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1.
骨成形蛋白-7在大鼠肾小管间质损害中的作用   总被引:8,自引:1,他引:8  
目的观察单侧输尿管梗阻(UUO)大鼠中骨成形蛋白-7(BMP-7)在肾小管间质中的表达部位、动态变化及其与肾小管间质损害的关系。方法60只Wistar大鼠随机分为正常大鼠组、假手术组和单侧输尿管梗阻组,分别于术后1d、3d、7d、14d处死。采用RT-PCR方法检测BMP-7mRNA、TGF-β1.mRNA表达水平,免疫组化方法检测肾小管间质中BMP-7、TGF-β1、α-SMA的蛋白定位、表达及其与输尿管梗阻后肾小管间质损害的关系。结果与对照组相比,BMP-7mRNA于术后第1天即出现表达下降并随梗阻时间延长递减;而TGF-β1mRNA则随梗阻时间延长而递增(P均<0.05)。BMP-7蛋白在对照组中高度表达,主要分布在肾小管及肾间质,肾小球内基本无表达。在梗阻组随着肾间质损害的加重,BMP-7蛋白表达呈进行性下降,第14天表达量最弱,几乎没有明显的阳性表达,而TGF-β1、α-SMA蛋白表达则逐渐增加(P均<0.01)。BMP-7与TGF-β1蛋白表达阳性面积成显著负相关(r=-0.875,P<0.05)。BMP-7与α-SMA蛋白表达阳性面积亦成显著负相关(r=-0.843,P<0.05)。结论BMP-7于肾小管间质病变早期即出现表达下调,早于肾间质纤维化的出现,其表达量与肾间质TGF-β1、α-SMA表达负相关且随间质病变进展进行性下降。BMP-7表达下调可能参与介导肾小管间质损害的发生发展。  相似文献   

2.
目的 探讨转化生长因子β(TGF-β)Ⅰ型受体(RⅠ)、Ⅱ型(RⅡ)受体以及下游Smad蛋白在单侧输尿管梗阻(UUO)大鼠模型肾脏中表达及意义。 方法 90只雌性Wistar大鼠随机分为正常对照组(CON组)、假手术组(SOR组)和单侧输尿管梗阻组(UUO组),分别于术后1、3、7、14、21 d处死,检测各组大鼠肾功能;PAS与Masson染色观察大鼠肾间质病理形态改变;实时定量PCR基因芯片分析正常大鼠和肾间质纤维化大鼠肾组织TGF-βⅠ、Ⅱ、Ⅲ型受体及Smad蛋白家族表达。筛选出差异表达的受体亚型,进一步应用实时荧光定量PCR、蛋白免疫印迹法、免疫荧光法检测和验证筛选出的差异受体亚型在不同分期肾间质纤维化大鼠肾组织的分布和表达。 结果 与CON组相比,UUO组大鼠的Scr及BUN于术后3 d开始升高(P < 0.05),第21天达峰值(P < 0.01);UUO组术后3 d肾间质可见明显炎性细胞浸润;14 d后出现明显肾小管萎缩;21 d可见明显肾间质纤维化。UUO组肾组织TGF-βⅠ型受体ALK-5、ALK-7和TGF-βRⅡ的mRNA表达于术后3 d上升并随梗阻时间延长逐渐增加(P < 0.05),于14 d达到峰值(均P < 0.01);ALK-6的mRNA表达于术后3 d下降(P < 0.05)并随梗阻时间延长逐渐减少,于14 d达谷值(P < 0.01)。ALK-5、ALK-6、ALK-7和TGF-βRⅡ蛋白表达与基因表达一致。Smad2/3及磷酸化(p)-Smad2/3的蛋白表达于术后3 d上升(均P < 0.05)并随梗阻时间延长逐渐增加,于14 d达到峰值(均P < 0.01)。 结论 在肾间质纤维化进展中不同TGF-β受体亚型存在不同的变化规律并与肾间质纤维化进展密切关联。  相似文献   

