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1.
目的探讨Akt/蛋白激酶B(PKB)信号通路在慢性移植肾肾病(CAN)早期病变中的作用。方法建立Fisher(F344)大鼠到Lewis(LEW)大鼠的左肾移植CAN模型,术后4、8、12及16周时测定24h尿蛋白定量及血肌酐水平,并进行移植肾组织学观察,免疫组化法检测移植肾组织中磷酸化Akt(p-Akt)及基质金属蛋白酶9(MMP-9)的表达,逆转录聚合酶链反应检测肾组织中p-Akt mRNA的表达水平。以单纯切除一侧肾脏的LEW大鼠和F344大鼠为对照。结果移植组术后各检测时间点的24h尿蛋白定量及血肌酐水平呈上升趋势(P〈0.05),其组织学改变的Banff评分也呈上升趋势(P〈0.05)。移植组各时间点的p-Akt及p-Akt mRNA表达水平均显著高于LEW对照组和F344对照组,且随时间的延长逐步增高(P〈0.05);移植组MMP-9表达水平在术后4、8周显著高于LEW对照组和F344对照组(P〈0.05),术后16周显著低于LEW对照组和F344对照组(P〈0.05)。结论在CAN早期的肾组织中,p-Akt及MMP的表达上调,其表达水平与肾组织的病理改变程度呈正相关,它们可能在CAN早期的发生进展中发挥重要作用。  相似文献   

2.
目的观察比较不同性别供体的移植肾慢性排斥反应。方法以雄性Lewis大鼠作受体,以雄、雌Fisher大鼠作供体,分为两组进行同种肾移植,建立大鼠同种肾移植慢性排斥反应动物模型。移植后每4周检测受者的24h尿蛋白、血肌酐、肌酐清除率;移植后24周处死受体大鼠,对移植肾进行显微镜检、免疫组化、核糖核酸酶保护测定等检测,对比两组数据评价供体性别对移植肾的影响。结果两组比较,第20周雄性供体组的24h尿蛋白(21.14±0.98)mg/24h、肌酐清除率(0.35±0.01),雌性供体组24h尿蛋白(24.15±2.38)mg/24h、肌酐清除率(0.33±0.02),具有明显差异,雌性供体组的肾功能明显严重受损。雄性供体组移植肾仅有低度间质纤维化和轻微的血管内膜增厚,肾小球硬化百分数(19.7±4.2)%,淋巴细胞CD5’数量(14.94-3.0),雌性供体组移植肾间质纤维化和血管内膜增厚更严重,肾小球硬化百分数(23.9±3.92)%,淋巴细胞CD5’数量(17.3±1.0),雌性供体组均高于雄性供者组,有统计学意义。雄性组TGF-B(0.01434-0.0031)和IL-6(0.0018±0,0024)的mRNA表达比雌性组TGF-B(0.0092±0.0018)和IL-6(0.000644-0.00022)高。结论在大鼠同种肾移植慢性排斥动物模型上,供体的性别对移植肾的功能和组织形态具有明显的影响。  相似文献   

3.
目的研究大鼠慢性同种移植肾病肾组织中Smad7的表达及意义。方法制作原位肾移植大鼠模型,分别于4周、8周、12周、16周及24周处死大鼠,检测24h尿蛋白定量、肾功能;移植肾组织标本切片行光镜检测;免疫组织化学与免疫印迹、逆转录-多聚酶链反应方法检测肾组织中Smad7蛋白、Smad7mRNA的表达;免疫印迹方法检测肾组织p-smad2/3蛋白的表达水平,逆转录-多聚酶链反应方法检测肾组织转化生长因子-81mRNA的表达。结果移植组大鼠尿蛋白定量、血清肌酐水平于移植后16周时显著增高,24周时更为显著。Smad7蛋白在移植组逐渐降低,24周时降至最低,为对照组的15%。Smad7mRNA在移植后4周即升高,随着移植时间逐渐延长,24周时为对照组的2.73倍(P〈0.01);p-smad2/3在移植后随疾病进展逐渐升高,24周时达高峰。免疫组织化学结果显示Smad7主要表达在小管间质。相关分析显示,肾移植大鼠Smad7蛋白表达水平与24h尿蛋白定量、血清肌酐水平、肾间质纤维化程度呈负相关(P〈0.05,P〈O.01)。结论Smad7蛋白表达下调在慢性同种移植肾病发病机制中起重要作用。  相似文献   

