硝苯吡啶抑制豚鼠交感神经元的钙依赖性电位

应用细胞内记录技术观察了钙通道阻滞剂硝苯吡啶(nifedlpine)对离体豚鼠腹腔神经节细胞三种钙依赖性电位的可逆性作用。硝苯吡啶(0.1—1mmol/L)可剂量依赖式地抑制动作电位后超极化、强直后膜电位的变化,在无钠高钙加 TEA 溶液中,硝苯吡啶(0.1μmol/L)能抑制钙锋电位。结果表明,大剂量的硝苯吡啶可继发性抑制钙依赖性钾电导,临床治疗剂量的硝苯吡啶还直接减少钙电导。以上作用是硝苯吡啶调节交感节后神经元的兴奋性,阻滞突触前膜 ACh 的量子性释放的基础。     

硝苯吡啶降压作用与血浆中加压激素和降压激素的关系

硝苯吡啶是一种钙通道阻断剂,具有降血压作用。一般认为,硝苯吡啶的降压作用,是由于阻滞血管平滑肌的Ca~(2 )跨膜内流而使血管扩张以及促进肾脏排钠利尿所致。但是硝苯吡啶也能影响包括激素分泌在内的多种钙依赖性生理过程。因此,探讨硝苯吡啶的降压作用与血浆中加压激素和降压激素含量变     

豚鼠主动脉前庭组织的自律性研究和形态学观察

用细胞内微电极技术,对８２只豚鼠主动脉自发电活动进行观察和分析,表明,１６例（１９．５％）出现自律性电活动;６１例（７４．４％）在电刺激诱导下也可出现自律性电活动。进一步观察发现,在主动脉瓣右瓣与后瓣交界以下的局部区域,可记录到有明显４相自动增极化的慢反应自律细胞样的动作电位,并可被钙通道阻滞剂Ｍｎ＾２＋,硝苯吡啶阻断。这一部位之外的其它大部分区域均表现为快反应动作电位,经光镜和电镜观察（ｎ＝１３     

硝苯吡啶对腹腔神经节突触传递的阻断作用

本文应用细胞内记录技术,观察了钙通道阻滞剂硝苯吡啶（nifedipine)对离体豚鼠腹腔神经节突触传递的影响,硝苯吡啶（0.1-10umol/L)不影响所检细胞的静息膜电位,膜电阻及细胞内刺激引起的动作电位,但能显著阻断N-型胆碱能的突触传递,并且这种作用可被低钙模拟、高钙拮抗,硝苯吡啶（10umol/L)也不影响突触后膜对乙酰胆碱（ACh)的敏感性;但在高钾克氏液中,能减少微小兴奋性突触后电位（mEPSPs)的频率;在低钙和高镁克氏液中,能减少量子含量,而对量子大小无影响。结果表明,治疗量的硝苯吡啶(0.1umol/L)通过阻滞突触前膜钙内流及ACh的量子性释放,产生突触阻断作用。这可能是硝苯吡啶降压机理的一个组成部分。     

氨茶碱及硝苯吡啶治疗高原肺水肿效果观察

目的:评价氨茶碱及硝苯吡啶对高原肺水肿的疗效.方法:采用右心漂浮导管方法,观察了静脉推注氨茶碱及舌下含服硝苯吡啶对患者血流动力学及动脉血气等方面的影响.结果:氨茶碱能降低患者的肺动脉压和肺血管阻力,提高患者的心输出量及动脉血氧饱和度,用药前后体循环压及心率未见明显变化.硝苯吡啶含服也能降低肺动脉压和肺血管阻力,虽能降低体循环压但幅度较小,但用药前后心输出量、心率及动脉血气饱和度未见明显变化.结论:氨茶碱及硝苯吡啶均有急性降低高原肺水肿患者肺动脉高压的作用,但二者相比,氨茶碱降低肺动脉压效果明显优于硝苯吡啶.     

