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1.
目的探讨α-酮戊二酸钠对转化生长因子β1(TGF-β1)诱导的HK-2细胞上皮-间充质转分化(EMT)的影响。方法 TGF-β10.5,2和5μg.L-1分别作用于葡萄糖5和30 mmol.L-1培养的HK-2细胞72 h,通过RT-PCR法检测EMT标志物E-钙黏着糖蛋白和波形蛋白mRNA表达的变化,以选择EMT病变模型的最佳诱导条件。在此基础上,观察α-酮戊二酸钠10,100和500μmol.L-1对HK-2细胞EMT病变及G蛋白偶联受体80(GPR80)mRNA表达的影响。结果①在葡萄糖5和30 mmol.L-1条件下,当TGF-β1为5μg.L-1时,与对照组比较,E-钙黏着糖蛋白mRNA的降低和波形蛋白mRNA的升高最明显(P<0.01),表明HK-2细胞发生了典型的EMT病变;②选择TGF-β15μg.L-1和葡萄糖30 mmol.L-1制备EMT病变模型,同时加入α-酮戊二酸钠100和500μmol.L-1作用72 h,与模型组比较,E-钙黏着糖蛋白mRNA明显升高,波形蛋白mRNA明显降低,GPR80 mRNA表达增加(P<0.01),表明α-酮戊二酸钠可逆转HK-2细胞EMT的发生。结论在葡萄糖5和30 mmol.L-1培养条件下,TGF-β15μg.L-1作用72 h,HK-2细胞可出现典型的EMT病变;α-酮戊二酸钠对该病变具有抑制作用。  相似文献   

2.
目的观察百令胶囊对肾小管间质纤维化大鼠肾脏α-平滑肌肌动蛋白(α-smooth muscleactin,α-SMA)表达的影响,探讨百令胶囊肾脏保护作用的可能机制。方法雄性3个月龄SD大鼠90只,随机分为:对照组(30只),模型组(30只),预防组(30只),以腺嘌呤灌胃法建立大鼠肾小管间质纤维化模型,预防组加以1.5 g/(kg.d)百令胶囊溶于生理盐水灌胃以预防肾小管间质纤维化;对照组以等体积的2%淀粉溶液和生理盐水灌胃。分别于实验第7、12、17周时随机处死10只大鼠,进行血肌酐(creatinine,Cr)、尿素氮(blood urea nitrogen BUN),24 h尿蛋白定量和尿N乙-酰-β-D氨-基葡萄糖苷(N-a-cetylβ--D-glucosam inidase,NAG)酶检测,光镜下观察肾组织的病理变化及免疫组织化学法检测肾脏转化生长因子-β1(transform ing growth factor-beta1,TGFβ-1)、α-SMA的表达情况。结果①功能学变化:与对照组比较,各时相点模型组、预防组大鼠尿蛋白、尿NAG酶、血Cr及血BUN均升高(P〈0.01),但预防组低于模型组(P〈0.01);模型组、预防组自身对照各指标均较前一时相点升高(P〈0.01)。②病理学变化:7周时模型组、预防组即有肾小管间质损害;模型组、预防组自身对照肾小管间质损害均较前一时相点加重(P〈0.01),但7、12周时预防组肾小管间质损害均较模型组为轻(P〈0.01),17周时两组间差异无统计学意义(P=0.670)。③免疫组化:各时相点模型组、预防组大鼠肾脏TGFβ-1、α-SMA的表达均高于对照组(P〈0.01),但预防组均低于模型组(P〈0.01),模型组、预防组自身对照均较前一时相点升高(P〈0.01),17周时表达量最高。结论百令胶囊可能通过抑制α-SMA,在肾小管间质纤维化早期应用时起到保护作用。  相似文献   