3.
目的:探讨甘草酸二胺对肾间质纤维化的作用及其机制。方法:以Wistar大鼠单侧输尿管梗阻(UUO)为模型,在不同的时间点(7d、14d、28d)观察梗阻侧肾间质纤维化指数;致纤维化的转化生长因子β1(TGF-β1)的表达情况;肾皮质中与肾脏纤维化相关的Smurf2、Smad7信号蛋白等的mRNA及蛋白表达。结果:(1)随着梗阻时间的延长,肾间质纤维化程度逐渐加重,Smurf2基因和蛋白质明显上调,呈时间依赖性(P〈0.01);Smad7蛋白呈时间依赖性下调(P〈0.01),Smad7基因在各个时间点无明显变化;TGF-β1基因在UUO后第7d达高峰,此后逐渐下降,但仍然高于假手术组(P〈0.01)。(2)甘草酸能改善UUO所致的肾间质纤维化程度(P〈0.01),下调肾脏组织TGF-β1基因的表达(尸〈0.01);减少Smurf2基因和蛋白质的表达,同时上调TGF-β1信号传导中抑制性因子Smad7的表达(P〈0.01)。结论:甘草酸二胺能保护UUO所致的肾间质纤维化损伤。其可能的作用机制为减少Smurf2核酸和蛋白质的表达,增加抗纤维化作用的Smad7蛋白表达;减少TGF-β1表达,阻止TGF-β1信号传导,从而阻断肾间质的纤维化。  相似文献   

4.
Smad 6和Smad 7基因治疗对肾小管间质纤维化进程的影响   总被引:4,自引:2,他引:2  
目的 观察腺相关病毒(rAAV)介导的Smad6和Smad7基因治疗对单侧输尿管梗阻性(LIUO)肾小管间质纤维化进程的影响。方法 构建产生表达Smad6和Smad7基因的无辅毒腺相关病毒载体,再将此病毒颗粒通过肾动脉途径转移到UUO模型。30只Wistar大鼠随机分为假手术组、梗阻组、LacZ AAV转染组、Smad6 AAV转染组和Smad7 AAV转染组(n=6),于术后第3周处死大鼠。采用β-半乳糖苷酶染色和免疫组化观察外源基因的定位,Western印迹法观察外源基因、胞内磷酸化Smad2、PAI-1和α-SMA的表达;底物酶谱法检测MMP-2和MMP-9活性,分光光度法测定肾组织羟脯氨酸含量。结果 Smad6和Smad7成功地转染到外髓的肾小管间质区,定位在肾小管和集合管细胞,而血管细胞、肾小球或间质细胞均未见有AAV转移基因的表达。Smad7基因治疗可显著降低肾组织PAI-1、α-SMA的表达和肾组织羟脯氨酸含量,增加MMP-2和MMP-9活性,这些作用与Smad7阻断Smad2磷酸化有关。相反,Smad6没有这样的治疗作用。结论 Smad7基因转移能有效缓解单侧输尿管梗阻肾小管间质纤维化,AAV介导的Smad7基因转移有望成为治疗肾小管间质纤维化的方法之一。  相似文献   

5.
目的:研究肾纤康对单侧输尿管梗阻(UUO)大鼠肾组织转化生长因子β1(TGF-β1)、Smad2、Smad3、Smad7表达的影响,探讨肾纤康防治肾间质纤维化的作用机制。方法:将40只大鼠随机分为4组,即假手术组、模型组、肾纤康组、苯那普利组,采用左侧输尿管梗阻方法造模,用免疫组织化学方法作肾间质TGF-β1、Smad2、Smad3、Smad7检测,并观察肾脏病理学变化。结果:模型组和各治疗组肾间质TGF-β1、Smad2、Smad3面积比增加,Smad7面积比减少,与假手术组相比差异有统计学意义(P〈0.05)。与模型组相比,药物治疗组肾间质TGF-β1、Smad2、Smad3面积比减少,Smad7面积比增加,差异有统计学意义(P〈0.05)。肾纤康组与苯那普利组肾间质TGF-β1、Smad2、Smad3、Smad7面积比差异无统计学意义(P〉0.05)。结论:肾纤康通过下调TGF-β1、Smad2、Smad3在肾间质的表达及增加Smad7的表达而抑制单侧输尿管梗阻(UUO)大鼠肾间质纤维化,与肾纤康可调节TGF-β1/Smad信号转导通路有关,其作用与苯那普利差异无统计学意义。  相似文献   

