清胰汤、红霉素对急性胰腺炎大鼠肠动力的影响

目的 探讨清胰汤及红霉素对大鼠急性胰腺炎（AP）肠动力的影响。方法 对胆总管逆行注射牛磺胆酸钠诱导大鼠AP，随后灌服清胰汤和红霉素，并设对照组进行比较。结果 AP组较对照组小肠推进比明显减低，清胰汤组和红霉素组大鼠的小肠推进比较AP组明显提高，清胰汤组的胰腺组织病理改变和血清淀粉酶显改善。结论 清胰汤和红霉素都能改善AP大鼠的胃肠动力，防止并发症的发生，清胰汤的综合效应优于红霉素。     

脂多糖对离体大鼠胰腺腺泡细胞钙稳态的影响

目的:研究脂多糖(LPS)对胰腺腺泡细胞钙稳态的影响,及胞浆内钙超载时钙离子的来源,以探讨LPS致胰腺腺泡细胞损伤的机制。方法:胶原酶法分离胰腺腺泡细胞,Fluo-3/AM负载后,在无钙或含生理钙离子浓度的培养液中加入不同浓度LPS,采用激光共聚焦显微镜观察单个胰腺腺泡细胞[Ca~(2+)]_i。另外采用MTT法检测LPS作用的不同时间点胰腺腺泡细胞的活性。结果:LPS可致胰腺腺泡细胞损伤、细胞内[Ca~(2+)]_i显著升高,且呈浓度依赖性(P<0.05):在含1mmol/L依他酸的培养液中,LPS致腺泡细胞损伤程度明显减轻(P<0.05)、仅引起胰腺腺泡细胞[Ca~(2+)]_i缓慢、微弱的升高,而再次恢复培养液中Ca~(2+)至生理浓度,引发快速、幅度更高而持久的[Ca~(2+)]_i变化。腺泡细胞内[Ca~(2+)]_i的变化明显先于腺泡细胞的损伤。结论:LPS导致胰腺腺泡细胞内钙超载,主要源于胞外Ca~(2+)内流。钙超载作为早期的病理事件参与腺泡细胞损伤的发生,钙稳态失衡是LPS致胰腺细胞损伤的主要因素之一。     

L-型钙通道阻滞剂对心肌细胞钙稳态的影响

目的观察L-型钙通道阻滞对心肌细胞的影响。方法取SD大鼠颈部脱臼处死后浸入75%乙醇数秒,迅速开胸摘取心脏,置入盛有37℃预热的台氏液100ml的培养皿中。在超净工作台上用台式液清洗并修剪掉结缔组织,迅速行主动脉插管。将心脏悬挂于Langendroff灌流装置上,剪下心室并剪成约1mm3的组织块,放入37℃预热的含0.2mmol/L Ca2＋台氏液20ml的培养皿中,将心室在溶液中轻轻晃动以分散已解离的心室肌细胞。新分离的细胞在常温下放置1～2h后,用加样器取带少许细胞的原液放入试管中,加入指示剂,给予正常细胞外液灌流,测全细胞胞内钙瞬变作为前对照组;给予硝苯地平溶液灌流,测全细胞胞内钙瞬变作为实验组;给予正常细胞外液灌流,测全细胞胞内钙瞬变作为后对照组。结果不同浓度的硝苯地平对静息状态下心室肌细胞胞内钙信号的影响都不明显,仅10μmol/L硝苯地平可能使静息状态下心室肌细胞胞内钙水平轻微降低,更高浓度的硝苯地平的效果反而减弱。不同浓度的硝苯地平都能不同程度降低心室肌细胞胞内钙瞬变的峰值（P〈0.05）,5μmol/L硝苯地平的标准化值最低,降低心室肌细胞胞内钙瞬变峰值的效果比2μmol/L硝苯地平明显（P〈0.05）。但是10μmol/L硝苯地平、50μmol/L的硝苯地平的降低心室肌细胞胞内钙瞬变峰值的效果反而减弱。结论硝苯地平可以抑制大鼠心室肌细胞的电流。但是,硝苯地平对于静息状态下的心室肌细胞胞内钙信号的影响不明显,可能与硝苯地平只对去极化过程的ICa2＋、Ito和IK有抑制作用有关。     