4.
目的 探讨雄激素受体拮抗剂氟他胺对移植肾慢性排斥反应的影响.方法 以雄性Lewis大鼠作受者,以雌、雄Fisher大鼠作供者,建立大鼠同种肾移植慢性排斥反应动物模型.用雄激素受体拮抗剂氟他胺按25 mg/kg体重喂食试验组20周,移植后每4周检测受者的24 h尿蛋白、血肌酐、肌酐清除率;移植后20周处死受者大鼠,对移植肾进行显微镜检、免疫组织化学、核糖核酸酶保护测定等检测,对比试验组与对照组数据评价氟他胺对移植肾的影响.结果 两组比较,不论雄性供者还是雌性供者的大鼠的24 h尿蛋白、肌酐清除率具有明显的差异,试验组的肾功能受损较轻.两组移植肾组织血管内膜增厚、肾小球硬化和间质纤维化程度以及单核巨噬细胞细胞浸润,转化生长因子(TGF)-β和白细胞介素(IL)-6的mRNA表达程度差异均有统计学意义,试验组组均低于对照组(P<0.05).结论 在大鼠同种肾移植慢性排斥动物模型上,雄激素受体拮抗剂氟他胺可以明显抑制慢性排斥的发生.  相似文献   

5.
肾移植受者术后远期发生贫血的危险因素   总被引:1,自引:0,他引:1  
目的探讨同种肾移植受者术后远期发生贫血的危险因素。方法93例同种肾移植受者按照贫血与否分为贫血组和非贫血组,探讨免疫抑制剂、降压药物、移植肾功能以及其他伴随疾病对肾移植术后远期贫血的影响,同时检测两组血清促红细胞生成素的水平。结果贫血组女性受者,联合应用西罗莫司(SRL)和霉酚酸酯(MMF),应用血管紧张素转化酶抑制剂(ACEI)或血管紧张素Ⅱ受体拮抗剂(ARB)降压药物,血肌酐大于120μmol/L,慢性移植肾小球硬化,以及伴有巨细胞病毒(CMV)感染或者上消化道溃疡的肾移植受者均较非贫血组显著增多(P〈0.05)。贫血组促红细胞生成素(EPO)水平显著低于非贫血组(P〈0.05)。结论女性患者、联合SRL和MMF治疗、应用ACEI类或ARB类降压药,血肌酐大于120μmol/L,慢性移植肾小球硬化,以及伴有巨细胞病毒(CMV)感染或上消化道溃疡等疾病是肾移植术后远期发生贫血的危险因素。  相似文献   

6.
目的探讨早期慢性移植肾肾病(CAN)大鼠的组织学改变与转化生长因子-β1(TGF-β1)表达的关系。方法以F344大鼠为供体,Lewis大鼠为受体,建立大鼠CAN模型,分为移植组、F344对照组和Lewis对照组。观察3组大鼠肾功能、肾组织学改变及。肾组织TGF-β1的表达。结果①与F344对照组和Lewis对照组比较,移植组大鼠24h尿蛋白及血肌酐明显升高,差异有统计学意义(P〈0.05),肾组织改变以单个核细胞浸润为主,肾组织TGF-t31表达水平升高,差异有统计学意义(P〈0.05);②移植组大鼠肾组织单个核细胞浸润与TGF-β1表达呈正相关,慢性病变与TGF-β1表达无相关性。结论早期CAN功能学上表现为出现蛋白尿、血肌酐升高,组织学上表现为以单个核细胞浸润为主,并与TGF-β1表达升高呈正相关。  相似文献   

7.
目的观察大豆蛋白饮食对5/6肾切除大鼠血管早期病变的影响并探讨其可能的机制。方法把40只大鼠随机分为手术组和假手术组,手术组大鼠行5/6肾切除术后又随机分为对照组(20%酪蛋白),低蛋白组(6%酪蛋白),大豆蛋白组(6%大豆蛋白)。假手术组予以普通酪蛋白饲料饮食。于术前、术后4周、8周及12周观察大鼠的营养状况,并检测其血清尿素氮(BUN)、肌酐(Scr)、胆固醇(TC)、三酰甘油(TG)、白蛋白(Alb)以及尿蛋白量(24h)等指标。12周后处死所有大鼠,并留取其主动脉弓组织,行HE染色观察主动脉弓病理变化,并行免疫组化染色检测其单核细胞趋化蛋白(MCP)1和植物血凝素样氧化低密度脂蛋白受体(LOX)1的表达水平。结果5/6肾切除大鼠各组BUN、Scr从第4周起均开始升高,但低蛋白组及大豆蛋白组BUN、Scr上升的程度较对照组缓慢,且以大豆蛋白组最为显著[12周Scr,(111.44±5.50)比(172.00±9.54)μmol/L,P〈0.01]。与假手术组相比,5/6肾切除大鼠各组血白蛋白水平均显著降低(P〈0.01),但各手术组间差异无统计学意义。5/6肾切除大鼠各组尿蛋白量(24h)随时间的延长持续增加,但低蛋白组、大豆蛋白组的增加幅度较小(P〈0.01)。各组大鼠主动脉弓组织未见明显病理改变。免疫组化检查发现,大豆蛋白组大鼠主动脉弓内膜MCP-1(155.68±4.84比132.80±5.67)和LOX-1(195.48±4.95比167.46±7.62)染色灰度值明显高于对照组(P〈0.01)。结论大豆蛋白饮食能有效抑制5/6肾切除大鼠的大动脉内膜的MCP-1和LOX-1的表达,提示大豆蛋白饮食有助于减轻慢性肾衰大鼠的早期血管病变。  相似文献   