3.
陈幼发  熊羽 《重庆医药》2009,38(15):1902-1904,1907
目的探讨全反式维甲酸对糖尿病大鼠肾小管一阀质纤维化的作用以及对肾问质转化生长因子β1(TGF-β1)、α平滑肌肌动蛋白(α—SMA)表达的影响。方法24只链脲佐菌素(STZ)诱导的糖尿病大鼠模型,随机分为治疗组(T)、模型组(D)各12只、正常组12只(N),T组给予全反式维甲酸(atRA)(20mg&#183;kg^-1&#183;d^-1)油溶液灌胃,D组和N组分别灌等量的植物油。4、8周每组各处死大鼠6只,测量24h尿微量清蛋白排泄率、肾重/体质量、血肌酐、血糖(BS)。肾组织PAS、Masson染色。免疫组化方法检测肾小管间质TGF-β1、α—SMA的表达。结果atRA可减轻肾小球系膜区基质、细胞的增生,明显缓解肾小管一间质的纤维化。4周尿清蛋白的排泄率实验组低于模型组[(3.08&#177;0.48)μg/min与(3.35&#177;o.56)μg/min,P〈0.05),8周时尿清蛋白的排泄率明显低于同期模型组[(2.49&#177;0.40)μg/min与(4.53&#177;0.87)μg/min,P〈0.01];肾小管上皮细胞TGF—β1的表达明显低于模型组(P〈0.01),肾小管间质α-SMA的表达明显低于模型组(P〈0.01)。结论atRA可减轻糖尿病大鼠肾小管一间质的纤维化,减少尿蛋白。可能通过下调肾小管一间质TGF-β1的表达、减少肾小管一间质肌成纤维细胞的数量,防止肾间质的纤维化,保护肾功能。  相似文献   

4.
目的:观察人参皂甙Rg1对转化生长因子-β1诱导的肾小管上皮细胞增殖及细胞外基质的影响.方法:MTT法测细胞增殖情况.ELISA法测定培养细胞上清液中Col-Ⅰ,Col-Ⅲ和FN的含量.结果:在10~40 ng/mL浓度范围内时间、剂量依赖性的促进肾小管上皮细胞增殖,减少转化生长因子-β1诱导的肾小管上皮细胞对Col-Ⅰ、Col-Ⅲ、FN的分泌.结论:G-Rg1能够促进TGF-β1诱导下的肾小管上皮细胞的增殖,可能与抑制ECM的分泌有关.  相似文献   

5.
目的探讨丹参注射液对单侧输尿管梗阻(UUO)大鼠肾间质纤维化的影响。方法采用UUO致肾间质纤维化大鼠模型。24只雄性Wistar大鼠,随机分为假手术组、模型组和丹参组。术后第10天取术侧肾组织做HE,Masson染色及转化生长因子(TGF)β-1,α-平滑肌肌动蛋白(α-SMA)免疫组织化学检测。结果丹参组显著改善梗阻侧肾组织病理变化,下调TGFβ-1和α-SMA蛋白表达。结论丹参注射液对梗阻性大鼠肾间质纤维化有保护作用。  相似文献   

6.
目的 研究转化生长因子-β(TGF-β)通路的激活与阻断对人胃癌HGC-27细胞增殖、侵袭及slug蛋白和上皮钙黏素(E-cadherin,E-cad)表达的影响。方法 于2021年1月至2022年1月使用外源性通路激活剂TGF-β1和阻断剂SB431542培养胃癌细胞,后根据对细胞给药不同分为五组。空白对照组:仅使用等量常规培养基;激动剂组:TGF-β1(25μg/L);阻断剂组:SB431542(2 mg/L);激动剂+低浓度阻断剂组:TGF-β1(25μg/L)+SB431542(2 mg/L);激动剂+高浓度阻断剂组:TGF-β1(25μg/L)+SB431542(4 mg/L)。并使用细胞计数试剂盒(CCK-8)法检测各组胃癌细胞增殖活性,使用Transwell侵袭实验检测各组胃癌细胞侵袭能力,使用酶联免疫吸附测定(ELISA)检测胃癌细胞中slug与E-cad两种蛋白的表达情况。结果 五组胃癌细胞增殖活性、侵袭能力及slug蛋白、E-cad蛋白表达水平比较均差异有统计学意义(P<0.05)。激动剂组胃癌细胞增殖活性(24 h:0.70±0.13)和侵袭能力[细胞穿过小...  相似文献   