L-型钙通道阻滞剂对心肌细胞钙稳态的影响

目的:观察L-型钙通道阻滞对心肌细胞的影响.方法:取SD大鼠颈部脱臼处死后浸人75%乙醇数秒,迅速开胸摘取心脏,置人盛有37℃预热的台氏液100ml的培养皿中.在超净工作台上用台式液清洗并修剪掉结缔组织,迅速行主动脉插管.将心脏悬挂于Langendroff灌流装置上,剪下心室并剪成约1mm3,的组织块,放人37℃预热的含0.2mmol/L Ca2+台氏液20ml的培养皿中,将心室在溶液中轻轻晃动以分散已解离的心室肌细胞.新分离的细胞在常温下放置1-2h后,用加样器取带少许细胞的原液放人试管中,加人指示剂,给予正常细胞外液灌流,测全细胞胞内钙瞬变作为前对照组;给予硝苯地平溶液灌流,测全细胞胞内钙瞬变作为实验组;给予正常细胞外液灌流,测全细胞胞内钙瞬变作为后对照组.结果:不同浓度的硝苯地平对静息状态下心室肌细胞胞内钙信号的影响都不明显,仅10umol/L硝苯地平可能使静息状态下心室肌细胞胞内钙水平轻微降低,更高浓度的硝苯地平的效果反而减弱.不同浓度的硝苯地平都能不同程度降低心室肌细胞胞内钙瞬变的峰值(P<0.05),5umol/L硝苯地平的标准化值最低,降低心室肌细胞胞内钙瞬变峰值的效果比2umol/L硝苯地平明显(P<0.05).但是10umol/L硝苯地平、50umol/L的硝苯地平的降低心室肌细胞胞内钙瞬变峰值的效果反而减弱.结论:硝苯地平可以抑制大鼠心室肌细胞的电流.但是,硝苯地平对于静息状态下的心室肌细胞胞内钙信号的影响不明显,可能与硝苯地平只对去极化过程的I(Ca)2+、Ito和Ik有抑制作用有关.     

中西医结合治疗急性胰腺炎

我院于 1997年 10月至 2 0 0 1年 10月采用中药加硝苯地平(硝苯啶 )联合治疗急性胰腺炎 ( AP) ,取得了良好的效果 ,现报告如下。1　临床资料1.1　一般资料　 4 0例中 ,男 10例 ,女 30例。 2 0～ 30岁 7例,31～ 4 0岁 2 3例 ,4 1～ 5 0岁 6例 ,5 1岁以上 4例。 34例有不同程度的发热 ,体温 37.5～ 4 0°C。4 0例都有上腹持续性疼痛 ,阵发性加剧。 36例伴有恶心、呕吐。 5例出现黄疸。全部病例均有上腹部压痛 ,血、尿淀粉酶增高 ,白细胞计数及中性粒细胞增高 ,不同程度的血钙降低 ,血糖升高2　治疗方法2 .1　中医治疗　治法 :利胆清胰 ,清热…     

生长激素对急性胰腺炎大鼠胰腺微循环改变的影响

目的 观察急性胰腺炎(AP)大鼠胰腺微循环功能的变化及重组人生长激素(rhGH)对其影响.方法 采用ip E. coli复制大鼠AP模型,SD大鼠随机分为对照组(C组)、AP组及rhGH治疗组(T组).C组仅ip生理盐水(15 ml·kg<'-1>);AP组ipE.coli(1×10<'10> CFU·L<'-1>,15 ml·kg<'-1>);T 组于ip E. coli后,im rhGH 2.25 U·kg<'-1>·d<'-1>.AP、T组又依观察时点再分为1、3 d两个亚组.采用异硫氰酸荧光素标记红细胞(FITC-RBC)技术及微循环观测系统观察胰腺微循环的变化.结果 AP组大鼠胰腺微循环红细胞流量、血液流速、血管数及功能血管数均明显低于C组的水平,尤以1 d时最为明显;T组大鼠的均明显高于AP组的水平,尤以3 d时最为明显.结论 rhGH可明显改善AP大鼠胰腺微循环功能的障碍.     

