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1.
红景天甙对肝纤维化大鼠Samds基因表达的影响   总被引:13,自引:0,他引:13  
目的: 观察红景天甙对肝纤维化大鼠TGFβ-Smad通路的影响.方法: CCl4诱导大鼠肝纤维化,以红景天甙水溶液干预性治疗,Masson染色观察肝组织胶原沉积;ELISA法检测大鼠血清TGFβ1水平;原位杂交(in situ hybridization,ISH)和免疫组化(immunohistochemistry,IH)检测大鼠肝组织Smads表达情况.结果: 红景天甙干预性治疗使肝纤维化大鼠血清TGFβ1水平明显下降[(53.4±19.5) vs (88.7±22.8) mg/L, P<0.05],肝脏胶原占肝组织面积比例减少为(0.041±0.011)[模型组(0.167±0.052),P<0.05];治疗组肝脏Smad 4蛋白表达阳性率降低为(0.023±0.008)[模型组(0.137±0.090),P<0.01],Smad 4 mRNA阳性率降低为(0.233±0.018)[模型组(0.741±0.091),P<0.01];Smad 7蛋白阳性率增加为(0.067±0.010)[模型组(0.019±0.002),P<0.05],Smad 7 mRNA阳性率增加为(0.198±0.011)[模型组(0.074±0.012),P<0.01];肝组织Smads蛋白表达与Smads mRNA水平变化一致.结论: 红景天甙防治可显著降低肝纤维化大鼠血清TGFβ1水平,减少肝脏胶原沉积,抑制肝脏Smad 4表达及促进Smad 7 mRNA表达,从而减弱了由TGFβ1介导的肝纤维化信号,可能是其发挥抗肝纤维化作用的分子机制之一.  相似文献   

2.
TGFβRII-siRNA对肝星状细胞TGFβR/Smad信号通路的影响   总被引:1,自引:1,他引:0  
目的:研究转化生长因子βⅡ型受体小干扰RNA(TGFβRⅡ-siRNA)对肝星状细胞TGFβR/Smad信号通路的影响。方法:构建TGFβRⅡ-siRNA的表达质粒,将TGFβRⅡ-siRNA质粒采用脂质体转染HSC-T6细胞。转染72 h后,采用半定量RT-PCR检测TGFβRⅡ、Samd2、Smad3、Smad7的mRNA的表达变化,放射免疫法测上清液Ⅲ型前胶原、IV型胶原和透明质酸含量变化。结果:与无关siRNA比较,TGFβRⅡ、Smad2和Smad3 mRNA表达差异有显著性(P〈0.01),但Smad7表达差异无显著性,上清液Ⅲ型前胶原、IV型胶原和透明质酸含量明显减少(P〈0.01)。结论:TGFβRⅡ-siRNA下调TGFβRⅡ、Samd2、Smad3 mRNA表达,减少肝星状细胞胶原合成,但对Smad7 mRNA无明显下调。  相似文献   

3.
目的:研究舒肝胶囊的主要药理学作用.方法:通过采用D-氨基半乳糖造成急性肝损伤法和采用四氯化碳造成慢性肝损伤法,观察舒肝胶囊对肝脏各生化指标(AST、ALT、TP、ALB、A/G、T-BIL、GLU)的影响.结果:舒肝胶囊能降低血清中AST、ALT、T-BIL含量、升高血清中TP、ALB、GLU、TP、ALB含量.结论:舒肝胶囊对D-氨基半乳糖急性肝损伤和对四氯化碳慢性肝损伤具有一定的保护作用.  相似文献   

