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1.
顾勇  陈靖 《中华消化杂志》1998,18(2):105-107
目的 观察肝硬化大鼠AVP系统的变化及中药黄芪的治疗作用。方法 采用斑点杂交和半定量RT-PCR法检测胆总管结扎2周所致肝硬化大鼠下丘脑AVP及其肾脏皮质V1a受体基因表达。结果 肝硬化大鼠下丘脑AVPmRNA水平明显升高,肾脏皮质V1a受体mRNA表达下调,可能与非渗透性因素有关。应用黄芪可使模型鼠AVP高表达下降,并促使肾脏皮质V1a受丛基因表达进一步降低。结论 肝硬化大鼠存在AVP系统异常,  相似文献   

2.
目的 探讨尾加压素Ⅱ(UrotensinⅡ,UⅡ)及其受体(GPR14)在单侧输尿管梗阻(UUO)大鼠肾间质中的表达及意义.方法 将24只雄性Wistar大鼠随机分为假手术组(Sham组)及模型组(UUO组),采用左侧输尿管结扎术复制UUO模型.术后第14和28天分别处死两组大鼠,取左肾进行HE和Masson染色,并用免疫组化检测肾间质中UⅡ和GPR14的表达,RT-PCR检测UⅡ和GPR14 mRNA表达.结果 HE和Masson染色显示模型组大鼠肾小管间质增宽,炎细胞浸润,纤维组织增多,随时间进展病变更加明显(P<0.01);免疫组化显示UUO组2 w时肾间质UⅡ及GPR14表达明显增多,与Sham组比较差异显著(P<0.01);UUO组4 w时UⅡ及GPR14持续高表达(P<0.01).RT-PCR显示2 w后,与Sham组比较,UUO组大鼠肾组织中UⅡmRNA表达明显增加(P<0.01),GPR14表达也有增加趋势,但无显著差异性;4 w后UUO组UⅡmRNA表达仍明显高于Sham组(P<0.01),GPR14表达也明显升高(P<0.01).结论 UⅡ及GPR14 的蛋白表达和mRNA水平在UUO大鼠肾间质中明显增加,提示UⅡ的表达与肾纤维化有关,可能参与了肾纤维化的过程.  相似文献   

3.
目的:研究下丘脑精氨酸血管加压素( A V P) 和其 V2 受体与 A V P 依赖性水通道水孔蛋白2( A Q P2 )在阿霉素肾病综合征大鼠肾脏表达的情况,及中药黄芪对此的影响。 方法:下丘脑 A V P m R N A 检测用斑点杂交法,肾脏皮髓质 A V P V2 受体、 A Q P2 m R N A 检测采用半定量 R T P C R 法。 结果:肾病大鼠下丘脑 A V Pm R N A表达较正常对照增强( A:5359 ±549 vs 2572 ±196 , P< 001) ,黄芪可纠正此种高表达( A:2188 ±125) 。半定量 R T P C R 检查发现肾脏皮质和髓质 V2 受体、 A Q P2 m R N A 表达均呈现有意义的上调,黄芪则可使这些变化缓解( P 均< 001) 。 结论:在阿霉素肾病大鼠中存在下丘脑 A V P 基因表达的增加,肾脏 A V P V2 受体和 A Q P2m R N A 表达的上调,这些变化可能是肾病水潴留的机制之一,中药黄芪能改善这些变化。  相似文献   