间硝地平对左室肥厚大鼠左室舒张功能及心脑线粒体和血管组织钙含量的影响

用肾性高血压左室肥厚(LVH)大鼠模型,观察了间硝地平(m-Nif)和硝苯地平(Nif)长期给药(ig20mg·kg^-1·d^-1持续9周)对左室舒张功能、左心室肌和大脑线粒体及血管钙含量的影响。与假手术组相比,LVH组左室顺应性明显下降,僵硬度增高,左心室肌和大脑线粒体及尾动脉和主动脉钙含量增加。与LVH组相比,m-Nif和Nif各组左室顺应性改善,僵硬度降低(P<0.01),左心室肌线粒体及尾动脉和主动脉钙含量较LVH组显著降低(P<0.01)。两药在作用强度上无显著差异。     

清胰利胆颗粒对胰腺炎大鼠TNF-α的影响

目的:探讨清胰腺利胆颗粒对胰腺炎大鼠TNF-α的影响.方法:采用胆胰管逆行注射法制作大鼠急性胰腺炎(AP)模型,并通过测定肿瘤坏死因子(TNF-α)浓度对清胰腺利胆颗粒进行药效学研究.结果:清胰腺利胆颗粒各剂量组均降低了TNF-α浓度,中、高剂量组的TNF-α浓度与AP模型组相比均有显著性差异(P＜0.05,P<0.0...     

清胰汤在重急性胰腺炎治疗中的作用

目的 观察中药清胰汤治疗重症急性胰腺炎（SAP）的临床疗效。方法 132例SAP患者随机分为治疗组（70例）和对照组（62例），两组均给予常规治疗，治疗组加用清胰汤，每日1剂，分4次从胃管注入。分别观察两组患者平均腹胀消退时间、平均禁食时间、平均住院时间、手术率、胰周感染率并进行比较。结果 治疗组的各项观察指标明显优于对照组（t检验，P〈0．05）。结论 中药清胰汤能明显促进胃肠道功能恢复，减少肠道细菌移位．减轻急性炎症反应综合征，减轻胰腺损害，促进胰腺修复，提高疗效，缩短疗程。     

丹参和氢化可的松对重症急性胰腺炎大鼠三磷酸肌醇及钙代谢的影响

目的:观察重症急性胰腺炎(SAP)动物模型三磷酸肌醇(IP3)的变化及与钙代谢的关系和丹参及糖皮质激素的影响。方法:50只SD大鼠随机分5组:SAP模型组(SAP组)、丹参治疗组(A组)、氢化可的松治疗组(B组)、丹参加氢化可的松治疗组(AB组)和对照组(C组),各10只。SAP组逆行胰胆管注射3%牛磺胆酸钠建立SAP模型,C组则注射生理盐水(NS)。SAP组和C组术后行阴茎背静脉注射NS;A组、B组和AB组如SAP组一样建立模型,术后分别注射丹参、氢化可的松、丹参加氢化可的松。18 h后,观察各组胰腺细胞IP3和细胞内钙(Ca2+)、血清肿瘤坏死因子α(TNF-α)、血清钙(血钙)和淀粉酶(AMY),以及胰腺的病理改变。结果:SAP组IP3、Ca2+、TNF-α、AMY和胰腺病理评分(PSP)显著高于A组、B组、AB组和C组(p0.05),其中AB组明显低于A组和B组(p0.05),但A、B组间无明显差异(p0.05);C组的PSP明显低于A组、B组和AB组(p0.05),C组的IP3和Ca2+明显低于AB组(p0.05),AB组与C组的TNF-α间无明显差异(p0.05);IP3与Ca2+,IP3与TNF-α间呈明显正相关(r分别为0.987和0.937,p0.05);血钙则是SAP组显著低于A组、B组、AB组和C组(p0.05),AB组和C组分别明显高于A组和B组(p0.05),AB组显著低于C组(p0.05),但A组与B组间无明显差别(p0.05)。IP3、Ca2+和TNF-α与血钙为负相关(r分别为-0.997、-0.980和-0.915,p0.05)。结论:SAP大鼠胰腺细胞IP3显著升高;IP3与Ca2+和TNF-α水平呈明显正相关,前三者与血钙呈负相关,IP3可能是引起细胞内外钙和TNF-α变化的重要原因之一;丹参和糖皮质激素均可抑制SAP大鼠胰腺细胞IP3和Ca2+及TNF-α的释放,促进血钙水平回升,胰腺组织病理损害减轻,联合使用丹参和氢化可的松具有协同作用。     