7.
吴欣  李聃丹  蒋文勇  刘畅  于黔 《江苏医药》2012,38(15):1743-1746,1861
目的研究1,25-二羟维生素D3对糖尿病肾病大鼠肾小管上皮细胞转分化的影响及其可能机制。方法 28只SD大鼠随机分为正常对照组(N组,8只)、糖尿病肾病模型组(M组,10只)、1,25-二羟维生素D3干预组(D组,10只)。检测各组大鼠24-h尿蛋白(24-h Upro)、血尿素氮(BUN)、血清肌酐(SCr)水平,HE染色观察肾组织病理学变化,应用免疫组化、RT-PCR方法分别检测大鼠肾组织α-平滑肌肌动蛋白(α-SMA)和上皮细胞钙黏素(E-cad)的蛋白及其mRNA的表达。结果与N组相比,M组大鼠肾小管间质损伤加重,24-h Upro及SCr水平、α-SMA蛋白及mRNA表达增加,E-cad蛋白和mRNA表达减少(P<0.05);而D组能明显逆转M组上述各观察指标的改变过程(P<0.05)。结论 1,25-二羟维生素D3可能通过下调糖尿病肾病大鼠肾组织α-SMA表达,上调E-cad表达,从而抑制肾小管上皮细胞转分化,减轻肾小管间质病理损伤而发挥其肾脏保护作用。  相似文献   

8.
目的 探讨重组人肝细胞生长因子(rhHGF)对结缔组织生长因子(CTGF)刺激下肾小管上皮间质纤维化的影响.方法 体外培养人肾小管上皮细胞(HKC),在CTGF培养的HKC中加入不同浓度rhHGF分别刺激96 h,提取细胞总RNA,运用RT-PCR技术检测纤维化指标IV型胶原(COL4A1)、纤连蛋白(FN)、α平滑肌肌动蛋白(α-SMA)等的基因表达;并以Western印迹法检测α-SMA的蛋白表达改变.结果 rhCTGF加rhHGF组纤维化指标FN和α-SMA表达均较rhCTGF组明显下降(P< 0.01).结论 HGF可抑制CTGF所致HKC间质纤维化.  相似文献   

9.
目的观察人参皂苷Rg1(G-Rg1)对单侧输尿管梗阻(UUO)模型大鼠肾组织内质网应激反应(ERS)的影响。方法 22只SD大鼠随机分为假手术组、模型组、治疗组。治疗组在UUO的基础上给予G-Rg120 mg·kg-1·d-1腹腔注射,模型组及对照组均给予等剂量的生理盐水腹腔注射。14 d后处死大鼠,收集血标本检测肾功能,肾组织行肾脏病理染色及蛋白印迹法检测各组大鼠内质网应激相关蛋白GRP78、凋亡蛋白CHOP等的表达情况。结果模型组大鼠肾功能恶化明显,肾间质纤维化、炎细胞浸润等明显加重;蛋白印迹法结果表明GRP78、CHOP的表达明显增多;治疗组大鼠肾功能明显好转,肾脏病理损害减轻,同时ERS相关蛋白GRP78、CHOP的表达下降。结论 G-Rg1可以通过抑制内质网应激反应减轻UUO模型的肾间质纤维化,发挥肾脏保护作用。  相似文献   

10.
目的:用转化生长因子(TGF-β1)诱导人肾小管上皮细胞(HK-2)转分化,观察丹酚酸B(SA-B)对HK-2细胞转分化过程的干预作用并初步探讨其机制。方法:TGF-β1(5 ng.mL-1)刺激HK-2细胞,用丹酚酸B(SA-B)(10μmol.L-1)干预;用免疫荧光法检测各组HK-2细胞黏着斑激酶(FAK)、整合素β1(β1-integrin)的表达。结果:TGF-β1成功诱导HK-2转分化;相比空白对照组,SA-B可抑制HK-2转分化,且SA-B可有效降低HK-2细胞FAK及β1-integrin蛋白的表达(P均小于0.05)。结论:SA-B可有效调节人肾小管上皮细胞转分化过程,其机制可能与其能调控HK-2细胞FAK及β1-integrin蛋白的表达有关。  相似文献   

11.
目的探讨缬沙坦(Valsartan,Val)对单侧输尿管结扎(unilate ral ureteral obstruction,UUO)大鼠肾间质纤维化的影响及其药学作用机制。方法 18只SD大鼠制作UUO模型后随机分为3组,缬沙坦组给予缬沙坦灌胃治疗,假手术组、模型组给予生理盐水灌胃治疗。4周后腹主动脉采血,检测血浆血管紧张素Ⅱ(angiotensinⅡ,AngⅡ),取UUO侧肾组织,行Masson染色观察肾小管间质病变,免疫组织化学染色观察a-平滑肌肌动蛋白(alpha-smooth muscle actin,a-SMA)和转化生长因子-β1(transforming growth factor-beta 1,TGFβ-1)在肾小管间质的表达,并运用图像分析系统进行半定量分析。结果缬沙坦可以显著减少血浆AngⅡ的含量(P〈0.01),下调a-SMA和TGFβ-1的表达(P〈0.01),减轻肾间质纤维化的程度(P〈0.01)。结论缬沙坦可能通过阻断AngⅡ的生成,抑制TGF-β1、a-SMA的表达,从而达到抑制肾纤维化的作用。  相似文献   