8.
目的探讨血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)基因转染骨髓间充质干细胞(mesenchymalstemcelis,MSC)对慢性肾衰竭(chronicrenalfailure,CRF)大鼠肾脏的修复作用。方法体外分离、培养大鼠MSC,Ad—VEGF转染MSC。SD大鼠随机分为假手术组(对照组)、慢性肾衰竭模型组(肾衰组)、慢性肾衰竭大鼠MSC移植组(MsC组)、慢性。肾衰竭竭大鼠AdVEGF注射组(VEGF组)和慢性肾衰竭大鼠Ad—VEGF转染的MSC移植组(转染组)。采用分阶段5/6肾切除术制备大鼠CRF动物模型。对照组与肾衰组于切除右肾之前从该侧肾动脉注射不含血清的DMEM培养液,其他3组分别给予MSC、Ad—VEGF和VEGF基因转染的MSC。8周后检测各组大鼠血肌酐(SCr)、血尿素氮(BUN)和24h尿蛋白,观察各组大鼠残肾组织病理形态,并用免疫印迹和RT—PCR方法检测各组大鼠残肾组织VEGFmRNA和蛋白的表达。结果MSC组和转染组SCr、BUN和尿蛋白均较。肾衰组降低(P〈0.05);与MSC组比较,转染组SCr、BUN和尿蛋白降低更明显(P〈0.05)。肾衰组残肾组织VEGFmRNA和蛋白的表达较对照组显著减少(P〈0.05),MSC组和转染组残肾组织VEGFmRNA和蛋白的表达明显增加(与肾衰组比较,均P〈0.05),转染组残肾组织VEGFmRNA和蛋白的表达增加更明显(与M9C组比较,P〈0.05)。结论VEGF基因转染的MSC移植对CRF大鼠的肾脏有修复作用,这可能与VEGF在肾组织中高表达有关。  相似文献   

9.
雷公藤多苷对糖尿病肾病大鼠肾脏中CTGF表达的影响   总被引:5,自引:2,他引:3  
目的:观察糖尿病肾病(DN)大鼠经雷公藤多苷干预后,肾皮质中结缔组织生长因子(connective tissue growth factor,CTGF)表达的变化,并探讨雷公藤多苷在其中的作用。方法:Wister大鼠48只,随机分为正常对照组、DN组与雷公藤多苷治疗组。DN组与雷公藤多苷治疗组大鼠分别给予链脲佐菌素(STZ)55mg/kg一次性腹腔注射建立糖尿病大鼠模型。模型建立后第4、8、12周各组分别处死4只大鼠并收集标本,记录体重、检测血糖、血肌酐、尿素氮、胆固醇、三酰甘油、24h尿蛋白定量。用RT-PCR法检测肾皮质CTGF mRNA含量表达水平。结果:(1)DN组大鼠血糖、血肌酐、血尿素氮、血胆固醇、血三酰甘油、24h尿蛋白定量均明显高于正常对照组(P〈0.01);肾组织CTGFmRNA的表达量明显高于正常对照组(P〈0.01)。(2)雷公藤多苷治疗组血糖、血肌酐、血尿素氮、血胆固醇、血三酰甘油及24h尿蛋白定量在第12周与DN组比较均有统计学差异(P〈0.01);治疗组肾组织CTGFmRNA含量的表达明显低于DN组(P〈0.01)。结论:雷公藤多苷可减少DN大鼠尿蛋白的排泄及降低血尿素氮、血肌酐,明显降低肾组织CTGFmRNA表达量,提示雷公藤多苷能有效延缓DN进展,并有一定的保护作用。  相似文献   

