Effects of caffeic acid phenethyl ester on glycerol-induced acute renal failure in rats

1. Free radicals and nitric oxide (NO) play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). The aim of the present study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an anti-oxidant, on the myoglobinuric ARF induced by intramuscular hypertonic glycerol injection. 2. Thirty rats were divided equally into three groups. Rats in group 1 were given saline and those in groups 2 and 3 were injected with glycerol (10 mL/kg, i.m.). Concomitant and 24 h after glycerol injection, CAPE (10 micromol/kg, i.p.) was administered to group 3 rats. Forty-eight hours after glycerol injection, blood samples and kidney tissues of rats were taken under anaesthesia. 3. Plasma concentrations of urea, creatinine, malondialdehyde (MDA) and NO were determined, as were superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities and MDA levels in kidney tissues. Kidney morphology was also investigated. 4. In the group receiving CAPE, although SOD enzyme activity was found to be increased, we failed to find any protective effect of CAPE on other parameters investigated. Moreover, although CAPE significantly decreased NO levels, it increased plasma concentrations of urea and MDA. 5. We suggest that the effect of CAPE in decreasing NO concentrations may further increase the renal ischaemia in this model. Thus, CAPE may have a worsening rather than beneficial effect under these conditions in this model of ARF.     

汉防已甲素对大鼠急性缺血性肾衰的保护作用

目的 研究汉防已甲素对急性缺血性肾衰的保护作用。方法 术前 ３ｄ开始每天 １次及术前 １ｈ ｉｇ汉防已甲素 ２０ｍｇ／ｋｇ、４０ ｍｇ／ｋｇ。然后制作大鼠肾脏缺血再灌注致急性缺血性肾衰模型，测定肾组织中 ＭＤＡ、ＳＯＤ、Ｎａ＋，Ｋ＋－ＡＴＰ酶和Ｃａ２＋－ＡＴＰ酶含量及切片观察肾脏形态。结果 缺血6０ｍｉｎ再灌注２０ｍｉｎ后肾组织中 ＭＤＡ明显升高，ＳＯＤ、Ｎａ＋、Ｋ＋－ＡＴＰ酶和 Ｃａ２＋－ＡＴＰ酶均显著降低。用药组 ＭＤＡ显著下降，ＳＯＤ和 ＡＴＰ酶均明显升高。病理结果提示再灌注组肾小管上皮明显变性，而用药组损害明显减轻。结论 汉防已甲素对急性缺血性肾衰有一定的保护作用。     

人参总皂甙对缺血性急性肾功能衰竭大鼠肾脏的保护作用

目的 探讨人参总皂甙对缺血性急性肾功能衰竭肾脏的保护作用.方法 采用钳夹右肾蒂1 h再灌注并切除左肾法制备缺血性急性肾功能衰竭大鼠模型,观察再灌注24h后血清BUN、Scr含量,ET-1、NO水平和肾组织病理改变.结果 治疗组大鼠血清BUN、Scr含量与I/R组比较明显下降并有显著差异(P＜0.05),与对照组无差异(P＞0.05);治疗组血清NO水平与I/R组比较明显提高亦有显著差异(P＜0.05);肾组织病理示:治疗组肾小管病变明显轻于I/R组(P＜0.01).结论 人参总皂甙对缺血性肾功能衰竭肾脏有明显保护作用,其对NO水平的调节可能是这一保护作用的机理之一.     

双参苓颗粒剂对慢性肾功能衰竭大鼠肾脏的保护作用

目的观察双参苓颗粒剂对单侧肾切除大鼠慢性肾功能衰竭(CRF)的保护作用。方法通过单侧肾切除加尾静脉重复注射柔红霉素,复制大鼠慢性肾衰模型,动物随机分成6组:正常组、模型组、尿毒清颗粒剂组、双参苓颗粒剂高、中、低剂量(2.70,1.35,0.68 g.kg-1.d-1)实验组,连续给药6周后,检测各组血液学指标、血清生化指标,HE染色观察大鼠肾脏组织病理学变化。结果双参苓颗粒剂高、中剂量(2.70,1.35 g.kg-1.d-1)组的尿蛋白、血清肌酐、尿素氮、甘油三脂和胆固醇水平,显著低于模型组;血浆白蛋白、红细胞、血红蛋白和红细胞压积,明显高于模型组;肾组织病理损伤明显轻于模型组。结论双参苓颗粒剂对CRF大鼠残肾功能有保护作用,呈剂量依赖趋势。     