4.
目的 研究小窝蛋白-1反义寡核苷酸(cav1-AS ODN)在血管加压素(AVP)诱导的成年大鼠心肌成纤维细胞(CFs)增殖erk1/2信号转导中的作用及辛伐他汀(Sim)对cav1表达的干预效应.方法 采用脂质体导入法将cav1-AS ODN导入离体培养的成年大鼠CFs,用3H-TdR掺入法定量观察CFs增殖,蛋白免疫印迹法分析cav1-AS ODN对AVP诱导大鼠CFs增殖后磷酸化erk1/2 (p-erk1/2)、p21和细胞周期蛋白A(cyclin A)表达变化及Sim对cav1表达的影响.结果 cav1-AS ODN与10-7 mol/L的AVP共同干预组,大鼠CFs内3H-TdR掺入率和p-erk1/2蛋白表达量分别相当于空白对照组的(212±6)% 和(7.9 ± 0.3)%,10-7mol/L的AVP单独干预组的3H-TdR掺入率和p-erk1/2表达量分别相当于空白对照组的(172±4)%和(5.7±0.2)%,两组比较差异非常显著(P<0.01).cav1-AS ODN单独干预或与10-7mol/L的AVP共同干预大鼠CFs 24 h后,两组CFs内p21表达丰度均较空白对照组下降,cyclin A表达丰度升高.β-环糊精、黄体酮或Sim可减少CFs胞膜上cav1蛋白表达.用10、15或20 μg/ml胆固醇分别与10-7 mol/L Sim共同干预CFs 24 h后,CFs胞膜上cav1蛋白表达量分别相当于对照组的(86±3)%、(91±4)%和(94±5)%,与10-7mol/L Sim单独作用CFs组(66±4)%比较,均有显著的统计学差异(P<0.05,P<0.01).结论 cav1-AS ODN可增强AVP促CFs增殖的作用,Sim降胆固醇作用影响CFs胞膜上cav1蛋白表达,从而影响CFs增殖.  相似文献   

5.
背景和目的 水孔蛋白2(AQP2)是调节机体水平衡的通道蛋白,与多种具水盐代谢异常疾病的病理发生发展密切相关,本文观察血管加压素(AVP)对wKY大鼠肾脏AQP2表达的影响.方法 WKY大鼠16只,随机分成2组,一组AVP[2.5 U/(kg·d)]腹腔注射,等量的生理盐水腹腔注射为对照.7天后处死大鼠,RT-PCR法检测两组大鼠肾脏AQP2的mRNA表达,免疫组化法检测AQP2蛋白表达水平,放射免疫法检测大鼠血浆AVP浓度.结果 AVP注射组大鼠血浆AVP浓度明显升高[(65.7±7.9)vs对照组(51.2±7.9)pg/mL,P<0.05],肾脏AQP2 mRNA(0.68±O.14 vs O.39±O.11,P<0.05)和AQP2蛋白表达水平(O.71±O.09 vs O.42±O.12,P<0.05)均显著高于对照组.结论 AVP可刺激肾脏AQP2的表达,AQP2可能是AVP调节肾脏水代谢的机制之一.提示水通道蛋白2表达的调节可能成为干预某些心血管疾病,如充血性心力衰竭、高血压的靶点.  相似文献   

6.
目的观察黄芪多糖(APS)对糖尿病(DM)大鼠尿量、肾脏水通道蛋白-2(AQP-2)表达和肾脏超微结构的影响及其治疗DM的机制。方法腹腔注射链脲佐菌素(STZ)制备DM大鼠模型,实验分4组:正常组、DM组、APS低和高剂量组,实验持续6w。采用免疫荧光检测各组大鼠肾脏AQP-2的表达,电镜观察各组大鼠肾脏超微结构,简易代谢笼法测各组大鼠24h尿量,并测定大鼠肾重/体重、尿微量白蛋白(UAER)排泄率及内生肌酐清除率(Ccr)等。结果 DM组大鼠肾脏髓质AQP-2表达较正常组明显增多,APS可抑制DM大鼠肾脏AQP-2表达。DM组大鼠肾脏超微结构呈明显退行性变,APS干预可改善其超微结构。DM组大鼠尿量明显高于正常组(P0.01),APS可增加DM大鼠尿量(P0.01)。APS低剂量组和高剂量组大鼠UAER、Ccr、肾重/体重低于DM组(P0.01)。结论 APS下调肾髓质AQP-2过度表达,缓解DM水钠潴留,保护肾脏。  相似文献   

