vitro, but do not inhibit renal interstitial fibrosis in vivo.     

Effects of renal sympathetic denervation on renal interstitial fibrosis in rats with unilateral ureteral obstruction

Objective To observe the influence of renal sympathetic denervation (RSD) on renal interstitial fibrosis and transforming growth factor beta 1(TGF-β1) and microRNA-21 (miR-21) in rats with unilateral ureteral obstruction(UUO). Methods 40 male Wistar rats were randomly divided into UUO group (A group, n=10), sham UUO group (B group, n=10), RSD+UUO group (C group, n=10) and RSD+sham UUO group (D group, n=10). Rats in A group and C group underwent unilateral ureteral ligation, while those in B group and D group underwent sham operation. Rats in C group and D group were followed by RSD. Rats were sacrificed at 21 days after the operation to evaluate the fibrosis by Masson staining. Immunohistochemical staining and Western blotting were used to detect the expressions of collagen I (COL-I), collagen Ⅲ(COL-Ⅲ) and TGF-β1 in four groups. The expression of miR-21 was detected by fluorescence in situ hybridization (FISH) and quantitative real-time PCR (RT-qPCR). Results A large amount of collagen deposition was observed in the renal interstitial area in A and C group compared to either B or D group (P＜0.05), but the change in C group was decreased significantly than that in A group (P＜0.05). Similarly, the expressions of COL-I, COL-Ⅲ, TGF-β1 and miR-21 were obviously higher in A and C group compared to either B or D group (P＜0.05), but those change in C group were decreased significantly than those in A group (P＜0.05). The above indexes were not significantly different between B group and D group (P＞0.05). Conclusion RSD may relieve the renal interstitial fibrosis in UUO rats, and down-regulate the expression of TGF-β1 and miR-21.     

依那普利对梗阻性肾病大鼠肾组织p38丝裂素激活蛋白激酶活性的影响

目的研究血管紧张素转换酶抑制剂(ACEI)依那普利对梗阻性肾病模型肾组织p38丝裂素激活蛋白激酶(MAPK)活性的影响。方法采用单侧输尿管结扎(UUO)模型,治疗组从造模前24h至造模后28d以依那普利10mg·kg-1·d-1灌胃,另设假手术组作正常对照。分别于造模后1h,3h,6h,12h,1d,3d,5d,7d,14d,21d及28d取肾组织,应用免疫沉淀结合特异性底物磷酸化法测定肾组织p38MAPK活性;免疫组织化学法检测磷酸化p38MAPK在肾组织中的表达和定位;免疫组织化学及原位杂交方法检测肾组织TGF-β1mRNA和蛋白水平的表达。结果正常大鼠肾组织基础的p38MAPK活性(吸光度值)为0.22±0.06。UUO术后1h,p38MAPK即被激活(0.45±0.14,P<0.01),并呈进行性升高,12h时达第1个高峰(0.91±0.07,P<0.01),此后活性逐渐下降;第3天后又进行性升高,第7天达到第2个高峰(0.93±0.06,P<0.01)。TGF-β1的表达在UUO术后1h、3h、6h、12h及24h均无明显增加;在第3天有明显增加(A值,13.55±6.33比基础4.32±1.72,P<0.01);第7天达高峰(26.78±8.77,P<0.01)。梗阻肾肾组织p38MAPK的激活明显早于TGF-β1表达,且p38MAPK早期活性的强弱与肾组织TGF-β1的表达水平相一致。依那普利治疗可以明显抑制p38MAPK活性(下降36%～65%,P<0.01),显著降低肾组织TGF-β1表达(下降33%～4     

补体C5α受体和转化生长因子-β1在大鼠肾间质纤维化不同阶段肾组织的表达

目的：动态观测补体C5α受体（C5αR）和转化生长因子β1（TGF-β1）在单侧输尿管梗阻（UUO）大鼠肾组织的表达变化,从而探讨C5αR在。肾小管间质纤维化发生中的作用机制。方法：将36只雄性SPF级SD大鼠随机分为模型组及假手术组。模型组行UUO术,假手术组仅游离输尿管,不结扎。术后第5、10、15天分别处死每组中的6只大鼠,取梗阻侧肾行苏木精-伊红（H—E）和Masson染色,并用免疫组织化学ELiVision^TMplus法检测肾小管间质中C5αR和TGF-β1的表达。结果：模型组第5天肾小管扩张,小管间质细胞部分变性,第10天小管间质细胞可见坏死,间质纤维增多,第15天可见弥漫的肾小管基底膜增厚皱缩,纤维化明显（P〈0．05）。免疫组织化学结果显示：假手术组大鼠肾小管间质中仅有少量TGF-β1和C5αR表达,随时间延长未见明显变化;模型组大鼠梗阻侧肾组织中C5αR和TGF-β1的表达随时间进展而明显增加（P〈0．05）,其中C5αR在梗阻早期（第5～10天）表达明显增多,而晚期（第11～15天）仅轻微增多。结论：模型组实验大鼠梗阻侧。肾组织中C5αR和TGF-β1表达随着梗阻时间延长而上调,提示C5αR可能在。肾间质纤维化早期通过介导TGF-β1的上调发挥作用。     

TGF-β和α-SMA在瘢痕组织中的表达及相关性研究

目的 检测转化生长因子－β（ＴＧＦ－β１,ＴＧＦ－β２,ＴＧＦ－β３）在增生性瘢痕和表浅性瘢痕中的表达,探讨其对增生性瘢痕的形成及α－平滑肌肌动蛋白（α－ＳＭＡ表达的可能作用。方法 采用免疫组化法检测２８例增生性瘢痕,１９例表浅性瘢痕和１６例正常皮肤组织中ＴＧＦ－β和α－ＳＭＡ的表达水平,并按年龄,性别,病程分组进行比较及ＴＧＦ－β和α－ＳＭＡ相关性分析。     

