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1.
The present study was undertaken to clarify the pathogenesis of cisplatin-induced acute renal failure at the early stage. Male Sprague-Dawley rats were given an intravenous administration of 10 mg/kg cisplatin. 0.9% saline was infused into them at a rate of 2 ml/h for 3 h, starting with a 2-ml bolus injection before cisplatin administration. 3 h following cisplatin administration, no evident morphological abnormalities were found by both light and electron microscopy; there were also no significant changes in GFR. Thirty min after cisplatin injection, urine sodium and potassium excretion increased by 56% and 260% those of the control animals, respectively. Apparent renal mitochondrial respiration dysfunction was observed in cisplatintreated rats 3 h later; the state 4 respiration increased by 100% and state 3 respiration, respiratory control ratio and carbonyl cyanide p-trifluoromethoxyphenyl hydrazone-uncoupled respiration decreased by 46%, 74% and 47% of the controls, respectively. The present data suggest that mitochondrial dysfunction may be a very early event in cisplatin-induced acute renal failure in rats.  相似文献   

2.
INTRODUCTIONAcuterenalfailure(ARF),usuallyreferredtoasacutetubularnecrosis,isacommonsyndromecharacterizedbyanabruptandsustaineddeclineinglomerularfiltrationwithresultantazotemia,causedbyacuteischemicand/ortoxicinjuries.Itisnotimmediatelyreversiblewhenca…  相似文献   

3.
This study was carried out to elucidate the nephroprotective effects from a mixture of 8 L-amino acids and the possible mechanism of protection by this amino acid mixture. Acute renal failure model was induced by an intravenous administration of 10 mg/kg cisplatin to male Sprague-Dawley rats. A mixture of 8 L-amino acids or 0.9% saline was infused at a rate of 2 ml/h for 3 h, starting with a 2 ml bolus injection before cisplatin administration. Amino acids showed no acute effect on renal morphology. The infusion of a mixture of 8 L-amino acids increased GFR by 85% in control rats. The abnormalities of urine sodium and potassium excretion caused by cisplatin were markedly attenuated by the administration of the amino acid mixture. With the infusion of this amino acid mixture, cisplatin-induced abnormal state 4 respiration returned to control levels and the depressed state 3 respiration, respiratory control ratio and carbonyl cyanide p-trifluoromethoxyphenyl hydrazone-uncoupled respiration were ameliorated remarkably. A mixture of 8 L-amino acids showed marked nephroprotection against cisplatin-induced acute renal failure in rats and might function through augmentation of the cisplatin-injured renal mitochondrial electron transport-oxidative phosphorylation sequence, probably via stabilizing the membrane (including inner mitochondrial membrane) protein tertiary structure. In addition, this amino acid mixture remarkably increased GFR and decreased urine sodium excretion in rats.  相似文献   

4.
目的:探讨两种家兔急性肾功能衰竭(ARF)模型的方法学差异.方法:皮下注射1%HgCl2(1.5ml/kg.bw,H组)、肌肉注射50%甘油(5.6ml/kg.bw、8ml/kg.bw、10ml/kg.bw三种剂量,依次为G1组、G2组、G3组)复制家兔ARF模型,测定24h和48h血清尿素氮(BUN)和肌酐(Cre)水平,观察比较各组模型复制的成功率、存活率及稳定性.结果:G1、G2两组不能成功复制ARF模型;G3组BUN、Cre较H组降低(P<0.05).但G3组的存活率及稳定性均显著高于H组(P<0.05).结论:两种模型复制方法各有优缺点,应根据不同研究目的选择相应的模型.  相似文献   

5.

Background and objective

It has been shown that macrophages play an important role in the development of severe acute pancreatitis (SAP), and eventually lead to multiple organ failure (MOF). Clodronate-liposome selectively depleted macrophages. This study was to investigate the role of renal macrophage infiltration in acute renal injury in rats with SAP and to evaluate the potential of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for diagnosis.

Methods

Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation. SPIO-liposomes and SPIO-clodronate-liposomes were prepared by the thin film method. SAP models were prepared by injection of sodium taurocholate into the subcapsular space of rat pancreas. Sprague-Dawley rats were randomly divided into a control group, SAP plus SPIO-liposome (P) group, and SAP plus SPIO-clodronate-containing liposome (T) group. Kidney injury was evaluated by T2-weighted MRI scan. The levels of serum amylase (SAM), blood urea nitrogen (BUN), and serum creatinine (SCr) were measured by an automated enzymatic method. Serum tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in the pancreas and kidney were observed using hematoxylin and eosin (H&E) staining, while cell apoptosis was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. In addition, the macrophage markers (CD68) of the renal tissue were detected with immunohistochemistry.