7.
血管加压素在脑水肿形成中的作用   总被引:1,自引:0,他引:1  
血管加压素(VP)的作用可分为外周和中枢2个部分,涉及到水的重吸收、血管收缩、促肾上腺皮质激素的分泌和记忆等重要生理作用。其受体分为V1aR、V1bR和V2R,中枢神经系统中以V1R为主。在脑外伤、脑出血和脑梗死等病理学过程中,VP常常异常增高,增加脑含水量,加重脑水肿。实验证明,V1aR在VP介导的脑水肿形成中起重要作用,但具体机制尚须进一步明确。研究VP在脑水肿形成过程中的病理生理学作用,对脑水肿的治疗有重要的指导意义。  相似文献   

8.
目的 探讨两肾一夹(2K1C)高血压大鼠肾脏血管紧张素转换酶2(ACE2)表达.了解甘肃黄芪对大鼠肾脏ACE2 mRNA表达及血浆血管紧张素Ⅱ(AngⅡ)的影响,观察黄芪的降压效果.方法 50只雄性Wistar大鼠随机分为5组:正常对照组(n=10);2K1C高血压组(n=10);2K1C 缬沙坦组(n=10);2K1C 黄芪20 g/(kg·d)组(n=10);2K1C 黄芪10 g/(kg·d)组(n=10).8周后,用RT-PCR法检测肾脏ACE2 mRNA表达,免疫组化法检测肾脏ACE2表达,放射免疫分析法测定肾脏局部AngⅡ水平.结果 2K1C高血压大鼠肾脏ACE2 mRNA表达较正常大鼠降低(0.282±0.025 vs 0.359±0.017,P<0.05),高、低剂量黄芪及缬沙坦治疗大鼠ACE2 mmRNA表达(0.398±0.004,0.391±0.006,0.403±0.009)均高于对照组(0.282±0.025)(P<0.05).高剂量黄芪组降低肾脏局部AngⅡ效果较缬沙坦组明显(P<0.01).缬沙坦和黄芪治疗都明显降低血压(P<0.01).结论 2K1C高血压大鼠肾脏组织中ACE2 mRNA表达降低.甘肃黄芪及缬沙坦在降压的同时增加肾脏组织ACE2 mRNA表达.  相似文献   

9.
目的探讨两肾一夹(2K1C)高血压大鼠肾脏血管紧张素转换酶2(ACE2)表达。了解甘肃黄芪对大鼠肾脏ACE2mRNA表达及血浆血管紧张素Ⅱ(AngⅡ)的影响,观察黄芪的降压效果。方法50只雄性Wistar大鼠随机分为5组:正常对照组(n=10);2K1C高血压组(n=10);2K1C+缬沙坦组(n=10);2K1C+黄芪20g/(kg.d)组(n=10);2K1C+黄芪10g/(kg.d)组(n=10)。8周后,用RT-PCR法检测肾脏ACE2mRNA表达,免疫组化法检测肾脏ACE2表达,放射免疫分析法测定肾脏局部AngⅡ水平。结果2K1C高血压大鼠肾脏ACE2mRNA表达较正常大鼠降低(0.282±0.025vs0.359±0.017,P<0.05),高、低剂量黄芪及缬沙坦治疗大鼠ACE2mRNA表达(0.398±0.004,0.391±0.006,0.403±0.009)均高于对照组(0.282±0.025)(P<0.05)。高剂量黄芪组降低肾脏局部AngⅡ效果较缬沙坦组明显(P<0.01)。缬沙坦和黄芪治疗都明显降低血压(P<0.01)。结论2K1C高血压大鼠肾脏组织中ACE2mRNA表达降低。甘肃黄芪及缬沙坦在降压的同时增加肾脏组织ACE2mRNA表达。  相似文献   

