超声造影定量分析L-精氨酸改善大鼠肾缺血再灌注损伤的应用价值

目的应用超声造影技术定量分析L-精氨酸对大鼠肾缺血再灌注损伤肾皮质血流灌注的影响,探讨超声造影技术在评价药物干预肾缺血再灌注损伤疗效中的应用价值。方法健康雄性大鼠24只随机分成假手术组(Sham组)、缺血再灌损伤组(I/R组)和L-精氨酸组(L-arg组),每组8只。行超声造影检查观察肾皮质血流灌注情况并脱机分析时间-强度曲线(TIC)。实验结束后,行肾组织病理学检查。结果与假手术组比较,I/R组和L-arg组肾脏病理改变明显,达峰时间(TTP)和平均通过时间(MTT)延长,曲线下面积(AUC)显著增加(P0.05);与I/R组比较,L-arg组病理改变显著,峰值浓度(Peak)增高,TTP、MTT缩短,AUC减少(P0.05)。结论超声造影结合时间-强度曲线能定量分析L-精氨酸对大鼠肾缺血再灌注损伤肾皮质血流灌注的改善。     

超声造影监测缺血再灌注损伤兔肾皮质血流动力学改变的实验研究

目的:采用超声造影(CEUS)定量分析技术动态监测肾缺血再灌注损伤(Renal ischemia reperfusion injury,RIRI)后兔肾皮质血流灌注的改变.方法:54只家兔随机分为正常对照组,肾缺血后再灌注第2h组、第16h组、第24 h组、第3d组、第5d组.行CEUS并应用时间-强度曲线测量灌注峰值时间(TTP)、曲线上升支斜率(β)、灌注峰值强度(A)、曲线下面积(AUC),观察各参数的变化并分析与病理改变的相关性.结果:肾缺血恢复灌注后各组与对照组相比TTP值增加,β值降低,AUC增大(P＜0.05);缺血再灌注组各组间TTP、β有统计学差异,其中恢复灌注后第3d的TIP的延长和β的下降最为显著(P＜0.01).A值在RIRI后第16h,24 h,3d较对照组降低(P＜0.05),第3d最为显著(P＜0.01).结论:CEUS定量分析技术能在缺血再灌注损伤发生后早期发现肾皮质血流灌注的异常,肾缺血再灌注损伤早期即发生肾皮质微循环障碍,在第3d肾皮质微循环灌注受损最为严重,度过这一“危险期”,肾皮质微循环受损得以改善,CEUS定量分析技术能敏感反映这一过程.     

超声造影监测兔肾缺血再灌注损伤早期皮质血流动力学的改变

目的采用超声造影定量分析技术监测肾缺血再灌注损伤发生后早期兔肾皮质血流灌注的改变。方法 36只家兔随机分为假手术组(R0组)、缺血后再灌注第2小时组(R1组)、第16小时组(R2组)、第24小时组(R3组),每组各9只。行超声造影并应用时间-强度曲线(TIC)测量灌注峰值时间(TTP)、曲线上升支斜率(β)、灌注峰值强度(A)、曲线下面积(AUC),观察各参数的变化并对比与兔肾病理改变的相关性。结果肾缺血恢复灌注后各组与对照组相比TTP、AUC增大,β值、A值降低(P<0.05);缺血再灌注组各组间TTP、β有统计学差异(P<0.05),其中恢复灌注后第24 h的TTP的延长和β的下降最为显著(P<0.01)。结论 肾缺血再灌注损伤早期即发生肾皮质微循环障碍,超声造影定量分析技术能敏感反映这一过程。TIC曲线各定量参数对于评价肾局部微循环灌注具有参考价值,其中TTP及β更具意义。     

超声造影对兔肾缺血再灌注损伤的实验研究

目的 评价灰阶超声造影及其量化分析技术在兔肾缺血再灌注损伤皮质显像中的诊断价值.方法 建立兔肾缺血再灌注模型,15只家兔被分为术前对照I_0组,术后不同缺血时间组(I_1-I_3),用超声造影观察各组肾灌注模式并分析灌注峰值时间 (TP)、灌注峰值强度(A)、曲线上升斜率(β)、曲线下面积(AUC).结果 随着缺血时间增加,超声造影显示肾皮质灌注回声逐渐变弱.灌注参数值中TP呈增加趋势,β逐渐降低,AUC先升后降,A无明显变化;与对照组比较,TP、 AUC、β、A均具有显著差异.结论 超声造影及其量化分析技术可以无创地判断肾缺血再灌注损伤程度.     