6.
人参皂甙Rg1对梗阻肾的保护作用   总被引:9,自引:0,他引:9  
目的:探讨人参皂甙Rg1(G- Rg1)对梗阻肾的保护作用。方法:建立大鼠单侧输尿管梗阻(UUO)模型。假手术组:未行输尿管结扎即关腹;非治疗组:行左侧输尿管结扎后关腹;G- Rg1 组:行左侧输尿管结扎后关腹,并给予G -Rg1灌胃[120 mg/(kg·d)]。全部大鼠1 周后处死,取出左肾常规固定。免疫组织化学染色法检测Bax、PCNA、TGF -β1蛋白表达水平,并应用计算机图文系统进行分析。结果:UUO大鼠肾小管上皮细胞、肾间质细胞中Bax、PCNA蛋白表达显著增多,肾间质、肾小球中TGF- β1 蛋白表达显著增多。G- Rg1 明显抑制UUO大鼠肾小管上皮细胞中Bax蛋白表达(P<0.05),促进PCNA蛋白表达(P<0.05);抑制肾间质和肾小球中TGF- β1蛋白表达(P<0.05)。结论:Bax在梗阻肾小管上皮细胞凋亡、TGF- β1 在间质纤维化和肾小球硬化中可能起着重要的作用。G -Rg1可能有抑制梗阻肾小管上皮细胞凋亡、促进上皮细胞增殖、抑制间质纤维化和肾小球硬化的作用。  相似文献   

7.
目的:探讨肾衰饮抗肾纤维化分子生物学机制。方法:采用腺嘌呤肾病模型,随机将60只SD大鼠分为空白组、模型组、肾衰饮组与尿毒清组,采用RT-PCR观察肾衰饮对CRF大鼠TGF-β1mRNA表达的影响;ELISA法检测Smad2、Smad3、Smad7蛋白表达;免疫组化法检测α-SMA蛋白表达。结果:模型组与正常组比较TGF-β1mRNA表达增强,Smad2、Smad3水平升高,Smad7下降,治疗后肾衰饮组TGF-β1mRNA表达明显减少,Smad2、Smad3水平下降,Smad7升高,同时肾组织α-SMA表达下降,明显优于尿毒清(P0.05)。结论:肾衰饮抑制TGF-β1mRNA表达,提高Smad7水平,通过调节TGF-β1/Smad信号通路,以抑制肾纤维化的发生、发展。  相似文献   

8.
目的:研究地龙组分对单侧输尿管结扎大鼠BMP-7、Smad6、TGF-β_1表达的影响,探讨地龙组分延缓肾纤维化的可能机制。方法:健康雄性wistar大鼠60只,随机分组:假手术组+模型组+地龙低剂量组+地龙高剂量组。采用单侧输尿管结扎法复制肾间质纤维化大鼠模型,取梗阻侧肾组织标本,免疫组织化学方法检测肾组织BMP-7、Smad6、TGF-β_1的表达。结果:地龙治疗组大鼠的肾间质纤维化有所改善;与模型组相比,地龙治疗组大鼠肾组织BMP-7、Smad6表达增多,TGF-β_1表达下降(P0.05)。结论:地龙组分通过上调BMP-7、Smad6表达,下调TGF-β_1的表达,来延缓肾纤维化的进程。  相似文献   