Protective effect of alpha-lipoic acid against ischaemic acute renal failure in rats

1. In the present study, we investigated whether treatment with alpha-lipoic acid (LA), a powerful and universal anti-oxidant, has renal protective effects in rats with ischaemic acute renal failure (ARF). 2. Ischaemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Blood urea nitrogen (BUN), plasma concentrations of creatinine (Pcr) and urinary osmolality (Uosm) were measured for the assessment of renal dysfunction. Creatinine clearance (Ccr) and fractional excretion of Na+ (FENa) were used as indicators of glomerular and tubular function, respectively. 3. Renal function in ARF rats decreased markedly 24 h after reperfusion. Intraperitoneal injection of LA at a dose of 10 mg/kg before the occlusion tended to attenuate the deterioration of renal function. A higher dose of LA (100 mg/kg) significantly (P < 0.01) attenuated the ischaemia/reperfusion-induced increases in BUN (19.1 +/- 0.7 vs 7.2 +/- 0.7 mmol/L before and after treatment, respectively), Pcr (290 +/- 36 vs 78.1 +/- 4.2 micromol/L before and after treatment, respectively) and FENa (1.39 +/- 0.3 vs 0.33 +/- 0.09% before and after treatment, respectively). Treatment with 100 mg/kg LA significantly (P < 0.01) increased Ccr (0.70 +/- 0.13 vs 2.98 +/- 0.27 mL/min per kg before and after treatment, respectively) and Uosm (474 +/- 39 vs 1096 +/- 80 mOsmol/kg before and after treatment, respectively). 4. Histopathological examination of the kidney of ARF rats revealed severe lesions. Tubular necrosis (P < 0.01), proteinaceous casts in tubuli (P < 0.01) and medullary congestion (P < 0.05) were significantly suppressed by the higher dose of LA. 5. A marked increase in endothelin (ET)-1 content in the kidney after ischaemia/reperfusion was evident in ARF rats (0.43 +/- 0.02 ng/g tissue) compared with findings in sham- operated rats (0.20 +/- 0.01 ng/g tissue). Significant attenuation (P < 0.01) of this increase occurred in ARF rats treated with the higher dose of LA (0.24 +/- 0.03 ng/g tissue). 6. These results suggest that administration of LA to rats prior to development of ischaemic ARF prevents renal dysfunction and tissue injury, possibly through the suppression of overproduction of ET-1 in the postischaemic kidney.     

谷氨酰胺对急性肝功能不全大鼠的防治作用

目的 探讨谷氨酰胺对大鼠实验性急性肝功能不全的防治作用。方法 腹腔注射D-氨基半乳糖（GaiN）建立急性肝功能不全大鼠模型,并测定血清生化指标和肝组织病理检查。结果 肝功能检测显示：遗模后24,48h肝脏损伤程度,与模型组相比,防治组的肝损较轻（P〈0．05）。肝脏病理切片结果：防治组的损伤程度明显轻于模型组,两者差异显著（P〈0．05）。结论 谷氨酰胺对GalN致急性肝功能不全大鼠有明显的保护作用。     