IL-1β在缺血预处理对大鼠肾脏冷缺血再灌注损伤中第二窗保护作用的实验研究

目的：探讨IL-1β在缺血预处理对大鼠肾脏冷缺血再灌注损伤模型中第二窗保护的作用。方法：36只SD大鼠制备成肾脏冷缺血再灌注损伤模型，随机分为假手术组（A组）、冷缺血再灌注组（B组）、缺血预处理组（C组）。免疫组化观察IL-1β表达，测定肾功能变化，TUNEL法检测肾组织细胞凋亡情况。结果：B组、C组血浆尿素氮、肌酐测定值均〉A组（P〈0．01），而C组〈B组（P〈0．01）；B组、C组IL-1β表达及原位细胞凋亡指数均〉A组（P％0．01），而C组〈B组（P〈0．01）；肾组织损伤的病理分级显著减轻（P〈0．01）。结论：缺血预处理对肾脏冷缺血再灌注损伤第二窗具有保护作用，其机制可能与IL-1β表达减少有关。     

大鼠肾脏冷缺血-再灌注损伤模型的建立

目的　建立一种简便、实用的大鼠肾脏冷缺血再灌注损伤模型,为研究缺血再灌注损伤与移植后肾脏损伤的关系提供实验基础。方法　雄性SD大鼠36只,腹正中切口,采用显微外科技术在后腹膜间隙游离左、右侧肾蒂、肾脏和腹主动脉和下腔静脉。实验组(A组)和对照组(B组)各18只。A组:阻断左侧肾脏血流,2 4GA静脉留置针经腹主动脉缓慢匀速灌注10mL0℃～4℃HC A液至肾脏颜色变白,缺血1h后恢复左肾血流,切除右肾;B组:假手术组,采用同样方法游离左右侧肾脏后,不实施阻断左肾脏血流和肾脏灌注,切除右肾;A、B组分别于肾脏复灌后1d、3d、7d检测肾功能和切除左肾作病理检查。结果　A组1d和3d血清Cr、Bun值均高于B组,差异无统计学意义(P <0 .0 1) ;7d时血清Cr、Bun值略高于B组,但差异无统计学意义(P >0 .0 5 ) ;A组术后1d和3d肾脏病理切片可见典型肾脏缺血再灌注损伤改变,B组未见明显改变。结论　大鼠肾脏冷缺血再灌注损伤模型手术操作简便,手术成功率高,充分模拟临床上肾移植时以冷缺血为主的特点,是研究肾脏移植缺血再灌注损伤的理想动物模型。     

缺血预处理对大鼠冷缺血再灌注损伤的保护作用的实验研究

目的：探讨缺血预处理对大鼠肾脏冷缺血再灌注损伤的保护作用。方法：36只SD大鼠制备成肾脏冷缺血再灌注损伤模型，随机分为假手术组（A组）、冷缺血再灌注组（B组）、缺血预处理组（C组），免疫组化观察Bcl2、Bax蛋白表达，测定肾功能、肾组织超氧化物歧化酶、丙二醛，病理切片观察肾组织损伤形态学的变化。结果：B组、C组BUN、CR测定值均显著高于A组，而C组低于B组，差异具有显著性（P〈0.01）；C组大鼠肾组织超氧化物酯化酸水平较B组显著升高，而丙二醛水平显著性下降（P〈0．01）；B组、C组Bcl2、Bax蛋白较A组均明显增加，C组较B组Bcl—2表达显著增强，Bax表达明显下降（P均〈0．01），肾组织损伤的病理分级显著减轻。结论：缺血预处理对肾脏冷缺血再灌注性损伤具有保护作用，其机制可能与上调Bcl2和下调Bax蛋白表达相关。     