4.
龚作炯  宋仕玲  黄砚青  阮鹏 《华中医学杂志》2004,28(3):175-176,182,F004
目的 观察缬沙坦抗大鼠肝纤维化的疗效及作用机制。方法 将 80只Wistar大鼠随机分为 5组 ,每组 16只大鼠 ,A组为正常对照组 ,B、D组为肝纤维化模型组 ,C、E组为缬沙坦治疗组。B、C、D和E组大鼠均给四氯化碳 8W诱导肝纤维化 ,C、E组大鼠分别于第 1、4W予以缬沙坦灌胃治疗。A、B、C组大鼠于第 8W处死 ,D、E组大鼠于第 12W处死。结果 与模型组比较 ,治疗组肝内TGFβ1与TGFRⅡmRNA以及Smad3表达明显降低 ,而Smad7的表达增加 ,Smad3的免疫阳性反应信号主要位于纤维间隔中的细胞浆 ,Smad7则主要在肝细胞浆表达。大鼠肝组织TGFβ1与TGFRⅡmRNA、Smad3与Smad7在C组与E组表达比较差异有显著性 (P <0 .0 5 ) ,而B组与D组TGFβ1与TGFRⅡmRNA、Smad3与Smad7比较差异无显著性。结论 缬沙坦减轻肝脏损伤及纤维化程度的机制与抑制肝内TGFβ1与TGFRⅡmRNA及Smad3表达 ,促进Smad7表达有关。  相似文献   

5.
目的观察藏药帕珠丸对酒精性肝损伤大鼠肝组织IL-1、IL-6、TNF一α、TGF—β1含量及TGF—β1 mRNA表达的影响。方法分别给予慢性酒精性肝损伤模型大鼠50、100、200mg·kg^-1帕珠丸混悬液,观察其对肝组织IL-1、IL-6、TNF—α、TGF—β1含量及TGF—β1 mRNA表达的影响。结果藏药帕珠丸低、中、高剂量组肝组织IL-1、IL-6、TNF-α、TGF—β1含量均显著降低(P〈0.05),TGF—B,mRNA表达下降(P〈0.05)。结论藏药帕珠丸可能是通过降低肝组织中IL-1、IL-6、TNF-α、TGF—β1含量及TGF—β1 mRNA表达,对大鼠慢性酒精性肝损伤发挥保肝作用。  相似文献   

6.
目的在传统CCl4急性肝损伤模型的基础上,构建启动大鼠肝组织中的TGF-β/Smad信号传导通路的急性肝损伤动物模型。方法将30只大鼠随机分为3组,每组各10只,分别为模型组,对照组和空白组,模型组大鼠予小动脉夹夹闭肝总动脉15min手术处理,随后分别在第6天和第10天,予25%CCl4花生油溶液6mL/kg体重腹腔注射;对照组则单用两次CCl4,空白组不做任何处理;第二次CCl448h后处死所有动物。结果模型组与对照组及空白组比较:血清指标ALT、AST、HA显著上升(P0.01);肝组织HE染色病理观测,肝组织出现明显炎症、变性、坏死,纤维组织增生等现象;PT-PCR检测Ⅰ、Ⅲ型胶原、TGF-β1、Smad3mRNA表达显著增强(P0.01);免疫组化检测Ⅰ、Ⅲ型胶原、TGF-β1、Smad3蛋白的表达增强(P0.01)。结论成功启动急性肝损伤大鼠肝组织中的TGF-β/Smad信号传导路,该急性肝损伤动物模型兼备肝纤维化活跃,和TGF-β/Smad信号传导通路信号增强特征,在评价早期抗肝纤维化药物及方法时具有耗时少、有效和经济的特点,值得进一步研究。  相似文献   

7.
目的探讨肝纤维化过程中转化生长因子β1(transforming growth factorβ,TGFβ1)/Smads/细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)通路的相互作用。方法体外分离培养大鼠肝星状细胞(hepatic stellatecell,HSC),MTT法筛选丹参素最适浓度;以最适浓度丹参素及ERK阻断剂(PD98059)作用于经TGFβ1处理的HSC,CCK-8法检测各组HSC增殖;免疫细胞化学染色法检测各组HSC内α-平滑肌肌动蛋白(α-smooth muscle sctin,α-SMA)及Ⅰ、Ⅲ型胶原表达;RT-PCR检测各组HSC的Smad2、Smad3、Smad7 mRNA表达量;Western blot法检测各组Smad2/3、ERK1/2蛋白磷酸化及Smad7蛋白水平。结果 0.062 5~0.25 mmol/L的丹参素可有效抑制HSC增殖,作为最适处理浓度;PD98059(100μmol/L)可抑制TGFβ1诱导的HSC增殖,丹参素剂量依赖性抑制TGFβ1诱导的HSC增殖(P<0.01);TGFβ1促进细胞内α-SMA及Ⅰ、Ⅲ型胶原表达,PD98059及丹参素降低TGFβ1诱导的α-SMA及Ⅰ、Ⅲ型胶原水平;PD98059可拮抗TGFβ1诱导的Smad2、Smad3、Smad7 mRNA的表达(P<0.05,P<0.01),丹参素下调Smad2、Smad3 mRNA水平,但上调Smad7 mRNA水平(P<0.01);PD98059及丹参素抑制TGFβ1诱导的Smad2/3、ERK1/2蛋白磷酸化(P<0.01),但对TGFβ1诱导的Smad7蛋白表达上调有不同效应(P<0.01)。结论 TGFβ1上调Smad2、Smad3 mRNA表达及蛋白磷酸化,进而诱导HSC增殖、活化及胶原合成,ERK通路可能参与HSC中TGFβ1诱导Smad基因表达及蛋白磷酸化过程。丹参素对TGFβ1/Smad/ERK信号通路具有抑制效应。  相似文献   