硝苯吡啶的药理及其非心血管疾病的临床应用

硝苯吡啶的药理及其非心血管疾病的临床应用张海燕广西南宁市第二人民医院硝苯吡啶系一种钙通道阻滞剂，用以抗心绞痛及抗高血压。但近年来发现此药对多种器官平滑肌均有松驰作用［１］，故临床上除了用于心血管疾病外尚广泛用以治疗消化、呼吸、神经等系统的疾病，并受到...     

输尿管动作电位和蠕动活动的起步点

以往根据离体或除去神经的输尿管以及应用普鲁卡因作脊髓麻醉后,输尿管蠕动不受影响,因此长期以来,输尿管被认为是一自主性器官,其蠕动活动只被尿液牵张刺激所左右。然而近年来大量研究表明,输尿管平滑肌如同心肌和胃肠平滑肌一样,也存在着起步点,整个输尿管的活动为起步点自发产生的动作电位和蠕动活动所控制。尿液机械牵张作用和神经支配虽可影响起步点细胞的活动,但对其自发活动的产生却不是必要的条件。     

输尿管动作电位和蠕动活动的起步点

以往根据离体或除去神经的输尿管以及应用普鲁卡因作脊髓麻醉后,输尿管蠕动不受影响,因此长期以来,输尿管被认为是一自主性器官,其蠕动活动只被尿液牵张刺激所左右。然而近年来大量研究表明,输尿管平滑肌如同心肌和胃肠平滑肌一样,也存在着起步点,整个输尿管的活动为起步点自发产生的动作电位和蠕动活动所控制。尿液机械牵张作用和神经支配虽可影响起步点细胞的活动,但对其自发活动的产生却不是必要的条件。     

川芎嗪,丹参对豚鼠输尿管电位的影响

本工作研究了川芎嗪、丹参对豚鼠输尿管电位的影响。用０．５ｍｇ／ｍｌ、１．０ｍｇ／ｍｌ、２．０ｍｇ／ｍｌ、４．０ｍｇ／ｍｌ的川芎嗪分别注射豚鼠静脉,结果显示对豚鼠输尿管电位有不同的抑制作用。用１：８０、１：４０、１：２０、１：１０的丹参分别注射豚鼠静脉,也对豚鼠输尿管电位有不同的抑制作用。结果表明,丹参具扩张小动脉的作用,川芎嗪、丹参对输尿管平滑肌起了Ｃａ＾２＋的拮抗剂的作用。     

内皮素对豚鼠乳头肌电生理和收缩活动的影响

应用细胞内微电极和肌张力记录技术,观察了ＥＴ－１对豚鼠乳头肌细胞电生理和机械收缩活动的影响。结果表明：ＥＴ－１浓度依赖地明显延长ＰＰＤ和ＡＰＤ９０,增加收肌收缩张力;钾通道阻断剂ＴＥＡ不影响ＥＴ－１的生物效应;而Ｌ型钙通道阻断剂硝苯吡啶、ＥＴＡ受体选择性拮抗剂ＢＱ－１２３和ＡＰⅢ以浓度依赖的方式阻断ＥＴ－１的上述效应,提示ＥＴ－１对乳头肌的电生理和正性肌力效应是由ＥＴＡ受体亚型介导的,与胞浆内Ｃａ     

A method for creating reversible ureteric obstruction in the primate

A technique has been developed for the establishment of a state of reversible, ureteric obstruction in the primate. Ten adult males had baseline ^99mTc-DTPA renogram studies. A randomly selected ureter was totally occluded and obstruction confirmed on renogram. The occlusion was reversed and subsequent renograms confirmed recovery of activity in the obstructed kidneys of the eight animals who survived the reversal procedure. Seven were alive on conclusion of the study. Prevention of ureteric strictures was achieved with an intra-ureteric silastic tube. Autopsies demonstrated patency of every previously occluded ureter. This is the first study to be reported in primates, and the second overall, in which complete ureteric obstruction and its successful reversal has been confirmed on renogram using this surgical method. The technique is suitable for the study of the effect of reversible ureteric obstruction on renal function.     