高迁移率族蛋白B1在肾脏冷缺血再灌注损伤中的作用

背景:缺血再灌注损伤是临床器官移植不可避免的病理生理过程,冷缺血再灌注损伤具有研究肾移植更强的针对性.目的:观察高迁移率族蛋白B1在大鼠肾脏冷缺血再灌注损伤中的作用.方法:将SD大鼠随机分为假手术组、冷缺血再灌注组、丙酮酸乙酯(可显著抑制高迁移率族蛋白B1的合成与释放)治疗组.冷缺血再灌注组和丙酮酸乙酯治疗组制冷缺血再灌注模型前分别经阴茎背静脉注射林格液与丙酮酸乙酯,假手术组将腹腔打开后经阴茎背静脉注射林格液,45 min后关闭腹腔.结果与结论:冷缺血再灌注组和丙酮酸乙酯治疗组各时间点肌酐、高迁移率族蛋白B1、肿瘤坏死因子α、核因子κB水平均显著高于假手术组(P < 0.01),其中冷缺血再灌注组上述指标高于丙酮酸乙酯治疗组(P < 0.01).表明高迁移率族蛋白参与了肾移植冷缺血再灌注的病理过程,丙酮酸乙酯能够减轻肾脏冷缺血再灌注损伤.     

缺血后处理减轻脑皮质缺血-再灌注损伤

目的 观察缺血后处理对脑皮质缺血-再灌注期间神经元凋亡及磷酸化糖原合酶激酶-3β(GSK-3β)的影响,探讨其保护作用机制.方法 实验在武汉大学人民医院动物实验中心进行,雄性Wistar大鼠30只,随机(随机数字法)分为3组(n=10):假手术组(S)、缺血-再灌注组(I/R)及后处理组(IPost).采用4-VO法建立大鼠全脑缺血-再灌注模型.IPost组分离双侧颈总动脉夹闭10 min,开放30 s,夹闭10 s,反复3次.于术后2d处死大鼠,取出脑组织,采用TUNEL法检测大鼠皮质神经元凋亡情况;TTC法检测大鼠脑部梗死面积;光谱法检测磷酸化GSK-3β水平;统计学软件SPSS 13.0进行单因素方差分析(Student-Newman-Keul test方法检验),采用线性回归分析GSK-3β活性与大鼠皮质神经元凋亡,脑部梗死面积的相关性.结果 与S组相比,I/R组和IPost组皮质神经元凋亡和梗死面积显著增多(P＜0.01),p-GSK-3β水平降低(P＜0.01);与I/R组相比,IPost组皮质神经元凋亡和梗死面积显著减少(P＜0.01),p-GSK-3β水平增高(P＜0.01);p-GSK-3β与大鼠皮质神经元凋亡、脑部梗死面积之间具有高度相关性(P＜0.01).结论 缺血后处理使p-GSK-3β水平增高,脑皮质神经元凋亡和梗死面积减少,从而减轻脑缺血-再灌注损伤.     

超声造影评价兔肾皮质血流灌注

目的 探讨超声造影评价兔肾皮质血流灌注状态的价值.方法 通过结扎肾动脉建立不同程度家兔肾皮质血流减少的模型.经耳缘静脉团注SonoVue(0.05 ml/kg体质量)进行肾灌注超声造影,观察并采集注射造影剂后0～3 min的动态图像,通过时间-强度曲线(TIC)软件分别计算肾动脉结扎前后肾皮质TIC的加速时间(AT)、峰值背向散射强度(A)、峰值减半时间(T)、峰值基础视频强度差(PBD)、TIC斜率(β)以及A·β值,并对以上指标进行t检验及相关分析. 结果 实时观察发现肾动脉结扎前,肾皮质表现为快速明显强化,增强顺序为各级肾动脉-皮质-锥体.结扎后AT明显延长(P<0.001),A显著减小(P<0.001), T明显缩短(P<0.001), PBD明显减低(P<0.001),β明显下降(P<0.002), A·β值显著降低(P<0.001).肾动脉狭窄程度与AT、PBD及A·β呈明显的相关;肾动脉狭窄率在31%～69%之间组与70%～93%之间组比较,后者较前者AT延长(P<0.001),A减小(P<0.029), PBD减低(P<0.001), A·β值降低(P<0.02). 结论超声造影剂和造影专用成像技术可灵敏地反映肾皮质微小血管的血流变化,在评价肾皮质的血流灌注状态方面有很高的应用价值.     