松花粉对甘油诱导大鼠急性肾衰竭的保护作用

目的：研究松花粉对甘油诱发大鼠急性肾衰竭（acute renal failure,ARF）的保护作用及机制。方法：采用双侧后肢注射50%甘油溶液（10 mL·kg-1）诱发大鼠成急性肾衰竭模型,检测大鼠血清肌酐（Scr）、血清尿素氮（BUN）的含量,肾组织中超氧化物歧化酶（SOD）的活性,谷胱甘肽（GSH）、丙二醛（MDA）的含量,同时测定肾组织中一氧化氮（NO）的含量和诱导型一氧化氮合酶（iNOS）的活性;HE染色观察肾病理组织形态学变化。结果：与空白组大鼠相比,模型组大鼠血清Scr和BUN的含量明显上升,肾组织中SOD的活性和GSH的含量显著降低,MDA的含量显著升高;组织病理检查发现,模型组大鼠肾小管损伤明显,肾皮质细胞部分脱落,肾小球肿胀,间质炎性侵润明显。给予松花粉治疗后,可显著降低ARF大鼠血清Scr和BUN,升高肾组织中SOD的活性、GSH的含量,降低MDA的含量,同时发现,松花粉可明显降低肾组织中NO的含量和iNOS的活性,并显著降低肾组织损伤。结论：松花粉对甘油致大鼠ARF具有治疗作用,其作用机制可能与抑制iNOS的活性,降低体内NO过多产生,降低NO相关的脂质过氧化过程有关。     

虫草多糖对庆大霉素诱发的急性肾衰的预防作用

目的：探讨虫草多糖对庆大霉素诱发的急性肾衰的防治作用。方法：将实验动物分为阳性地塞米松磷酸钠组,虫草多糖高、中、低剂量组以及正常对照组、模型组;采用腹腔注射庆大霉素的方法复制大鼠急性肾衰（ARF）模型,造模过程中预防给药。观察大鼠的血液生化指标、肾功能、肾病理、肾指数等指标的变化。结果：预防给药后,阳性对照组和虫草多糖3个剂量组大鼠的血清尿素氮、肌酐的含量,以及尿蛋白和尿量降低,与模型组比较有显著差异（P〈0．01或P〈0．05）,高剂量和中剂量虫草多糖的作用优于阳性对照组。病理切片可见阳性对照组和虫草多糖高剂量组大鼠肾脏病理损伤明显好转,优于中、低剂量组。结论：虫草多糖能够预防大鼠庆大霉素诱发的急性肾衰,改善肾功能。     

碘普罗胺致急性肾衰竭

1例65岁男性2型糖尿病患者,因反应迟钝伴口齿不清入院。头颅磁共振成像示脑梗死(急性期),给予肠溶阿司匹林(0.1g,1次/d)、依达拉奉(30mg,1次/d)及甲钴胺等药物治疗。因胸部、腹部CT增强扫描,连续2d各使用造影剂碘普罗胺100ml(含碘30g),第3天出现双下肢水肿,尿量400ml/24h,随后无尿,静脉给予呋塞米未见好转。复查血肌酐475μmol/L,尿素氮24.5mmol/L。诊断为急性肾衰竭,考虑与碘普罗胺有关。连续血液透析治疗5d后,患者尿量增加,血肌酐降至284μmol/L。17d后血肌酐231μmol/L,尿素氮14.4mmol/L。患者双下肢水肿明显好转,出院。     

万古霉素引起急性肾衰竭

1例36岁男性白血病患者,因肺部感染给予万古霉素1g加入0.9%氯化钠注射液100mL,1次/12h静脉滴注;莫西沙星0.4g,1次/12h静脉滴注。给药3d后实验室检查示SCr549μmol/L,BUN11.17mmol/L,血K＋3.76mmol/L。停用万古霉素,改用利奈唑胺,继续使用莫西沙星。患者情况恶化,出现恶心、下肢水肿、腹胀,尿量1000mL/d,SCr848μmol/L,BUN19.8mmol/L。遂行血液滤过,3次后患者症状消失,肾功能各项指标均恢复正常。     