10.
背景和目的水孔蛋白2(AQP2)是调节机体水平衡的通道蛋白,与多种具水盐代谢异常疾病的病理发生发展密切相关,本文观察血管加压素(AVP)对 WKY 大鼠肾脏 AQP2表达的影响。方法 WKY 大鼠16只,随机分成2组,一组 AVP[2.5 U/(kg·d)]腹腔注射,等量的生理盐水腹腔注射为对照。7天后处死大鼠,RT-PCR法检测两组大鼠。肾脏 AQP2的 mRNA 表达,免疫组化法检测 AQP2蛋白表达水平,放射免疫法检测大鼠血浆 AVP浓度。结果 AVP 注射组大鼠血浆 AVP 浓度明显升高[(65.7±7.9)vs 对照组(51.2±7.9)pg/mL,P<0.05],肾脏 AQP2 mRNA(0.68±0.14 vs 0.39±0.11,P<0.05)和 AQP2蛋白表达水平(0.71±0.09 vs 0.42±0.12,P<0.05)均显著高于对照组。结论 AVP 可刺激肾脏 AQP2的表达,AQP2可能是 AVP 调节肾脏水代谢的机制之一。提示水通道蛋白2表达的调节可能成为干预某些心血管疾病,如充血性心力衰竭、高血压的靶点。  相似文献   

11.
AIM: Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. We have found inducible nitric oxide synthase (iNOS) can be induced in hepatocytes of cirrhotic liver. This study further investigated the temporal expression and activity of hepatic iNOS in cirrhosis development. METHODS: Cirrhosis was induced in rats by chronic bile duet ligatjon (BDL). At different time points after the operation, samples were collected to examine NO concentration, liver function, and morphological changes. Hepatocytes were isolated for determination of iNOS mRNA, protein and enzymatic activity. RESULTS: Histological examination showed early cirrhosis 1-2 wk after BDL, with advanced cirrhosis at 3-4 wk. Bilirubin increased dramatically 3 d after BDL, but decreased by 47% on d 14. Three weeks after BDL, it elevated again. Systemic NO concentration did not increase significantly until 4 wk after BDL, when ascites developed. Hepatocyte iNOS mRNA expression was identified 3 d after BDL, and enhanced with time to 3 wk, but reduced thereafter. iNOS protein showed a similar pattern to mRNA expression. iNOS activity decreased from d 3 to d 7, but increased again thereafter till d 21. CONCLUSION: Hepatic iNOS can be induced in the early stage, which increases with time as cirrhosis develops. lts enzymatic activity is significantly correlated with protein expression and histological alterations of the liver, but not with systemic NO levels, nor with absolute values of liver function markers.  相似文献   

12.
AIM: To assess the effects of obstructive cholestasis on a wider range of gene expression using microarray technology. METHODS: Male C57BL/6J mice underwent common bile duct ligation (BDL) and were matched with pair-fed sham-operated controls. After 7 d,the animals were sacrificed and total RNA was isolated from livers and kidneys. Equal amounts of RNA from each tissue were pooled for each group and hybridized to Affymetrix GeneChip(?)MG-U74Av2 containing a total of 12488 probe sets. Data analysis was performed using GeneSpring(?) 6.0 software. Northern analysis and immunofluorescence were used for validation. RESULTS: In sham-operated and BDL mice, 44 and 50% of 12488 genes were expressed in livers, whereas 49 and 51% were expressed in kidneys, respectively. Seven days after BDL, 265 liver and 112 kidney genes with GeneOntology annotation were up-regulated and 113 liver and 36 kidney genes were down-regulated in comparison with sham-operated controls. Many genes were commonly regulated in both tissues and metabolism-related genes represented the largest functional group. CONCLUSION: Following BDL, microarray analysis reveals a broad range of gene alterations in both liver and kidney.  相似文献   