9.
目的 探讨肾淋巴循环障碍对大鼠肾小管间质纤维化的作用及其与TGF-β1、Smad2/3表达变化的关系。 方法 雄性Wistar大鼠48只,随机分为淋巴循环障碍模型组和假手术对照组各24只。分别在术后1、2、4、8周每组各处死6只。测定尿蛋白量(24 h)和Scr。PAS和Masson染色观察肾组织病理改变。用实时PCR检测TGF-β1、Smad2/3、I型胶原(ColⅠ)mRNA的表达量。用免疫组化和(或)Western 印迹方法检测肾组织ColⅠ、TGF-β1、Smad2/3和磷酸化Smad2/3(p-Smad2/3)的蛋白表达量及主要表达部位。 结果 模型组大鼠尿蛋白显著增加,随着时间推移肾功能逐渐减退,并出现明显的组织病理改变,小管间质损伤指数明显高于对照组(P < 0.05或P < 0.01),并随时间延长而逐渐加重。肾组织中ColⅠ、TGF-β1、Smad2/3、p-Smad2/3的蛋白和(或)基因表达水平也明显增高(P < 0.01),且主要表达在肾小管上皮细胞及肾间质。 结论 肾淋巴循环障碍可导致大鼠肾脏功能及小管间质的损害,并随着时间的延长而加重。其作用机制可能与激活TGF-β-Smad途径,导致肾小管间质纤维化有关。  相似文献   

10.
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。  相似文献   

11.
In Spain, the number of donors per million of population and the activity of transplantation is a direct consequence of the continued work of the hospital transplant coordinators. There are 146 procurement hospitals with approximately 534 transplant coordinators (13.6 coordinators per hospital and 12.7 per million of population). A voluntary survey of 74 Spanish transplant coordinators revealed 67.6% to be men and 32.4% women of average age 43 years with specialization of 75.7%, Intensive Care Medicine; 8.1%, Anesthesiology; 6.7%, Nephrologists; and the rest, General Surgery or without any specialization. Among the group who responded to the injury, 86.5% were doctors and 13.5%, nurses. The overall team is composed of 52% doctors, 27.7% nurses and others with 70.3% working part-time and 27%, full-time. Previous experience was noted to be less than 5 years among 51.4%, and more in the rest of the cases. The 85% work under medical direction by management. Their payment includes salary plus activity in 48.7% of the cases; 21.6%, only salary, and 18.9%, only activity. Each coordinator generates between 3 and 7 organ as well as 3 and 11 of tissue donors. In conclusion, comparing this data with the practice in the United States demonstrates the unique aspects of the Spanish system.  相似文献   

12.
The relation of plasma concentration of d-tubocurarine (dTc) to neuromuscular blockade, and the distribution and urinary excretion of dTc was determined in neonates (n = 4), infants (n = 6), children (n = 8), and adults (n = 8). The plasma concentration-time course curves to 24 hr are best described for all groups by three-compartment models. Both neonates and infants exhibit decreased plasma clearance (CLP), 1.1 +/- 0.08 and 1.0 +/- 0.06 ml X kg-1 X min-1, and in addition a prolonged t1/2 terminal phase, 311 +/- 44 and 306 +/- 35 (mean +/- SEM, min). The neonates' 24-hr urinary excretion, 27 +/- 2 (mean +/- SEM, % total dose) is significantly less than the adult value, 45 +/- 4% total dose. There was no significant difference seen in the log plasma concentration-evoked compound electromyogram (ECEMG) response between 20-80% paralysis for adults, children, infants, and five of the seven neonates studied. Two of the neonates had a significant shift of their log concentration-response curve to the right. There was also no significant difference between any of the groups in the time for 50% return of ECEMG stimulus height or the time required for recovery of the ECEMG from 25 to 75% of control value. for recovery of the ECEMG from 25 to 75% of control value.  相似文献   