卡维地洛对顺铂致大鼠急性肾衰竭的预防作用

目的观察卡维地洛对顺铂致大鼠急性肾衰竭的影响,并初步探讨其作用机制。方法Wistar大鼠给予卡维地洛5,15和30mg.kg-1,ig,每日1次,连续6d,于d3单次ip顺铂10mg.kg-1。于d6测定血清尿素氮(BUN)和肌酐(SCr)含量,尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)活性,肾组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)活性;苏木素-伊红染色观察肾脏病理改变。结果顺铂组大鼠血清BUN和SCr含量升高,尿NAG活性升高,肾组织MDA水平增加,SOD和GSH-Px水平降低,肾脏病理改变明显。预先给予卡维地洛5和15mg.kg-1可明显逆转上述改变,但加大剂量至30mg.kg-1时效应反而降低。结论在一定剂量范围内,卡维地洛可能通过减少活性氧产生,增加抗氧化酶活性而减轻顺铂所致急性肾衰竭。     

卡托普利对甘油诱导的急性肾衰的保护作用及其机制探讨

目的研究卡托普利对甘油诱导的横纹肌溶解性急性肾衰的保护作用及其机制。方法用50%（v/v）的甘油按8mL.kg^-1后肢肌内注射建立急性肾衰的动物模型。所有大鼠单笼饲养,药物处理组每日分别以卡托普利和依那普利灌胃共7d,第7d损伤组和药物处理组禁水24h后注射甘油,注射甘油后饮水不限,24h后处死动物。通过检测血浆晚期氧化蛋白产物（AOPP）水平、肾组织形态学变化、超氧化物歧化酶（SOD）、血管紧张素转换酶（ACE）和谷胱甘肽过氧化物酶（GSH-Px）活性等查明AOPP是否与急性肾衰有关,并阐明卡托普利对其的保护作用及其机制。结果给大鼠后肢肌内注射50%（v/v）的甘油能诱导横纹肌溶解性急性肾衰,降低SOD、GSH-Px的活性和NO浓度,升高血尿素氮（BUN）、肌酐（Cr）浓度、AOPP和脂质过氧化产物（MDA）水平。卡托普利（30mg·kg^-1）能减轻肾损害和改善肾功能,逆转SOD、GSH-Px的活性、NO和AOPP水平的改变,而依那普利（30mg·kg^-1）和低剂量的卡托普利（10mg·kg^-1）保护作用不明显。结论卡托普利（30mg·kg^-1）对横纹肌溶解所致急性肾衰具有明显的保护作用,该作用可能与其抗氧化作用有关,而且可能是巯基依赖性的。     

Protective effects of FK453, a potent nonxanthine adenosine A1 receptor antagonist,on glycerol-induced acute renal failure in rats

The purpose of the present study was to examine the protective effect of FK453, (+)-(R)-1-[(E)-3-(2-phenylpyrazolo [1,5-a] pyridin-3-yl) acryloyl]-2-piperidine ethanol, a potent non-xanthine (adenosine A₁ receptor antagonist, on glycerol-induced acute renal failure (ARF) in rat in comparison with the effects of FR113452 (S-(-) enantiomer of FK453), 1,3-dipropyl-8-cyclopentyl-xanthine (adenosine A₁ receptor antagonist), theophylline (nonselective adenosine receptor antagonist), CGS15943 [1,2,4] triazolo [1,5-C] quinazolone, adenosine A_2A receptor antagonist), and typical diuretics (hydrochlorothiazide and furosemide). FK453 (1 and 10 mg/kg orally) significantly reduced serum creatinine and urea concentrations in 25% glycerol (10 ml/kg intramuscularly)-induced ARF by protective treatment. The effect was similar to that of 1,3-dipropyl-8-cyclopentyl-xanthine and theophylline. FR113452 and CGS15943 had little effect on serum creatinine and urea concentrations. In contrast, hydrochlorothiazide and furosemide increased serum creatinine and urea concentrations. FK453, hydrochlorothiazide, and furosemide did not have any effect on either serum creatinine or urea concentration in 25% glycerol-induced ARF by therapeutic treatment. In 50% glycerol (10 ml/kg im)-induced ARF, FK453 reduced serum creatinine and urea concentrations, and increased urine volume and creatinine clearance. The results of the present study showed that FK453, a potent nonxanthine adenosine A₁ receptor antagonist, ameliorated glycerol-induced ARF in the rat. The findings support the idea that adenosine is an important factor in the development of glycerol-induced ARF in the rat and that the protective effect of adenosine receptor antagonist is mediated via the adenosine A₁ receptor. Drug Dev. Res. 39:47–53 © 1997 Wiley-Liss, Inc.     