13.
目的 研究胆管上皮细胞(biliary epithelia cells,BECs)增生在胆管结扎(bile duct ligation,BDL)大鼠胆汁性肝纤维化形成中的作用.方法 BDL的方法制作大鼠胆汁性肝纤维化模型,5周后杀鼠取材,观察内容包括大鼠血清总胆红素(TBlL)、总胆汁酸(TBA),肝组织羟脯氨酸(Hyp)含量,组织病理学,免疫组织化学观测Ⅰ型胶原(Col Ⅰ)、Ⅳ型胶原(Col Ⅳ)、层粘蛋白(LN)、纤连蛋白(FN)和α-平滑肌肌动蛋白(α-SMA);肝组织片激光显微切割(LCM)获取BECs,实时荧光定量PCR检测BECs表达Procollagen α1(Ⅳ)、血小板衍生生长因子B(PDGF-B)、结缔组织生长因子(CTGF)及转化生长因子β1(TGF-β1)mRNA.结果 1、胆管结扎模型大鼠血清TBiL和TBA含量均值分别为假手术组大鼠的22倍和3倍(P<0.01);模型组大鼠肝组织Hyp含量是假手术组的4倍(P<0.01);2、模型组大鼠BECs增生非常显著,肝实质细胞比例显著减少;3、模型组大鼠在增生胆管周围的LM表达显著增加;FN不但在肝窦内有阳性染色,还强烈地表达于增生的胆管周围;肝窦壁的Col Ⅰ阳性染色增强,增殖的BECs周围未见明显阳性染色;肝窦壁ColⅣ表达未见明显变化,但强烈表达于增殖的BECs周围的基底膜上;α-SMA阳性染色见于汇管区周围的肌成纤维细胞上,且这些肌成纤维细胞常常围绕在增生的胆管上皮细胞周围.4、模型组大鼠BECs的Procol α1(Ⅳ)、PDGF-B、TGF-β1及CTGF的mRNA表达量均显著增加(与假手术组比较,均为P<0.001).结论 BECs增生是BDL大鼠胆汁性肝纤维化的启动因素和中心病理环节,抑制胆管上皮细胞的异常增生及其细胞生物学病理变化应是抗胆汁性肝纤维化治疗学研究的主要目标.  相似文献   

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15.
INTRODUCTIONObstruction of bile ? ow through the extrahepatic biliary system results in development of oxidant injury, hepatic fibrosis, biliary cirrhosis, and portal hypertension[1,2]. Patients with obstructive jaundice are at significant risk for severe…  相似文献   

16.
目的 探讨肝硬化患者尿液中水通道蛋白 2 (AQP 2 )含量变化与水代谢紊乱的关系。方法 应用放射免疫分析法测定 3 2例肝硬化患者和 10例健康志愿者尿液中AQP_2的浓度以及血浆血管加压素 (P_AVP)浓度 ,用冰点抑制法测定每位受试者尿渗量和血浆渗量 ,以计算自由水清除率。结果 和健康志愿者相比 ,肝硬化患者尿液中AQP_2浓度和P_AVP浓度均明显升高 (分别为12 .9± 3 .7vs 2 .8± 2 .3和 1.2 3± 0 .93vs 0 .71± 0 .5 3P <0 .0 5 ) ,并且尿AQP_2含量随肝功能Child_pugh分级加重而升高 ( 4 .70± 2 .5 7vs 10 .0 8± 4.5 2vs 2 3 .96± 7.5 9P <0 .0 5 ) ;尿AQP_2浓度与自由水清除率呈负相关 (r =-0 .62P <0 .0 1)。结论 肝硬化患者尿AQP_2浓度明显升高 ,并随肝硬化严重程度加重而升高 ,与自由水清除率呈负相关 ,提示AQP_2在肝硬化患者水代谢紊乱方面发挥重要作用  相似文献   

17.
The genesis and development of tumor are closely connected with immune system and neuroendocrine system. To investigate the changes of neuroendocrine and immune system in leukemia patients and their probable connection with leukemia, we studied five groups of patients including leukemia patients with normal temperature, leukemia patients with high temperature and infection (high-leukocyte count group and low leukocyte count group), general patients with fever and healthy Chinese adult blood donors as control group. We determined their blood cell counts by blood count meter, determined their arginine vasopressin (AVP) levels in blood plasma by radioimmunoassay and their cross-reacting protein (CRP), and lipopolysaccharide (LPS) levels by immunoturbidimetry. Then we studied the difference and association among these indexes. Our results revealed a significant increase of AVP, LPS, and CRP levels in the blood of leukemia patients with normal temperature vs. normal people; Individual leukemia patients had high AVP levels although they had normal LPS and CRP levels; In the group of leukemia patients with high temperature and low leukocyte counts, the CRP level is significantly higher than some of other groups, while there was no significant increase in its AVP level. We conclude that no matter the temperature is normal or not, there were always neuroendocrine disturbance, inflammation, and inapparent infection in leukemia patient; To the leukemia patients with low leukocyte counts, the relationship between inflammation and neuroendocrine is more complicated.  相似文献   