13.
14.
We tested the prediction that the alveolar washin and washout, tissue time constants, and pulmonary recovery (volume of agent recovered during washout relative to the volume taken up during washin) of desflurane, sevoflurane, isoflurane, and halothane would be defined primarily by their respective solubilities in blood, by their solubilities in tissues, and by their metabolism. We concurrently administered approximately one-third the MAC of each of these anesthetics to five young female swine and determined (separately) their solubilities in pig blood and tissues. The blood/gas partition coefficient of desflurane (0.35 +/- 0.02) was significantly smaller (P less than 0.01) than that of sevoflurane (0.45 +/- 0.02), isoflurane (0.94 +/- 0.05), and halothane (2.54 +/- 0.21). Tissue/blood partition coefficients of desflurane and halothane were smaller than those for the other two anesthetics (P less than 0.05) for all tissue groups. As predicted from their blood solubilities, the order of washin and washout was desflurane, sevoflurane, isoflurane, and halothane (most to least rapid). As predicted from tissue solubilities, the tissue time constants for desflurane were smaller than those for sevoflurane, isoflurane, and halothane. Recovery (normalized to that of isoflurane) of the volume of anesthetic taken up was significantly greater (P less than 0.05) for desflurane (93% +/- 7% [mean +/- SD]) than for halothane (77% +/- 6%), was not different from that of isoflurane (100%), but was less than that for sevoflurane (111% +/- 17%). The lower value for halothane is consistent with its known metabolism, but the lower (than sevoflurane) value for desflurane is at variance with other presently available data for their respective biodegradations.  相似文献   

15.

Summary

Osteoporosis is a major public health concern for elderly subjects. Old age is a risk factor for fragility fractures; countries with aging population face a heavy burden of fractures and their consequences.

Introduction

In 2009, the total population of Argentina was 40 million, with 10 million inhabitants aged >50 years. Population will grow 13% by 2050 and reach 53 million, but the elderly population will reach 19.5 million.

Discussion

Local bone mineral density studies reveal that two out of four postmenopausal women have osteopenia, one has osteoporosis, and one has a normal bone mineral density. Around 3.3 million women will suffer from osteopenia in 2025 and 5.24 million in 2050. Although the rate of fragility fractures is higher in patients with osteoporosis, the absolute number of fractures is higher in osteopenic patients. In Argentina, the mean annual rate of hip fractures is 488/100,000 inhabitants aged above 50 years, with a 2.6:1 F/M ratio. Thus, over 34,000 hip fractures occur every year among the aged populationwith an average 90 such fractures per day.

Conclusion

The Latin American Vertebral Osteoporosis Study found an overall 16.2% prevalence of vertebral fractures in Argentinean women aged 50 years or over. Hospitalization costs of hip and vertebral fractures in Argentina exceed 190 million USD per year. Consequently, the costs of osteoporosis for the public health system are staggering; however, the federal or the provincial governments of Argentina do not give the disease a high priority. To conclude, efforts for the prevention and management of osteoporosis are urgently needed.  相似文献   

16.
OBJECTIVE: To compare various graft materials in the rabbit model, including autologous cartilage, dermal tissue, fat, and AlloDerm (a cadaver-derived material). METHODS: Twenty-five New Zealand white rabbits were used. Equally sized autogenous (fat, fascia, cartilage, and dermal) grafts and AlloDerm were implanted into subcutaneous dorsal pockets on the rabbits. Animals were killed 1, 2, 3, and 4 months after surgery. The grafts were examined microscopically for thickness, resorption, fibrosis, neovascularization, inflammation, eosinophilia, and the presence of multinucleated giant cells or microcysts. RESULTS: The cartilage grafts revealed excellent viability with no resorption. The fascial grafts showed negligible volume loss. The dermal grafts developed epidermoid cysts. The AlloDerm grafts demonstrated graft thickening at 1 month and total resorption at 3 and 4 months. The fat grafts demonstrated 30% to 60% partial resorption. CONCLUSIONS: The major disadvantage of using an autogenous fat graft was partial resorption, whereas cyst formation was observed with dermal grafts. AlloDerm caused tissue reaction and resorption. The best graft material was cartilage, with a low absorption rate, good biocompatibility, and minimal tissue reaction or fibrosis, followed by fascia, with a minimal shrinkage capacity and tissue reaction.  相似文献   