10.
目的观察肾移植受者(Wistar大鼠)应用供者(SD大鼠)抗原特异性CD4^+CD25^+免疫调节性T细胞(CD4^+CD25^+Treg细胞)对移植肾存活时间的影响,为CD4^+CD25^+Treg细胞在体内应用提供定量分析依据。方法SD大鼠为供者,Wistar大鼠为受者,建立同种肾移植动物模型;免疫磁珠(MACS)法分选Wistar大鼠脾脏CD4^+CD25^+T细胞,检测CD4^+CD25^+Foxp3^+T细胞的纯度,并诱导其对SD大鼠供者抗原的特异性表型;根据在肾移植术中经受者尾静脉注射不同数量(2×10^5、5×10^5、1×10^6、2×10^6)的供者抗原特异性CD4^+CD25^+T细胞分为:实验Ⅰ、Ⅱ、Ⅲ、Ⅳ组,并以未注射组作为对照。术后观察移植肾的存活时间;监测血肌酐(cr)的水平;按照BanffSchema标准进行移植肾病理诊断,并根据Watanabe的方法进行半定量评分。结果肾移植术后实验Ⅲ组平均存活时间最长,为(31.4±4.6)d,对照组平均存活时间最短,为(11.7±6.2)d;各实验组与对照组间血Cr检测结果比较,差异均有统计学意义(P〈0.05);实验Ⅲ组和Ⅳ组不同时段的移植肾病理检查半定量评分结果与对照组比较,差异均有统计学意义(P〈0.05)。结论初步证实在受者体内应用适当数量的供者抗原特异性CD4^+CD25^+Treg细胞,能够改善移植肾的功能,有效延长大鼠肾移植术后的存活时间。  相似文献   

11.
Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI2) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI2), TXB2 (stabile metabolite of thromboxane A2) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI2 release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB2 (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI2 release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A2, presumably contributing to hemodynamic stability within 30 min after MT.  相似文献   

12.
Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.  相似文献   

13.
Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.  相似文献   

14.
Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg?1 i. v. and 32 μg · kg?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg?1. The mean ED50s, calculated from dose-response curves, were 5.4 mg · kg?1, 3.9 μg · kg?1 and 0.4 mg · kg?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg?1 and 8 μg · kg?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.  相似文献   

15.
Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg?1 · min?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min?1 · m?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO2I) and oxygen consumption index (VO2I) were also significantly increased in the dopexamine group (DO2I: from 416±91 to 717±110 ml/m2 · m2; VO2I: from 98±25 to 157±22 ml/m2 · m2), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.  相似文献   

16.
A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.  相似文献   

17.
Background: The efficacy of intraoperative salvage and washing of wound blood and the predictors of allogeneic red cell transfusions in prosthetic hip surgery are insufficiently known.
Methods: In 96 patients, undergoing primary or revision surgery, salvaged and washed red cells and, if necessary, allogeneic blood were used to keep haematocrit not lower than 33%. The bleeding of red cells during hospital stay was calculated from the red cell balance. The preoperative red cell reserve (millilitres of red cells in excess of a haematocrit of 33%) was estimated and the difference between this volume and the total bleeding of red cells was retrospectively used to classify patients with regard to the need for red cells. Stepwise regression analysis was used to define patient-related variables associated with allogeneic blood transfusion.
Results: Preoperative knowledge of the type of operation (primary, revision), the preoperative red cell reserve, and the body mass could predict roughly half of the need for banked blood (r2=0.45). Only one-third of the total bleeding of red cells was retransfused. For complete avoidance of allogeneic blood, autotransfusion was most effective in patients with a moderate need (0–4 u). However, 32% of such patients required allogeneic blood.
Conclusions: Autotransfusion has a limited efficacy to decrease the need for allogeneic blood, and other blood-saving methods should be added for this purpose. It is difficult to predict the need for allogeneic blood preoperatively.  相似文献   