The Effect of Nifedipine on the Isolated Rat Heart

Abstract The mode of action of a calcium-antagonistic drug, nifedipine, on the spontaneously beating, isolated, perfused rat heart was studied at two different calcium concentrations of the Ringer solution, [Ca⁺⁺]_o, (2.0 and 5.0 meq./l). The sinus node discharge, the aortic pressure amplitude and hence the work index were greater at 5.0 than at 2.0 meq./l. Nifedipine 100 μg/1 caused a reduction in these parameters, the effects being most pronounced at the lowest [Ca⁺⁺]_o studied. ECG tracings demonstrated that the PR-interval was longer at 2.0 than at 5.0 meq./l of calcium. The AV conduction time further increased after the addition of nifedipine. This effect was enhanced at the lowest [Ca⁺⁺]_o used, where varying degrees of AV block occurred in several experiments. The drug also reduced the R-wave voltage and the RT-interval. Calcium-induced ventricular tachyarrhythmias were produced, which were suppressed by nifedipine. Nifedipine 100 μg/l produced a small and transient increase in the coronary flow, but a tremendous increase in the ratio coronary flow/work index was observed. This indicates improvement of the cardiac energy balance caused by an increase in the coronary oxygen supply in relation to the myocardial oxygen demand.     

N-三甲基壳聚糖对硝苯地平片在犬体内药物动力学的影响

目的:研究N-三甲基壳聚糖(TMC60)对硝苯地平片药物动力学的影响。方法:以Beagle犬为实验动物,分别口服硝苯地平片Ⅰ(含TMC60)及硝苯地平片Ⅱ(不含TMC60),采用单剂量交叉实验,在预定的时间点取血样,测定硝苯地平的浓度,并用3P97软件包拟合两种片剂的药代动力学参数。结果:硝苯地平片Ⅰ、Ⅱ在犬体内均符合口服吸收二室模型。两种片剂的主要参数T_(max)、C_(max)、Ka、AUC等均有显著性差异(P<0.05)。结论:TMC60可显著改善硝苯地平在犬体内的吸收,提高其生物利用度,是一种较好的促进吸收的辅料。     

The Effect of a Calcium-antagonistic Drug,Nifedipine, on the Rat Atrial Action Potential at Different Calcium Levels

Abstract: Increasing concentrations of calcium in the Ringer solution, [Ca⁺⁺]_O, increased the maximum rate of rise (dv/dt) of the intracellularly recorded action potential of electrically stimulated, isolated rat left atria; while a drug with calcium-antagonistic activity, nifedipine 100 μg/l, reduced dv/dt. The duration of the action potential was shortened with increasing [Ca⁺⁺]_O. A further reduction in the time for 50 and 90 per cent of the repolarization was observed after the administration of nifedipine. All effects of nifedipine on the action potential were most pronounced at the lowest [Ca⁺⁺]_O studied (2.0 meq./l). At the highest [Ca⁺⁺]_O used (8.0meq./l) the effects of this drug were negligible. It is concluded that in the present in vitro experiments, a Ca⁺⁺ current seems to influence the rapid phase of depolarization of the rat left atrium.     