The absence of a triphasic renovascular response by the multicalyceal kidney of the primate in reaction to acute,complete, unilateral,ureteric obstruction

The early renovascular response by the ipsilateral kidney to acute, total, unilateral, ureteric obstruction was investigated in the adult male chacma baboon (Papio ursinus). Complete occlusion was effected by ligating the ureter at the brim of the bony pelvis (“N” = 10). Sham studies were enacted using the same method but the ureter was not obstructed (“N” = 11). Haemodynamic reactions were monitored for 12 hours. Compared with the sham-occluded set, the renal pelvic pressures in the obstructed group were significantly increased (P < 0.05) from the second hour of the inquiry. However, there were no significant differences in renal blood flow, either between or within the respective cohorts. In this study, the renovascular response to acute ureteric occlusion was similar to that displayed by the multicalyceal kidney of other species under identical conditions. This reaction was fundamentally different to that exhibited by the unicalyceal kidney under similar circumstances.     

TNFRSF13C 在单侧输尿管梗阻大鼠肾组织中的表达及其意义

目的：检测单侧输尿管梗阻（UUO）大鼠肾组织中B 细胞激活因子受体（TNFRSF13C）的表达变化,探讨其在肾间质纤维化 病变中的作用。方法：采用UUO法建立肾间质纤维化大鼠模型,20只成年雄性大鼠,随机分为4组,分别于术后0、3、7、14 天处死 大鼠。取左侧梗阻肾脏进行Masson染色,拍照后,采用双盲法评定各组肾小管间质纤维化程度。提取肾组织中总RNA,用实时荧 光定量聚合酶链反应（RT-PCR）法检测各组肾组织中TNFRSF13C基因表达情况。Pearson 检测TNFRSF13C表达量与肾小管间质 纤维化程度的相关性。结果：随着梗阻时间的延长,肾组织中TNFRSF13C 的mRNA 表达量进行性升高,与肾间质纤维化病变程 度一致,两者呈显著正相关（r=0.915,P<0.01）。结论：TNFRSF13C可能在肾间质纤维化病程中起到了重要作用,并有望成为慢性 肾脏病的临床监测指标。     

苦参素对单侧输尿管梗阻大鼠肾间质纤维化的保护作用

目的探讨苦参素对单侧输尿管梗阻(UUO)大鼠肾间质纤维化的影响及可能机制。方法45只雄性SD大鼠随机分为3组:A假手术组,B单侧输尿管结扎(UUO)组,C治疗组。治疗组在UUO的基础上每天以苦参素100mg/Kg/d腹腔注射。B组和C组于术后第7,14,21,28分别处死5只大鼠,A组于第28天处死大鼠。用PAS及Masson染色法观察肾脏病理改变。用免疫组化法检测转化生长因子β1(transforming growth factor-beta1 TGF-β1),α-平滑肌肌动蛋白(alpha-smooth muscle actin-αSMA),Ⅰ型胶原(collagenⅠColⅠ)的表达。结果与UUO组相比,治疗组梗阻侧肾脏TGF-β1,-αSMA,ColⅠ的表达明显减少,肾小管损害和肾间质纤维化的程度也明显减轻。结论苦参素可通过下调TGF-β1,减少肾小管上皮细胞转分化而减轻肾间质纤维化。     