Effects of angiotensin II and noradrenaline on intrarenal haemodynamics in the rat.

The haemodynamic effects of angiotensin II and noradrenaline were studied in the rat kidney. These pressors were given by intravenous infusion in stepwise increasing doses. Intrarenal haemodynamics were analyzed by the 133xenon washout technique, 85krypton autoradiography and silastic casting of the renal vascular tree. Angiotensin II induced significant changes in intrarenal haemodynamics before any changes in systemic blood pressure were detected. The decrease in mean renal blood flow (2.91 ml.min-1.g-1 in controls, 1.76 ml.min-1.g-1 in rats given 50 mug of angiotensin II.kg-1.h-1) reflects a reduction in component I blood flow rate (from 3.9 to 2.9 ml.min-1.g-1) as well as a decrease in the fraction of total renal blood flow supplied to component I of the washout curve (from 84% to 62%). With noradrenaline an increase in total renal resistance occurred simultaneously with the elevation of mean arterial blood pressure. The resulting reduction in mean renal blood flow (from 2.76 ml.min-1.g-1 in controls to 1.55 ml.min-1.g-1 in rats given 1000 mug of noradrenaline kg-1.h-1) reflects a decrease in component I blood flow rate with lower infusion rates and a drop in component I flow fraction (from 82% to 52%) whith higher doses. In contrast to canine kidneys, no evidence for a patchy cortical vasoconstriction was found in the rat. Using autoradiography it was possible to attribute component I to the renal cortex and subcortical area of the kidney.     

Haemodynamic consequences of experimental papillary necrosis in the rat

Experimental renal papillary necrosis induced by 2-bromoethylamine hydrobromide (BEA) results in hypertension in the rat. The haemodynamics of this increase in blood pressure were investigated with radiolabelled microspheres, thus enabling individual organ blood flows to be evaluated. Total peripheral resistance was raised in BEA-treated rats (3.6 +/- 0.3 mmHg ml-1 min X 100 g) compared with control rats (2.87 +/- SEM 0.2, P less than 0.05) whilst cardiac index remained similar (39.9 +/- 3.6 vs 39.2 +/- 3.1 ml min-1 100 g-1). Heart and brain from BEA rats demonstrated a significant rise in vascular resistance with a normal blood flow. In the kidneys vascular resistance increased still further and here there was a reduction in renal blood flow despite an increase in kidney size. These findings are compatible with a loss of renomedullary vasodepressor mechanisms acting directly or indirectly on the resistance vessels.     

Influence of nifedipine on cyclosporin A nephrotoxicity after unilateral nephrectomy in the spontaneously hypertensive rat.

1. Nifedipine ameliorates cyclosporin A-induced renal impairment in surgically intact (two-kidney) rats. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in spontaneously hypertensive rats after either uninephrectomy or uninephrectomy with contralateral renal denervation. 2. Fourteen days after uninephrectomy pair-fed rats were injected for 14 days with cyclosporin A (25 mg/kg body weight) via the subcutaneous route and with nifedipine (0.1 mg/kg body weight) via the intraperitoneal route. Renal and systemic haemodynamics were measured in conscious unrestrained rats. 3. Whole-blood levels of cyclosporin A did not differ between groups (overall 352 +/- 22 ng/ml, means +/- SEM). After uninephrectomy, cyclosporin A decreased the glomerular filtration rate (olive oil versus cyclosporin A: 0.96 +/- 0.04 versus 0.70 +/- 0.06 ml min-1 100 g body weight, P less than 0.02) and effective renal plasma flow (1.94 +/- 0.10 versus 1.38 +/- 0.13, P less than 0.01), and increased renal vascular resistance [(20.2 +/- 1.8) x 10(4) versus (31.6 +/- 3.3) x 10(4) kPa l-1 s [(20.2 +/- 1.8) x 10(3) versus (31.6 +/- 3.3) x 10(3) dyn s cm-5], P less than 0.02] and mean arterial pressure (146.7 +/- 6.7 versus 167.3 +/- 2.9 mmHg, P less than 0.05). Neither renal denervation nor nifedipine prevented the reduction in glomerular filtration rate or effective renal plasma flow induced by cyclosporin A. 4. This study infers that the sympathetic nervous system does not play an active role in cyclosporin A nephrotoxicity and demonstrates that the concomitant administration of nifedipine to rats with reduced renal mass does not ameliorate cyclosporin A-induced renal impairment.     