17.
为探讨烧协病人伤后血清、尿和水泡液中 Zn、Cu、Fe、Ca、Mg 的含量,观察了106例烧伤病人(L 组烧伤≥30%,TBSA,57例;S 组烧伤<30%TBSA,49例)伤后1,2,3,7,14,21,28天血清、尿和水泡液中 Zn、Cu、Fe、Ca、Mg 的动态变化。发现除血清 Fe 第1天高于正常值外,其它各元素都减低,L 组比 S 组减低明显。尿 Zn、Cu、Fe 排出明显增多,尿 Ca、Mg 排出减少。水泡液 Zn、Fe、Ca 与血清正常值近似,Cu、Mg 略低于血清正常值。说明烧伤后血 Zn、Cu、Fe、Ca、Mg 的降低与从尿液及创面丢失有关。  相似文献   

18.
为探讨烧伤病人伤后血清、尿和水泡液中Zn、Cu、Fe、Ca、Mg的含量,观察了106例烧伤病人(L组烧伤≥30%TBSA,57例;S组烧伤<30%TBSA,49例)伤后1,2,3,7,14,21,28天血清、尿和水泡液中Zn、Cu、Fe、Ca、Mg的动态变化。发现除血清Fe第1天高于正常值外,其它各元素都减低,L组比S组减低明显。尿Zn、Cu、Fe排出明显增多,尿Ca、Mg排出减少。水泡液Zn、Fe、Ca与血清正常值近似,Cu、Mg略低于血清正常值。说明烧伤后血Zn、Cu、Fe、Ca、Mg的降低与从尿液及创面丢失有关。  相似文献   

19.
Between 1 January and 31 December 1987, 1178 hip fractures were recorded in the 28 clinical centres, public and private, of the Picardy region (19443 km2, 1.8 million inhabitants). Patients under 20 years and those with metastatic cancer and myelomatous fractures were excluded. Women sustained 853 fractures (age mean ± SD: 80.2±10.4 years) and men 325 (age 69.7±16.0 years). The crude incidence rate per 10 000 person years was 13.4 for women and 5.4 for men (female/male ratio 2.6). These incidences are among the lowest recorded in Northern Europe. Women with trochanteric fractures were older than those with cervical ones, but no difference was observed for men. After adjusting for age and sex, the incidence of hip fracture was greater in urban (10.5 per 10 000 person years) and semi-rural areas (8.2) than in rural areas (5.3). The mean bed-days per patient (±SD) was 21.6±16.0 (quartiles: 13–17–26 days); no difference was observed between sex or age classes. The in-hospital mortality rate was 8.7%, it increased with age and was higher in men, whatever their age. We review the data in different countries, mostly European, to compare with the Picardy region.  相似文献   

20.
不同烧伤面积血清,尿,水泡液中Zn,Cu,Fe,Ca,Mg的动态…   总被引:12,自引:0,他引:12  
对探讨烧伤病人伤后血清,尿和水泡液中Zn,Cu,Fe,Ca,Mg的含量,观察了106例烧伤病人(L组烧伤≥30%,TBSA,57例,S组烧伤〈30%TBSA,49例)伤后1,2,3,7,14,21,28天血清,尿和水泡液中Zn,Cu,Fe,Ca,Mg的动态变化,发现除血清Fe第1天高于正常值外,其它各元素都减低,L组比S组减低明显,尿Zn,Cu,Fe排出明显增多,尿Ca,Mg排出减少,水泡液Zn,  相似文献   

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