12.
AIM: To examine whether the reversibility of chronic cyclosporine A (CsA) nephrotoxicity is associated with apoptotic cell death and its regulatory factors. METHODS: Chronic CsA nephrotoxicity was induced in Sprague- Dawley rats by administering CsA (15 mg/kg, sc) for 5 weeks, and then withdrawing it for 5 or 10 weeks. The effect of CsA withdrawal on apoptotic cell death was evaluated by an in situ TdT-mediated deoxyuridine triphos- phate-biotin nick end-labeling (TUNEL) assay a…  相似文献   

13.
14.
目的观察螺内酯能否阻抑百草枯(PQ)中毒大鼠肺纤维化及探讨其可能的作用机制。方法54只雄性SD大鼠随机分为对照组、PQ染毒组(一次性PQ80mg/kg灌胃)和螺内酯干预组(一次性PQ80mg/kg灌胃并予每天1次螺内酯100mg/kg灌胃)。各组大鼠于染毒后第7、14、28天分批处死,取肺组织行HE染色、Masson染色并做肺泡炎、肺纤维化评分,计算肺系数,测血浆及肺组织醛固酮(ALD)含量及肺羟脯氨酸含量,应用免疫组化法测肺组织转化生长因子-β1(TGF-β1)及α-平滑肌肌动蛋白(α—SMA)蛋白的表达。结果染毒组和干预组血浆、肺组织ALD含量均较对照组升高,第14天始差异有统计学意义(P〈0.05);干预组各时间点大鼠肺泡炎和肺纤维化程度积分、肺系数、肺羟脯氨酸含量均低于染毒组(P〈0.01);干预组第14天始肺组织TGF—β1、α-SMA蛋白的表达均低于染毒组(P〈0.05或P〈0.01)。结论ALD、TGFβ1、α—SMA可能均参与PQ中毒致肺纤维化的发病进程。螺内酯对PQ中毒大鼠肺纤维化有一定程度的阻抑作用,可能与其抑制ALD受体,并减少肺部TGF-β1和aSMA的表达有关。  相似文献   

15.
李素方  顾民  刘敏  吴宏飞  徐正铨  眭元庚  张炜 《江苏医药》2007,33(10):1025-1027
目的 观察16,16二甲基前列腺素E2(dmPGE2)对大鼠环孢素A(CsA)肾毒性防治作用.方法 以40 mg·kg-1·d-1的CsA剂量灌胃制成大鼠环孢素A肾毒模型,同时以10 μg·kg-1·d-1的dmPGE2皮下注射,分别于治疗1、2、4周检测相关指标.结果 实验成功复制大鼠CsA肾毒模型.dmPGE2能明显改善CsA肾中毒大鼠的肾小管损害,降低尿N-乙酰-β-氨基葡萄糖苷酶(NAG)生成,亦能防止CsA用药后引起的血清肌酐的升高.大鼠肾组织病理证实,dmPGE2能减少肾小管上皮细胞的空泡变性和坏死,减轻肾小球囊毛细血管闭锁,减轻入球动脉的透明样变性.结论 dmPGE2能有效防治大鼠CsA肾毒性.  相似文献   