A renorenal suppression in response to atrial natriuretic peptide in the unilateral ischaemic rat

1. The present study was carried out to investigate the haemodynamic and natriuretic effects of atrial natriuretic peptide (ANP) in normal rats and in rats with unilateral ischaemia. 2. Twenty-four hour unilateral ureter occlusion gave rise to a marked vasoconstriction in the ipsilateral kidney after its release. Intravenous infusion of ANP doubled p-aminohippurate clearance and inulin clearance and elicited massive natriuresis in the hydronephrotic kidney, while in the contralateral kidney these clearance values were decreased and there was a lack of natriuresis. The responses in the latter kidney were also different from those in the normal rat, in which significant natriuresis was elicited by ANP even though a decrease in p-aminohippurate clearance occurred. 3. After the control kidney in the unilateral hydronephrotic rat was denervated either mechanically or by pretreatment with prazosin, ANP induced a natriuresis in both kidneys. Furthermore, the renal denervation prevented the decrease in inulin clearance in the control kidney after ANP administration. 4. These findings suggest that the renal response to ANP may depend on the vascular tone before administration, and that renal nerve activity may modify the effects of ANP on renal haemodynamics and sodium excretion.     

Increase of glomerular filtration rate and renal plasma flow by insulin-like growth factor-1 during euglycaemic clamping in anaesthetized rats

Renal function was studied in anaesthetized rats receiving i.v. infusions of recombinant human insulin-like growth factor-I (IGF-I) under euglycaemic clamp conditions. IGF-I increased glomerular filtration rate up to 35% and renal plasma flow up to 100%, this increase being dose dependent with half-maximal stimulation at serum IGF-I concentrations of about 24 pmol ml-1. Renal vascular resistance was reduced up to 50%, filtration fraction decreased up to 30% and urine flow increased up to three fold while arterial blood pressure was unchanged. Renal haemodynamics were affected at serum IGF-I concentrations that did not stimulate total body glucose disposal during euglycaemic clamping. IGF-I seemed to regulate renal function through IGF-I receptors apparently independent of acute changes of glucose metabolism.     

Blood pressure and renal haemodynamic response to salt during the normal menstrual cycle

The purpose of the present study was to evaluate prospectively blood pressure and the renal haemodynamic response to salt during the normal menstrual cycle. A total of 35 healthy normotensive young women not on oral contraceptives were enrolled; 17 were studied in the follicular phase and 18 in the luteal phase of the menstrual cycle. The women in each group were then randomly allocated to receive a low-sodium (40 mmol/day) or a high-sodium (250 mmol/day) diet for a 7-day period in two consecutive menstrual cycles. At the end of each dietary period, 24 h ambulatory blood pressure, urinary sodium excretion, plasma renin activity, plasma catecholamine levels and renal haemodynamics were measured. Our results show that the blood pressure response to salt is comparable during the luteal and the follicular phases of the normal menstrual cycle and is characterized by a salt-resistant pattern. In the kidney, effective renal plasma flow was significantly greater and the filtration fraction lower (P<0.05) after salt loading in women studied in the luteal phase compared with women investigated in the follicular phase. This study thus demonstrates that the female hormone status does not affect the blood pressure response to sodium in young normotensive women. However, in contrast with systemic haemodynamics, the renal response to salt varies during the normal menstrual cycle, suggesting that female sex hormones play a role (direct or indirect) in the regulation of renal haemodynamics.     