Protective Effect of Nifedipine Against Cytotoxicity and Intracellular Calcium Alterations Induced by Acetaminophen in Rat Hepatocyte Cultures

ABSTRACT

Alteration of calcium homeostasis has been proposed to play a major role in cell necrosis induced by a variety of chemical agents such as acetaminophen (APAP). In this study, a potential protective effect of the dihydropyridine calcium channel blocking agent, nifedipine, was investigated in vitro on acetaminophen-induced hepatocyte damage. Rat hepatocytes were exposed during 20 hours to various concentrations of APAP (0.50 to 4.00 mM). The following metabolic and functional parameters were investigated : - lactate dehydrogenase (LDH) release as an indicator of plasma membrane integrity, - cell viability evaluated by the colorimetric MTT assay, and intracellular calcium concentration as evaluated by two fluorimetric methods : a scanning laser cytometer using indo-1-AM as fluorescent probe and a fluorescence plate reader using fluo-3-AM as calcium indicator.

Incubation of hepatocytes with APAP alone in the range 0.50 to 4.00mM resulted in a dose-response relationship with regard to LDH release (243% to 750% of control) and to the loss of cell viability (0 to 67% of control). Moreover these results were correlated with a significant increase in cytosolic calcium content (189 to 406 nM).

Nifedipine treatment prior to APAP exposure, partially prevented LDH release, the plasma membrane blebbing, and thereby the loss of viability. In addition, intracellular calcium level progressively returned within the limits of the control values with increasing concentrations of nifedipine.

It can be concluded that, in in vitro conditions, nifedipine pretreatment exhibits a preventive effect against acetaminophen hepatocyte injury.     

硝苯地平缓释片体内外相关性模型的建立与评估

目的 建立和评价硝苯地平缓释片体内外相关性(IVIVC)的模型. 方法 筛选不同处方片剂的体外释放条件,采用高效液相色谱(HPLC)法测定其累积释放百分率(Fd);液相色谱串联-质谱(LC-MS/MS)法测定健康志愿者单剂量口服两种不同释放速率的硝苯地平缓释片后的血药浓度,利用Wagner-Nelson方程计算累积吸收百分率(Fa). 结果两种制剂体外释放与体内累积吸收相关性均良好,用与硝苯地平控释片生物等效的制剂,创建IVIVC模型： Fa＝0.831 4 Fd＋0.005 2,r＝0.980 8(P<0.01);用另一种制剂对其模型进行外部预测能力的评估：AUC_0～24和 C_max的预测误差分别为3.2%,3.5%. 结论 IVIVC模型具有良好的预测硝苯地平缓释片体内吸收的能力,为硝苯地平缓释片质量标准制订提供依据.     

高脂血症性急性胰腺炎发生机制的研究进展

目的：高脂血症能够诱发和加重急性胰腺炎的胰腺损伤,其机制包括游离脂肪酸的毒性作用、加速胰蛋白酶原活化、加重胰腺微循环障碍、增加胰腺组织氧自由基生成和核因子-KB活性等,深入探索其确切机制,对于及时诊断和合理治疗高脂血症性急性胰腺炎具有重要意义。     

The Effect of Nifedipine on Isolated Human Peripheral Vessels

Abstract Isometric tension was recorded in ring preparations of human peripherial arteries and veins contracted by potassium (127 mM) and noradrenaline (1.8 × 10^-5 M). In the veins, nifedipine had a marked relaxing effect on contractions induced by both agents, and also reduced the contractile amplitude when added prior to stimulation. The inhibiting effect of nifedipine was more marked on the potassium than on the noradrenaline-evoked responses. This was in contrast to verapamil, which inhibited the noradrenaline-induced contractions significantly more, than those produced by potassium. After immersion of the vein preparations in calcium-free medium for 30 min., the potassium contracture decreased to 26±2.0% (mean ± S.E.M.) of the response in normal Krebs solution, and the noradrenaline-evoked response to 7.1±0.8%. The responses to both agents were completely restored when the calcium concentration was increased from 0 to 4 mM. Nifedipine (1.5 × 10^-7 M) depressed the potassium contracture in calcium-free solution to 7.3±1.6%, and the noradrenaline response to 5.5±1.6%; on addition of calcium, the response elicited by potassium increased to 16±1.7%, and that by noradrenaline to 56±8.6%. Compared with its actions on the veins, the effect of nifedipine on the arterial preparations was less pronounced. In the arteries, too, the inhibiting effect of nifedipine was significantly more pronounced on the potassium than on the noradrenaline-induced contraction. Immersion for 30 min. in calcium-free medium reduced the response to potassium to 61±6.0% and that to noradrenaline to 68±5.6% of the control in normal Krebs. Nifedipine (2.9 × 10^-7 M) further reduced the potassium contraction to 20±4.0%; the response to noradrenaline was unaffected, being 74±6.4% of the control.     