依帕司他对单侧输尿管梗阻大鼠肾间质纤维化的干预作用及其机制

目的:观察依帕司他(EPS)对单侧输尿管梗阻(UUO)大鼠间质纤维化的保护作用及其机制。方法:实验设假手术组(Sham)组、UUO、UUO+EPS(50 mg/kg)及UUO+EPS(100 mg/kg)剂量组,每组n=8。左侧输尿管结扎制备UUO大鼠模型。造模后连续灌胃给药3周,sham和UUO组给予等体积的羟甲基纤维素钠。HE和Masson染色观察肾组织病理变化及胶原沉积情况。免疫组化法观察肾组织醛糖还原酶(AR)表达情况,分别采用real-time PCR和(或) Western blot检测肾脏I型胶原(collagen I)、III型胶原(collagen III)、α-平滑肌肌动蛋白(α-SMA)、成纤维细胞特异蛋白-1(FSP-1)、纤连蛋白(FN)、E-钙粘蛋白(E-cadherin)、转化生成因子-β1(TGF-β1)和AR mRNA及蛋白表达。结果:与Sham组相比,UUO组大鼠小管上皮细胞萎缩、空泡样变性,肾间质成纤维细胞及肌成纤维细胞大量增殖并伴大量炎症细胞浸润,胶原沉积明显增加,collagen I、collagen III、TGF-β1和AR mRNA及蛋白表达水平明显升高(P<0.01),同时EMT标志性蛋白α-SMA、FSP-1、FN mRNA及蛋白表达水平明显升高(P<0.01),而E-cadherin mRNA及蛋白表达水平明显降低。与UUO组相比,经EPS治疗3周后,肾间质纤维化程度明显减轻,胶原沉积明显减少,collagen I、collagen III、TGF-β1和AR mRNA及蛋白表达水平明显降低(P<0.01或P<0.05),另外α-SMA、FSP-1、FN mRNA及蛋白表达水平明显降低(P<0.01或P<0.05),而E-cadherin mRNA及蛋白表达水平明显升高(P<0.01或P<0.05),而且100 mg/kg剂量组上述指标的改变均好于低剂量组(P<0.05,P<0.01)。结论:依帕司他对肾间质纤维化具有一定的改善作用,其机制可能与其抑制TGF-β1介导的AR表达、进而抑制大鼠肾小管上皮细胞EMT有关。     

依那普利在大鼠单侧输尿管梗阻再通模型中的抗纤维化作用

目的:探讨依那普利对大鼠单侧输尿管梗阻再通模型肾脏纤维化的影响.方法:18只SD大鼠随机分为两组:假手术组(6只)以及单侧输尿管梗阻模型组(12只).输尿管梗阻3天后,实施梗阻再通手术,再将大鼠随机分为模型组(6只)以及依那普利组(6只),术后,依那普利组给予依那普利灌胃10mg/kg/d,假手术组以及模型组给予等量0.5%CM-CNa溶液灌胃.用药2周后,取术侧肾组织做HE染色,并采用Raford评分系统对肾间质损伤程度进行评分;用Real-timePCR方法检测Ⅰ、Ⅲ型胶原以及CT-GFmRNA的表达;用Westemblot方法检测CTGF蛋白水平的表达.结果:模型组大鼠肾脏损伤程度,Ⅰ、Ⅲ型胶原mRNA表达水平,以及CTGFmRNA和蛋白表达水平均比假手术组明显上升(P<0.01).经依那普利治疗后,与模型组相比,以上指标均显著下降(P<0.01).结论:依那普利能有效阻止大鼠单侧输尿管梗阻再通后肾脏纤维化的进展.依那普利抗纤维化的作用机制可能与抑制CTGF的表达有关.     

甲磺酸伊马替尼对单侧输尿管梗阻小鼠肾间质纤维化的保护作用

目的研究甲磺酸伊马替尼（STI571）改善单侧输尿管梗阻（UUO）小鼠肾间质纤维化的作用及机制。方法48只小鼠随机分为4组：假手术组,模型组,小剂量治疗组（80mg/kg/d）,大剂量治疗组（160mg/kg/d）。采用左侧输尿管双结扎的方法建立UUO模型,治疗组每天以STI57180、160mg/Kg灌胃。分别于术后第8,11d分别处死各组小鼠6只。光镜下观察肾脏病理改变。用免疫组化技术检测肾组织TGF-β1、PAI-1、α-SMA和PCNA的表达。结果治疗组的肾间质纤维化定量显著低于模型组（P〈0.05）,且不同剂量组之间存在显著差异（P〈0.05）。模型组和治疗组左肾TGF-β1、PAI-1、α-SMA和PCNA的表达均随梗阻时间延长而逐渐增加,治疗组α-SMA和PCNA的表达较模型组明显减低（P〈0.05）。结论甲磺酸伊马替尼可显著减轻UUO小鼠梗阻侧肾脏间质纤维化,下调α-SMA和PCNA的表达,减少肾间质细胞外基质的沉积,对UUO小鼠肾间质纤维化有一定防治作用。     