金属蛋白酶组织抑制剂1在大鼠肾小管间质损害中的表达及其意义

目的 观察单侧输尿管梗阻(UUO)大鼠模型中金属蛋白酶组织抑制剂1(TIMP-1)在肾小管间质中的表达部位、动态变化及其与肾小管问质损害的关系。方法 制备UUO大鼠模型,采用免疫组织化学方法检测UUO术后第1、3、5、7、14天肾小管间质中TIMP-1、α-平滑肌肌动蛋白(SMA)、增殖细胞核抗原(PCNA)和单核巨噬细胞抗原(ED)-1的表达及其与输尿管梗阻后肾小管间质损害的关系。结果 UUO术后第1天肾间质可见少量TIMP-1表达细胞,第3～7天TIMP-1表达明显增加,主要表达于肾小管上皮细胞和肾间质。UUO术后第3天肾小管PCNA表达达高峰,随后下降,而肾间质PCNA水平于第7～14天仍较高。UUO术后第3天肾间质成纤维细胞及肾小管上皮细胞可检出α-SMA表达并随时间递增。α-SMA阳性面积与肾间质相对面积成正相关(r=0.924,p<0.01)。TIMP-1表达与间质相对面积(r=0.835,P<0.05)及α-SMA阳性面积(r=0.922,P<0.01)成正相关。结论 TIMP-1蛋白质于肾小管间质病变早期表达于肾小管间质,早于肾间质纤维化出现,其表达量与肾间质α-SMA表达及肾间质相对面积呈正相关并随病变进展逐渐增加。TIMP-1在肾小管上皮细胞和问质细胞的高表达及肾小管上皮细胞和间质细胞增殖可能参与介导UUO术后肾小管间质损害。     

intermedin对单侧输尿管梗阻大鼠肾间质纤维化的影响

目的 观察intermedin( IMD)对单侧输尿管梗阻(UUO)大鼠肾间质纤维化的影响.方法 雄性Wistar大鼠40只,按随机数字表法分为假手术组(n=10,行左输尿管分离术)、模型组(UUO,n=10)、氯沙坦组(n=10)和IMD组(n=10),后3组行左输尿管结扎术.各组大鼠分别于术后第14、21天随机选取5只,腹主动脉采血并留取梗阻侧肾组织之后处死.HE、Masson染色观察肾组织病理变化;比色法测定血尿素氮(BUN)、血肌酐(Scr)及新鲜肾组织羟脯氨酸(Pro)含量;免疫组化方法检测肾组织中转化生长因子β1 (TGF-β1)、IMD的表达水平,并进行半定量分析.结果 与假手术组相比,不同时间点UUO组血BUN、Scr、肾组织Pro含量及TGF-β1、IMD的阳性表达均显著升高(P＜0.05);与UUO组相比,氯沙坦组血BUN、Scr、肾组织Pro含量及TGF-β1、IMD表达均降低(P＜0.05),IMD组除IMD表达增加外,其余均降低(P＜0.05).结论 IMD可减轻UUO肾间质纤维化,改善肾功能,其机制可能与拮抗纤维化炎性介质TGF-β1有关.     

Curcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction

In this study, we explored the role and mechanism of repulsive guidance molecule B (RGMb, also known as Dragon) in the protective effects of curcumin against renal fibrosis and verified Dragon’s effect on renal tubular epithelial cell apoptosis and cell programmability. Unilateral ureteral obstruction (UUO) was surgically induced in rats to establish a model of renal interstitial fibrosis (RIF). The rats were then treated with curcumin. Curcumin prominently decreased the serum creatinine (SCr) and blood urea nitrogen (BUN) levels, and also improved the tubular injury in the UUO-induced rats. Curcumin significantly downregulated the TGF-β1, P-Smad2/3, cleaved caspase-3, cleaved caspase-8 and Dragon levels. Dragon knockdown also markedly reduced the TGF-β1, P-Smad2/3, Smad2/3, cleaved caspase-3, cleaved caspase-8, fibronectin, collagen I, collagen IV, vimentin, and α-SMA expression levels. Conversely, Dragon overexpression caused higher expression levels of these proteins, and curcumin reversed this effect. Furthermore, Dragon knockdown increased the E-cadherin levels, whereas Dragon overexpression decreased these levels. Overexpressing Dragon significantly decreased the cell viability, and curcumin reversed this effect. In conclusion, curcumin acted on Dragon and attenuated RIF in UUO rat models. Curcumin downregulated the TGF-β1/Smad signaling pathway and inhibited Dragon and fibrogenic molecules in both rats and HK-2 cells.     

人脂肪干细胞向血管平滑肌细胞诱导分化的实验研究

目的：体外诱导培养人脂肪干细胞（adi pose-der i ved st em cel l s,ADSCs）,观察是否可以分化形成血管平滑肌细胞（vascul ar smoot h muscl e cel l s,VSMCs）,为构建组织工程化血管寻找新的种子细胞来源。方法：免疫磁珠法分选收集原代脂肪干细胞,加入PDGF-BB、TGF-β1诱导14天后进行检测。结果：实验组细胞生长呈现血管平滑肌细胞所特有的峰谷样生长,血管平滑肌细胞特有的表面抗原标记物表达阳性。结论：脂肪干细胞定向诱导培养后,具有血管平滑肌细胞的特性,有可能成为构建组织工程化血管新的种子细胞来源。