8.
目的 :研究TGF - β1、Smad3蛋白在血吸虫病肝纤维化家兔肝组织中的表达及意义。 方法 :日本血吸虫尾蚴腹贴法制备家兔肝纤维化模型 (n =32 ) ,按诱导时间将动物随机分为 4、8、12周及正常对照共 4组 ,采用逆转录多聚酶链反应 (RT -PCR)检测肝组织中转化生长因子TGF - β1mRNA表达水平 ,免疫组织化学法检测Ⅰ型胶原的表达 ,同时应用Westernblot检测Smad3蛋白的表达。结果 :肝纤维化形成过程中TGF - β1mRNA表达进行性增强 ,且伴有肝组织Ⅰ型胶原含量的明显增高 ,两者呈正相关 (r =0 .6 2 9,P <0 .0 1)。与正常对照组相比 ,各期肝纤维化家兔肝组织中Smad3蛋白表达增加 ,与TGF - β1mRNA表达趋势基本一致。该Smad蛋白上调与肝纤维化程度呈明显正相关 (r =0 .5 2 7,P <0 .0 1)。结论 :TGF - β1/Smad信号通路参与了血吸虫病肝纤维化进程 ,Smad3的上调在肝纤维化发生、发展中起重要的介导作用。  相似文献   

9.
目的探讨鳖甲煎丸对四氯化碳诱发肝纤维化大鼠转化生长因子-β/Smads信号传导通路的干预作用,并阐述各项指标之间的内在联系。方法采用皮下注射四氯化碳配合高脂饮食制备肝纤维化模型,观察鳖甲煎丸对肝纤维化模型大鼠血清TGF-β1及肝组织Smad3和Smad7蛋白表达的影响,并以西药秋水仙碱片作对照。结果鳖甲煎丸能减轻肝细胞变性,减少胶原的合成与分泌,减轻纤维组织增生,明显抑制大鼠血清TGF-β1及肝组织Smad3的表达,增高Smad7的表达。结论鳖甲煎丸可有效防治大鼠肝纤维化,其作用机制与调控TGF-β1和Smads蛋白表达有关。  相似文献   

10.
目的研究小柴胡汤通过转化生长因子-β1(TGF-β1)/Smad通路改善大鼠肝纤维化的作用及机制。方法雄性SD大鼠随机分为对照组、模型组、中药组、中药+SRI组,采用四氯化碳皮下注射的方式建立大鼠肝纤维化模型,给与小柴胡汤灌胃及Smad2/3激活剂SRI-011381腹腔注射干预。比较各组大鼠肝脏病理改变、血清天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、白蛋白(ALB)、透明质酸(HA)、层粘蛋白(LN)、Ⅲ型前胶原(PCⅢ)含量,以及肝脏中TGF-β1、Smad2、Smad3表达的差异。结果与对照组比较,模型组大鼠出现了典型的肝纤维化病理改变,血清中ALB的含量降低,血清中ALT、AST、HA、LN、PCⅢ的含量及肝脏中TGF-β1、Smad2、Smad3的表达水平增加;与模型组比较,中药组大鼠肝纤维化的病理改变减轻,血清中ALB的含量增加,血清中ALT、AST、HA、LN、PCⅢ的含量及肝脏中TGF-β1、Smad2、Smad3的表达水平降低;与中药组比较,中药+SRI组大鼠肝纤维化的病理改变加重,血清中ALB的含量降低,血清中ALT、AST、HA、LN、PCⅢ的含量及肝脏中TGF-β1、Smad2、Smad3的表达水平增加。结论小柴胡汤能够改善大鼠的肝纤维化,抑制TGF-β1/Smad通路是介导这一改善作用可能的分子机制。  相似文献   