16.
Cyclosporine is an important immunosuppressive agent; however, nephrotoxicity is one of the main adverse effects. The purpose of this study was to evaluate the effect of inhibiting the protein kinase A (PKA) signaling pathway in nephrotoxicity caused by cyclosporine from the assessment of cell viability, pro-inflammatory cytokines, and nitric oxide (NO) production in LLC-PK1 and MDCK cell lines. Cyclosporine proved to be cytotoxic for both cell lines, as assessed by the mitochondrial enzyme activity assay (MTT), caused DNA fragmentation, determined by flow cytometry using the propidium iodide dye, and activated the PKA pathway (western blot assay). In MDCK cells, the inhibition of the PKA signaling pathway (H89 inhibitor) caused a significant reduction in DNA fragmentation. In both cell lines, the production of IL-6 proved to be a dependent PKA pathway, while TNF-α was not influenced by the inhibition of the PKA pathway. The NO production was increased when cells were pre-incubated with H89 followed by cyclosporine, and this production was dependent on the PKA pathway in LLC-PK1 and MDCK cells lines. Therefore, considering the present study's results, it can be concluded that the inhibition of PKA signaling pathway can aid in reducing the degree of nephrotoxicity caused by cyclosporine.  相似文献   

17.
目的评价局部应用外源性转化生长因子β1(TGF-β1)抗体对端端吻合神经远端再生的影响。方法选用雄性SD大鼠48只,随机分为2组,TGF-β1组和生理盐水对照组各24只;行坐骨神经切断吻合术,切口分别注入TGF-β1抗体和生理盐水各30μL;术后4,12周取材进行大体观察及电生理、超微结构和病理学染色检测。结果12周时神经电生理检查,4,12周行MESSION染色、电镜等方面均显示实验组神经再生均优于对照组。结论TGF-β1抗体对大鼠神经再生有明显促进作用。  相似文献   

18.
The calcineurin inhibitor cyclosporine A (CsA) is a widely used immunosuppressive agent. However, nephrotoxicity is a serious side effect observed in patients which limits clinical use of CsA. CsA nephrotoxicity is associated with tubulointerstitial injury progressing to nephropathy. This is typically diagnosed by invasive renal biopsy and is often only detected when the disease process is well advanced. Therefore identification of novel, early indicators of CsA nephrotoxicity could be clinically advantageous. This study aimed to establish a murine model of CsA nephrotoxicity and to identify urinary proteins that may indicate the onset of CsA-induced nephropathy using 2-D gel electrophoresis. CsA nephrotoxicity was induced in CD-1 mice by daily CsA administration for 4 weeks. By week 4, elevated serum creatinine and proteinuria were observed after CsA treatment indicating significant renal dysfunction. Decreased cadherin-1, increased α-smooth muscle actin and fibroblast specific protein 1 in kidney tissue indicated disruption of normal tubular architecture. Alterations in podocin and uromodulin were also observed which may indicate damage to other segments of the nephron. Proteomic analysis of urine identified a number of differentially regulated proteins that may be involved in early CsA nephropathy including cadherin 1, superoxide dismutase and vinculin. These findings suggest novel mechanisms of CsA nephrotoxicity and identify novel potential markers of the disease.  相似文献   

19.
Calcineurin (CaN) plays an important role in glomerular hypertrophy and extracellular matrix accumulation in early diabetic nephropathy. Cyclosporine (CSA), a CaN inhibitor, has been shown to reduce renal injury in streptozotocin-induced diabetic rats. We examined whether FK506, which immunosuppressive action was 10–100 times of CSA, inhibits progression of diabetic nephropathy in experimental diabetic rats. Diabetes was induced with streptozotocin in rats, and FK506 (0.5 or 1.0 mg/kg) was orally administered once a day for 4 weeks. Increased relative kidney weight was significantly reduced by FK506 treatment with 1.0 mg/kg (p < 0.05), and elevated 24 hour urinary albumin excretion rate was markedly attenuated by FK506 treatment with 0.5 and 1.0 mg/kg (p < 0.05, 0.01). Elevated glomerular volume was significantly attenuated by FK506 treatment with 0.5 and 1.0 mg/kg (p < 0.05), and increased indices for tubulointerstitial injury were only ameliorated by FK506 treatment with 1.0 mg/kg (p < 0.01). Western blot analysis noted that the expression of CaN protein was increased 2.4 fold in the kidney from diabetic rats, and FK506 treatment with 0.5 and 1.0 mg/kg could reduce increased expression of CaN protein by 38.0% and 73.2%. The expression of 1α (IV) collagen, p65, p-p65, OPN, α-SMA and TGF-β1 protein in kidney was significantly increased in diabetic rats and reduced by FK506 treatment (p < 0.05, 0.01). Our results show that FK506 could ameliorate renal injury in early experimental diabetic rats, which mechanism may be at least partly correlated with suppression on increased CaN in renal tissue in diabetic rats.  相似文献   

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