Pharmacological investigations of Punica granatum in glycerol-induced acute renal failure in rats

Objective:

The present study was designed to investigate the ameliorative potential and possible mechanism of hydroalcoholic extract of flowers of P. granatum in glycerol-induced acute renal failure (ARF) in rats.

Materials and Methods:

The rats were subjected to rhabdomyolytic ARF by single intramuscular injection of hypertonic glycerol (50% v/v; 8 ml/kg) and the animals were sacrificed after 24 hours of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury.

Results:

Pretreatment with hydroalcoholic extract of flowers of P. granatum (125 and 250 mg/kg p.o. twice daily for 3 days) significantly attenuated hypertonic glycerol-induced renal dysfunction in a dose-dependent manner. BADGE (Bisphenol-A-diglycidyl ether) (30 mg/kg), a peroxisome proliferator-activated receptor (PPAR)-γ antagonist, and N(omega)-nitro-l-arginine-methyl ester (L-NAME) (10, 20, and 40 mg/kg), nitric oxide synthase inhibitor, were employed to explore the mechanism of renoprotective effects of Punica granatum. Administration of BADGE (30 mg/kg) and L-NAME (40 mg/kg) abolished the beneficial effects of P. granatum in glycerol-induced renal dysfunction.

Conclusion:

Hydroalcoholic extract of flowers of P. granatum has ameliorative potential in attenuating myoglobinuric renal failure and its renoprotective effects involve activation of PPAR-γ and nitric oxide-dependent signaling pathway.     

血液透析的不同模式治疗急性肾功能衰竭患者的有效性及对肾功能、电解质的影响

目的 探讨血液透析的不同模式治疗急性肾功能衰竭(ARF)患者的有效性。方法 按随机数字将68例急性肾功能衰竭患者分为两组,即血液透析组和连续性血液净化组,每组34例,血液透析组采用血液透析模式治疗,连续性血液净化组采用连续性血液净化模式治疗,比较两组治疗效果、透析前后的肾功能指标、电解质和pH的异常情况。结果 (1)两组在年龄、性别、病因、ARF严重程度、透析疗程、肌酐、尿量、尿素氮等临床一般资料方面均无显著性差异(P＞0.05);(2)血液透析组治疗的总有效率为73.53%,连续性血液净化组治疗的总有效率为76.47%,两组的治疗总有效率差异无统计学意义(χ²=0.075,P=0.785＞0.05);(3)两组透析前的电解质和pH的异常率均无明显差异(P＞0.05),透析后,两组的电解质和pH的异常率明显降低,差异具有统计学意义(P＜0.05),但连续性血液净化组电解质和pH的异常率明显低于血液透析组,差异具有统计学意义(P＜0.05);(4)多因素分析结果显示,年龄是尿素氮和肌酐的影响因素,性别、透析方法等变量与尿素氮和肌酐无统计学关联;(5)连续性血液净化组的血清肌酐、尿素氮低于血液透析组,但差异无统计学意义(P＞0.05)。结论 血液透析与连续性血液净化方法治疗急性肾功能衰竭的效果较好,均能有效地清除急性肾功能衰竭患者的肌酐、尿素氮,连续性血液净化较血液透析更有效地纠正电解质和pH的异常。     