11.
Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P< 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P< 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.  相似文献   

12.
Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P < 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (>0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P <0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P < 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.  相似文献   

13.
Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.  相似文献   

14.
Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.  相似文献   

15.
Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.  相似文献   

16.
A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care(~'4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.  相似文献   

17.
Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.  相似文献   

18.
Journal of Nanjing Medical University (English Edition) JNMU, sponsored by Nanjing Medical University, was established in 1987. It is a bimonthly comprehensive English medical journal published locally and abroad.Since 2007, Journal of Nanjing Medical University (English Edition )was granted Elsevier the full publishing and distribution rights worldwide for the Electronic Edition, excluding the People's Republic of China.  相似文献   

19.
Objective To measure Derpl and Blot5 allergen levels in asthmatics' homes in Hongkong.Methods Seventy houses were enrolled for a mite indoor environment study. Dust samples were obtained from two sites of each patients' house: bed and floor. Derpl and Blot5 levels were quantified by a two-site monoclonal antibody-based ELISA technique.Results The levels of Derpl allergens found in bed (geometric mean (GM) 3.43 μg/g of dust; 95%CI, 1.89-4.96 μg/g)and on the floor (GM 1.12 μg/g of dust; 95%CI, 0.71-1.53 μg/g) indicated significant differences (P=0.005). However, the levels of Blot5 allergens found in bed (GM 19.00 μg/g of dust; 95%CI, 0.89-38.90 μg/g) and on the floor (GM 6.14 μg/g of dust; 95%CI, 0.40-11.90 μg/g) showed no statistically significant difference. In addition, in regards to the exposure index for Derpl and Blot5 allergens found in bed and on the floor, 17.6% in bed and 8.6% on the floor had levels of Blot5 ≥ 10 μg/g of dust, higher than those obtained for Derp1 (7.2% and 0% in bed and on the floor respectively, P< 0.05); higher percentages in bed and on the floor (25.0% and 35.7%) were observed for levels of Blot5 =0 μg/g of dust as compared with Derpl in bed and on the floor (4.3% and 14.5% respectively, P< 0.05).Conclusions Derpl and Blot5 are the major allergens found in this regional study, Blot5 is a more potent allergen in Hongkong, probably reflecting the high level of exposure to Blomia tropicalis (Bt). Bt and Dermatophagoides pteronyssinus (Dp) allergens should be included for precise diagnosis and effective immuno-therapeutic treatment of mite allergy in Hongkong.  相似文献   

20.
ANTI-PROLIFERATION EFFECT OF ORIDONIN ON HL-60 CELLS AND ITS MECHANISM   总被引:4,自引:0,他引:4  
Objcetive To investigate the anti-proliferation effect of oridonin on leukemic HL-60 cells and its mechanism. Methods HL-60 cells in vitro in culture medium were given different concentrations of oridonin. The inhibitory rate of cells were measured by microculture tetrazolium (MTT) assay, cell apoptotic rate was detected by flow cytometry (FCM), morphology of cell apoptosis was observed by hoechst 33258 fluorescence staining, and the activity of telomerase was detected using telomere repeat amplification protocol (TRAP) PCR-ELISA before and after apoptosis occurred. Results Oridonin could decrease telomerase activity, inhibit growth of HL-60 cells, and cause apoptosis significantly. The suppression was both in time- and dose-dependent manner. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed clearly by hoechst 33258 fluorescence staining especially after cells were treated 48-60 hours by oridonin. Conclusions Oridonin has apparent anti-proliferation and apoptotic effects on HL-60 cells in vitro, decreasing telomerase activity of HL-60 cells may be one of its most important mechanisms. These results will provide strong laboratory evidence of oridonin for clinical treatment of acute leukemia.  相似文献   

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