川芎嗪甲酸对平滑肌细胞游离钙浓度的影响

研究川芎嗪代谢产物川芎嗪甲酸（CTPZ）对大鼠阴茎海绵体平滑肌细胞（PCSMC）胞质内游离钙离子浓度的影响。方法：用新型Ca^2＋荧光染色剂Fluo-3／AM负载大鼠PCSMC,细胞分为氯化钾（KCl）和去甲肾上腺素（NE）作用组,应用激光扫描共聚焦显微镜（LSCM）实时测定胞质内[Ca^2＋]的变化,分别观察不同浓度的CTPZ对高钾和NE诱导胞质内钙浓度升高的影响,并与母药川芎嗪作用相比。结果：静息状态下,CTPZ对大鼠PCSMC胞质内[Ca^2＋]无明显影响。1,10,100μmol·L^-1 CTPZ能显著抑制高钾诱发的细胞内的钙浓度升高的影响,抑制率分别为（39．84-4．3）％,（49．2±3．6）％,（58．2±3．9）％。也能抑制1μmol·L^-1 NE诱发钙库释放的细胞内[Ca^2＋]升高,抑制率分别为（20．8±3．9）％,（32．3±2．5）％,（43．7±3．2）％。结论：CTPZ对大鼠PCSMC电压依赖性钙通道和细胞内钙库释放的抑制作用,能降低PCSMC胞质内[Ca^2＋]水平,其作用效果比母药川芎嗪佳。     

奥曲肽保护急性胰腺炎患者肠黏膜屏障功能的疗效观察

目的：观察奥曲肽保护急性胰腺炎患者肠黏膜屏障功能的疗效和安全性。方法： 64例急性胰腺炎患者随机分为奥曲肽组和对照组各32例。两组均予以禁食禁饮、胃肠减压、解痉镇痛、预防感染和静脉营养支持等对症治疗,奥曲肽组在此基础上加用奥曲肽100 μg,ih,q8h,连用1周。观察两组患者治疗前后血清内毒素、D 乳酸和肿瘤坏死因子 α（TNF α）水平的变化,比较两组临床疗效和药品不良反应。结果：治疗1周后,两组患者血清内毒素、D 乳酸和TNF α水平均较治疗前明显下降（P〈0.05或0.01）,且奥曲肽组下降值明显大于对照组（P〈0.05）;奥曲肽组临床总有效率明显高于对照组（P〈0.05）。对照组和奥曲肽组治疗期间发生不良反应2例和5例,症状均较轻,两组比较,差异无统计学意义（P〉0.05）。结论：奥曲肽治疗急性胰腺炎有效,尤其是轻型患者,能降低血清内毒素、D 乳酸和TNF α水平,保护肠黏膜屏障功能,安全性好。     

生长抑素和奥曲肽在治疗急性胰腺炎中的应用观察

目的对比分析生长抑素和奥曲肽在治疗AP中的作用。方法本文的研究对象为2009年3月至2012年3月间在我院确诊为AP的患者73例,观察治疗前后的血尿淀粉酶和治疗效果。结果奥曲肽在降低血尿淀粉酶方面的作用较生长抑素强,且治疗的有效率达到了86.84%高于奥曲肽的80.00%,且有统计学意义(P<0.05)。结论奥曲肽的疗效好于生长抑素,但是疗效差别并不大,均可用于AP的治疗。