18.
目的根据MRI T1值和T2值,计算肝细胞外体积分数(extracellular volume,ECV),借此评估ECV值在肝纤维化诊断和分级中的价值。方法通过胆管结扎(bile duct ligation,BDL)和四氯化碳(CCl 4)诱导90只雄性Sprague-Dawley大鼠肝脏不同程度的纤维化,并且侵入性地测量门静脉压力。测定羟脯氨酸含量、天狼星红染色和平滑肌肌动蛋白染色对肝纤维化进行定量。使用定量MRI映射技术评估T1值、T2值和ECV值。结果BDL 4周组T1值高于假手术组[(723±68)msec vs(583±30)msec,P<0.001];T2值也高于假手术组[(45±3)msec vs(27±3)msec,P<0.001]。在CCl 4动物模型中观察到相似的T1和T2值的变化。BDL 4周组与假手术组相比,ECV值更高[(31.5±1.5)%vs(18.7±3.1)%,P<0.001],CCl 4动物模型中结果相似。ECV值与肝羟脯氨酸含量(BDL:r=0.65,P<0.001;CCl 4:r=0.63,P<0.001)、天狼星红染色(BDL:r=0.85,P<0.001;CCl 4:r=0.81,P<0.001)、平滑肌肌动蛋白染色(BDL:r=0.73,P<0.001;CCl 4:r=0.72,P<0.001)和门静脉压力(BDL:r=0.57,P=0.006;CCl 4:r=0.35,P=0.047)、Ⅰ型胶原蛋白有高度相关性。结论实验动物模型T1值、T2值和ECV值的升高与肝纤维化和门静脉高压的严重程度有关。  相似文献   

19.
研究精氨酸血管加压素(AVP)对小鼠成骨细胞增殖和分化的影响及作用机制。(1)原代分离的小鼠成骨细胞中,加入100 nmol/ L 的 AVP 培养72 h 后检测其对成骨细胞增殖作用的影响。(2)培养2、4、6、8、10 d 收集细胞培养液,并收集培养第10天的细胞裂解液,检测 AVP 对碱性磷酸酶(ALP)分泌的动态影响及细胞内 ALP 含量变化。(3)利用茜素红染色法检测 AVP 对培养8 d 和20 d 的成骨细胞形成钙结节的影响。(4)AVP 作用20 min,裂解细胞,利用放免法检测 AVP 对成骨细胞内 cAMP 的影响。结果显示,与对照组相比较,100 nmol/ L 能够促进小鼠原代成骨细胞增殖(P<0.01)。 AVP 能够使 ALP 的分泌量随着时间推移有显著增加(P<0.01);并增加成骨细胞形成钙结节数量和面积(P<0.01)。同时 AVP 能够促进胞内 cAMP 水平的增加(P<0.01)。结果提示 AVP 可能通过 cAMP 信号通路促进小鼠成骨细胞的增殖与分化。  相似文献   

20.
AIM: To investigate the role of heme oxygenase-1 (HO-1) in pathogenesis of experimental hepatorenal syndrome (HRS). METHODS: Rats were divided into liver cirrhotic group, zinc protoporphyrin IX (ZnPP) treatment group, cobalt protoporphyrin (CoPP) treatment group and sham group. Biliary cirrhosis was established by bile duct ligation in the first three groups. Rats in the ZnPP and CoPP treatment groups received intraperitoneal injection of ZnPP and CoPP, respectively, 24 h before sample collection. Expressio...  相似文献   

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