Effects of dopexamine on rat cardiorenal functions during lipopolysaccharide-induced experimental sepsis

We aimed to test the protective effect of dopexamine on renal function and systemic haemodynamics in rats with induced sepsis. Female Sprague-Dawley rats were randomized into three equal groups: group 1 (control, received 3% creatinine throughout the experiment); group 2 (sepsis, received 3% creatinine and Escherichia coli lipopolysaccharide [LPS] endotoxin [8 mg/kg per h]); and group 3 (sepsis plus dopexamine, received 3% creatinine, E. coli LPS and dopexamine [1 microgram/kg per min]). Time-adjusted heart rate, systolic, diastolic and mean arterial pressures, urine volume and glomerular filtration rate (from creatinine clearance) were recorded. After bacterial infusion heart rate increased and mean arterial pressure decreased; the fall in mean arterial pressure was less pronounced with dopexamine (group 3) than without (group 2). Dopexamine also induced significant and moderate increases in urine volume and heart rate, respectively. We concluded that dopexamine has some positive inotropic-chronotropic effects and induces favourable responses in renal function.     

Oestrogen-induced changes in renal haemodynamics in the rat: influence of plasma and intrarenal renin

The effect of oestrone acetate (in total doses of 5 and 10 mg) on systemic and renal haemodynamics and the renin-angiotensin system has been studied in adult female rats. The administration of 10 mg of oestrogen resulted in a significant fall in renal blood flow associated with significant rises in both renal vascular resistance and mean arterial pressure. No changes were noted in cardiac output or total peripheral resistance at either dose. Whilst the higher dose of oestrogen induced a significant increase in plasma renin activity, no change was noted in animals receiving 5 mg of oestrogen. Both regimens caused significant reductions in plasma and intrarenal renin concentrations. Although renal blood flow correlated with plasma renin activity in animals with a normal renal blood flow, no such correlation was noted in animals with oestrogen-induced reductions in renal blood flow. The present study demonstrates that oestrogen-induced reductions in renal blood flow result from a rise in intrarenal vascular resistance which cannot be accounted for by simultaneous changes in either plasma renin activity or renal renin concentration.     

Effect of a kinin antagonist on renal function and haemodynamics during alterations in sodium balance in conscious normotensive rats

1. To evaluate whether sodium intake can modulate the action of endogenous kinins on renal function and haemodynamics, a receptor antagonist of bradykinin was infused in conscious normotensive rats maintained on either a normal or a low sodium diet. 2. The antagonist inhibited the hypotensive effect of exogenously administered bradykinin. It did not change the vasodepressor effect of acetylcholine, dopamine or prostaglandin E2. 3. The antagonist did not affect mean blood pressure, glomerular filtration rate, renal blood flow or urinary sodium excretion, in rats on sodium restriction. It did not change mean blood pressure, glomerular filtration rate or urinary sodium excretion, but decreased renal blood flow, in rats on a normal sodium intake. 4. The kallikrein-kinin system has a role in the regulation of renal blood flow in rats on a normal sodium diet.     

Effect of nifedipine on renal haemodynamics in an animal model of cyclosporin A nephrotoxicity

1. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in the spontaneously hypertensive rat. 2. Cyclosporin A, administered daily by subcutaneous injection at 25 mg/kg body weight for 14 days, induced a significant reduction in glomerular filtration rate (35.3%) and effective renal plasma flow (45.0%), and an increase in renal vascular resistance (219%). Using this regimen, tubular, glomerular or vascular morphological damage was not evident on light microscopy. 3. The administration of nifedipine simultaneously with cyclosporin A from day 1 prevented the characteristic decline in renal function and increase in renal vascular resistance. However, the administration of nifedipine to spontaneously hypertensive rats previously exposed to cyclosporin A for 7 days failed to improve renal haemodynamics. 4. This study suggests that the beneficial effect conferred by nifedipine on cyclosporin A nephrotoxicity is present only when treatment is initiated simultaneously with cyclosporin A.