Bone marrow mesenchymal stem cells reduce ureteral stricture formation in a rat model via the paracrine effect of extracellular vesicles

With no effective therapy to prevent or treat ureteral stricture (US), a multifactorial fibrotic disease after iatrogenic injury of the ureter, the need for new therapies is urgent. Mesenchymal stem cells (MSCs) have been widely studied for treating tissue defects and excessive fibrosis, and recent studies established that one of the main therapeutic vectors of MSCs is comprised in their secretome and represented by extracellular vesicles (EVs). Thus, we have determined to explore the specific role of MSCs‐derived EVs (MSC‐EVs) treatment in a pre‐clinical model of US. The results firstly showed that either a bolus dose of MSCs or a bolus dose of MSC‐EVs (administration via renal‐arterial) significantly ameliorated ureteral fibrosis and recuperated ureter morphological development in a US rat model. We confirmed our observations through MSCs or MSC‐EVs treatment alleviated hydronephrosis, less renal dysfunction and blunted transforming growth factor‐β1 induced fibration. Due to MSC‐EVs are the equivalent dose of MSCs, and similar curative effects of transplantation of MSCs and MSC‐EVs were observed, we speculated the curative effect of MSCs in treating US might on account of the release of EVs through paracrine mechanisms. Our study demonstrated an innovative strategy to counteract ureteral stricture formation in a rat model of US.     

ATP synthase of yeast: structural insight into the different inhibitory potencies of two regulatory peptides and identification of a new potential regulator

Quantitative and qualitative alterations of renal oversulfated chondroitin/dermatan sulfates (C/DSs) accompanied by the development of tubulointerstitial nephritis were examined. The rat model with unilateral ureteral obstruction (UUO) is a suitable model for study of renal interstitial fibrosis, and was utilized in the present study. Cortical regions of serial sections of UUO kidney and sham-operated kidney on glass slides were processed using a small surgical knife under dark field microscopy. Oversulfated C/DSs in tissue sections on a glass slide were degraded to unsaturated disaccharides using chondroitinase ABC and ACII digestion in the presence of bacterial collagenase. The resulting unsaturated disaccharides were subsequently determined by HPLC. These in situ investigations yielded the following results: (1) marked increases in oversulfated C/DSs content and decreases in the oversulfation degree of C/DSs were observed in fibrous lesions, compared to non-fibrous lesions, and (2) iduronic acid content in C/DSs in fibrous lesions was significantly lower than that in non-fibrous lesions. These findings indicate that oversulfated C/DSs with low-iduronic acid content represent a potential marker for tubulointerstitial nephritis.     

波形蛋白在实验性肾间质纤维化上皮-间充质转分化中的表达及意义

目的明确肾脏纤维化中波形蛋白表达在上皮-间充质转分化观察中的意义。方法雄性SD大鼠12只,随机分成假手术组和模型组,模型组行单侧输尿管梗阻术。造模后14天处死大鼠,分别采用免疫组织化学染色和Western印迹法对梗阻侧肾组织波形蛋白和α平滑肌肌动蛋白作定性和定量检测。并通过体外实验用TGF-β1刺激诱导人近端小管上皮细胞株(HK-2)发生上皮-间充质转分化。采用间接免疫荧光法对E-钙粘蛋白和波形蛋白进行染色,采用激光共聚焦显微镜观察细胞形态改变,并用蛋白印迹法定量检测HK-2细胞波形蛋白和α平滑肌肌动蛋白表达水平。结果萎缩和扩张的肾小管上皮细胞出现波形蛋白和α平滑肌肌动蛋白表达,肾组织中波形蛋白和α平滑肌肌动蛋白表达量显著增加;正常的HK-2细胞,细胞形态为不规则圆形,TGF-β1刺激后细胞伸展成长梭形;细胞α平滑肌肌动蛋白表达水平显著增加,波形蛋白表达水平无显著变化。结论体内实验研究上皮-间充质转分化,将波形蛋白作为间充质细胞标志物具有较好的参考价值,而体外研究中,其标志作用尚存在争议。