大蒜素对大鼠急性脑缺血再灌注损伤保护作用的研究

目的　研究大蒜素 (allicin)对局灶性脑缺血再灌注损伤的保护作用及机制。方法　采用线栓法制备大鼠大脑中动脉缺血再灌注模型 ,于缺血 3h再灌注 2 4h后测定大鼠脑组织中超氧化物歧化酶 (SOD)和髓过氧化物酶 (MPO)的活性、丙二醛 (MDA)、谷胱甘肽 (GSH)及血浆中一氧化氮 (NO)含量。结果　大蒜素 10、2 0mg·kg-1能将SOD活性从2 0 5 87± 16 5 2分别提高到 2 5 9 77± 19 6 5和 2 84 5 4±2 1 79,将MDA从 38 6 9± 0 10分别降至 2 8 6 8± 1 37和2 0 97± 0 4 4 ,将GSH含量从 2 8 31± 0 6 4分别提高到36 19± 1 12和 4 7 96± 0 4 4 ,将NO含量从 2 9 7± 0 4 9分别降至 2 7 38± 1 4 6和 2 3 0 0± 0 71,将MPO从 0 2 9±3 0 6× 10 -2 分别降至 0 2 6± 2 13× 10 -2 和 0 2 3± 7 5 2×10 -2 。结论　大蒜素对大鼠局灶性脑缺血再灌注损伤有明显保护作用 ,其机制可能与提高抗氧化酶活性 ,抗脂质过氧化损伤及抗炎作用有关     

川芎嗪防治庆大霉素致急性肾功能衰竭的药理机制研究

腹膜内注射庆大霉素，建立大鼠急性肾功能衰竭的动物模型，观察川芎嗪对急性肾衰的防治效果，并初步探讨了其作用机制。结果表明：川芎嗪可改善实验动物的肾功能，降低肾小管损害，促进肾髓质ＰＧＥ２分泌，升高ＰＧＩ２／ＴＸＡ２比值，减少该模型肾皮质丙二醛含量。提示川芎嗪可能通过影响肾髓质前列腺素分泌而对急性肾衰产生防治作用，还可能与减少肾皮质氧自由基的产生有关。     

褪黑素对大鼠急性脑缺血再灌注损伤保护作用研究

目的　探讨褪黑素 (melatonin ,MT)对急性脑缺血再灌注损伤的保护作用及机制。方法　用线栓法制备大鼠大脑中动脉急性缺血再灌注损伤模型 ,再灌注 2 4h后测定大鼠脑组织中丙二醛 (malondialdehyde ,MDA)含量、超氧化物歧化酶 (superoxidedismutase,SOD)和髓化过氧化物酶(myeloperoxidaseMPO)活性以及血浆中血栓素B2 (throm boxaneB2 ,TXB2 )、6 酮 前列腺素F1α( 6 keto prostaglandinF1α,6 酮 PGF1α)含量。结果　MT 10、2 0mg·kg-1能保护SOD活性、减缓脑组织中MDA的升高 ,2 0mg·kg-1还可恢复血浆中TXB2 与 6 酮 PGF1α的平衡 ,减缓脑组织中MPO的升高。结论　MT对大鼠急性脑缺血再灌注损伤的保护作用与其提高抗氧化酶活性 ,抗脂质过氧化损伤及抗炎作用有关     

连续性肾脏替代疗法在老年重症急性肾衰竭中的临床应用

目的探讨连续性肾脏替代疗法(CRRT)在救治老年重症急性肾衰竭(SARF)中的作用。方法40例老年重症ARF患者应用CRRT治疗,观察治疗前后血尿素氮、肌酐、电解质、动脉血气分析和临床症状的变化。结果与治疗前相比较,血尿素氮、肌酐显著下降(P<0.05)电解质紊乱、酸中毒得到纠正,高血容量状态得到改善,40例患者16例存活,24例死亡,CRRT治疗中血液动力学保持稳定。结论老年重症ARF患者应用CRRT是安全有效的,可延长其生存时间,提高生存质量,改善预后。     

序贯透析治疗肾功能衰竭合并急性左心力衰竭的临床应用

目的观察序贯透析对肾功能衰竭合并心力衰竭、肺水肿患者的治疗效果。方法对13例肾功能衰竭合并急性心力衰竭、肺水肿的患者行序贯透析疗法,观察其临床症状、体征,分析其疗效。结果痊愈7例,显效5例,有效1例,总有效率为100.0%。结论序贯透析能迅速缓解肾功能衰竭合并急性左心力衰竭患者的临床症状,改善患者的心功能状况,是抢救肾功能衰竭合并急性左心力衰竭的有效方法 。