18.
目的    观察缺氧对肾小管上皮细胞分泌外泌体的影响,探讨外泌体在缺氧致肾脏损伤中的作用及机制。 方法    (1)常氧(21% O2)及缺氧(1% O2)分别处理大鼠肾小管上皮细胞(NRK-52E)48 h,收集细胞上清液并使用高速梯度离心法分离外泌体。采用透射电镜、纳米示踪分析、Western印迹、蛋白浓度定量鉴定并比较两组外泌体的基本特性。(2)在共培养实验中,以不同浓度(1、10、50、100、300 mg/L)的常氧外泌体、缺氧外泌体分别干预脂多糖(LPS)诱导的大鼠原代腹腔巨噬细胞,使用实时荧光定量PCR与酶联免疫吸附试验(ELISA)法分别检测巨噬细胞白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、诱导型氮氧化物合酶(iNOS)水平;使用Western印迹法检测巨噬细胞磷酸化(p)STAT/STAT及细胞因子信号传导抑制蛋白1(SOCS1)的蛋白表达;最后,使用实时荧光定量PCR法检测常氧外泌体与缺氧外泌体中炎性反应相关微RNA(microRNA,miR)的表达差异。 结果    (1)离心得到的囊泡具有外泌体典型的结构,粒径小于150 nm,表达外泌体标志蛋白CD63,说明分离得到外泌体。缺氧对肾小管上皮细胞分泌的外泌体形态、粒径分布比例无明显影响,但提高了外泌体的分泌量。(2)缺氧外泌体相比于常氧外泌体促进了LPS诱导的M1型巨噬细胞IL-6、TNF-α、iNOS 的表达和分泌(均P<0.01),同时提高STAT的磷酸化水平并减少SOCS1的蛋白表达(均P<0.01);对炎性反应相关microRNA检测发现缺氧外泌体中miR-155、miR-27a表达量较常氧外泌体明显升高(P<0.05)。 结论    缺氧可改变外泌体的生物学功能,表现为协同促进LPS诱导的M1型巨噬细胞的表型转化,这可能是慢性肾脏病微炎性反应状态持续的原因之一。  相似文献   

19.
Abstract While flexible-leaflet, central-flow prosthetic heart valves promise relief from anticoagulation therapy, they continue to be restricted by inadequate durability. In consequence, a novel trileaflet valve, made entirely from polyurethane, has been developed. A batch of 6 consecutively manufactured polyurethane valves was subjected to hydrodynamic function and accelerated fatigue testing. Computerized data acquisition and control systems have been introduced to improve valve testing methodologies. In terms of hydrodynamic function, the polyurethane valve demonstrates transvalvular pressure gradients similar to those for a bioprosthetic valve (Carpentier-Edwards) and levels of retrograde flow significantly less than those for either the bioprosthetic valve or a bileaflet mechanical valve (St Jude Medical). The equivalent of 10 years of cycling without failure has been exceeded by all 6 polyurethane valves in accelerated fatigue tests with 2 valves remaining intact after 674 million cycles (equivalent to approximately 17 years) in continuing tests. Highspeed photography revealed considerable differences in leaflet motion between valves cycled at accelerated and physiological rates.  相似文献   

20.
Background: Ventilation during interventional rigid bronchoscopy (IRB) under general anaesthesia (jet ventilation, positive pressure ventilation and spontaneous assisted ventilation) may offer some difficulties. This study compares the effectiveness during IRB of intermittent negative pressure ventilation (INPV) and spontaneous assisted ventilation (SAV). Methods: Thirty-eight patients submitted to IRB were randomised into two groups: SAV or INPV. All patients received a total intravenous anaesthesia; INPV patients were paralysed. Pre-and intra-operative arterial blood gases and O2 flow through a rigid bronchoscope were assessed. The endoscopist applying a subjective score evaluated the operating conditions. Results: Patients of the INPV group, as compared to the SAV group, required a lower dosage of fentanyl (2.6 ± 1.8 (μg · kg?1· h?1 vs. 6.6 ± 4.8 μg · kg?1· h?1), a lower O2 supply (3.3 ± 2.8 1/min vs. 11.6 ± 3.4 1/min), a shorter recovery time (5.4 ± 2.9 min vs. 9.8 ± 7.1 min) and no manually assisted ventilation (0 ± 0 vs. 1 ± 1.1 nd?/procedure). Intraoperative PaCO2 was higher in the SAV (8.1 ± 1.3 kPa) than in the INPV group (5.0 ± 1.6 kPa) and intraoperative pH differed in the two groups (7.26 ± 0.05, SAV vs. 7.47 ± 0.08, INPV). Operating conditions, as assessed by a subjective score, were considered better with INPV than with SAV (4.9 vs. 4.3). Conclusions: As compared to SAV, INPV in paralysed patients during IRB reduces administration of opioids, shortens recovery time, prevents respiratory acidosis, excludes the need for manually assisted ventilation, reduces 02 need and affords optimal surgical conditions. INPV appears a safe, non-invasive and effective ventilatory management during IRB.  相似文献   

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