Results

The pathological changes in the pancreas and kidneys of rats in the T group were milder than those in the P group. The MRI signal intensity of the kidneys in the P and T groups was significantly lower than that in the control group. There were significant changes in the two experimental groups (P<0.01). The levels of SAM, Bun, SCr, and TNF-α in rats in the P group were higher than those in the control group (P<0.01) and in the T group (P<0.01). The apoptosis of the kidney in the T group was higher than that in the P group at 2 and 6 h (P<0.01).

Conclusions

Clodronate-containing liposomes protected against renal injury in SAP rats, and SPIO can be used as a tracer for MRI examination to detect renal injury in SAP rats. SPIO-aided MRI provided an efficient non-invasive way to monitor the migration of macrophages after renal injury in rats with SAP.  相似文献   

6.
青蒿水煎剂灌胃给药,对正常大白鼠的体温无明显影响,对皮下注射10%干酵母混悬液10ml/kg引起发热大白鼠有明显的解热作用,并有明显的剂量关系.给药后1h体温开始下降.给药组大白鼠发热时程明显缩短.  相似文献   

7.

Objective

The present study aims at determining the stability of a popular type 2 diabetes rat model induced by a high-fat diet combined with a low-dose streptozotocin injection.

Methods

Wistar rats were fed with a high-fat diet for 8 weeks followed by a one-time injection of 25 or 35 mg/kg streptozotocin to induce type 2 diabetes. Then the diabetic rats were fed with regular diet/high-fat diet for 4 weeks. Changes in biochemical parameters were monitored during the 4 weeks.

Results

All the rats developed more severe dyslipidemia and hepatic dysfunction after streptozotocin injection. The features of 35 mg/kg streptozotocin rats more resembled type 1 diabetes with decreased body weight and blood insulin. Rats with 25 mg/kg streptozotocin followed by normal diet feeding showed normalized blood glucose level and pancreatic structure, indicating that normal diet might help recovery from certain symptoms of type 2 diabetes. In comparison, diabetic rats fed with high-fat diet presented decreased but relatively stable blood glucose level, and this was significantly higher than that of the control group (P&gt;0.05).

Conclusions

This model easily recovers with normal diet feeding. A high-fat diet is suggested as the background diet in future pharmacological studies using this model.
  相似文献   

8.
目的:观察戊四氮(PTZ)致痫大鼠海马神经元caspase-3表达以及中药复方AAP的脑保护作用.方法:144只健康成年雄性Wistar大鼠随机分为对照组(CK组)、模型组(PTZ组)、中药大剂量组(AAPl组)、中药中剂量组(AAPm组)、中药小剂量组(AAPs组)和丙戊酸钠组(VPA组);每组各6只.CK组和PTZ组分别给予生理盐水(4mL/kg.d)灌胃;中药各组分别给予中药复方大、中、小剂量(10.26g/kg、5.13g/kg、2.56g/kg)灌胃,每天1次;VPA组腹腔注射VPA(20mg/kg.d).造模第一天,除CK组外,其余各组大鼠均腹腔注射戊四氮(PTZ)75mg/kg,观察记录大鼠行为学变化;于致痫后12h、2d、5d、7d相应时间点取材,制备脑标本;免疫组化检测caspase-3表达.结果:致痫后,除CK组外,其余各组海马区caspase-3阳性表达增强;7天,与PTZ组相比,AAPl组、AAPm组和AAPs组海马CA3区caspase-3阳性表达减弱(P〈0.05).结论:caspase-3参与致痫大鼠海马神经元凋亡过程;AAP能降低caspase-3表达,减少神经元凋亡,有神经保护作用.  相似文献   

9.
目的:观察天麻素对癫痫大鼠海马Caspase-3表达的影响及其脑保护作用。方法:120只健康成年雄性Wistar大鼠随机分为对照组、PTZ(戊四氮)组、VPA(丙戊酸钠)组、Gb(天麻素大剂量)组和Gs(天麻素小剂量)组(n=24)。对照组和PTZ组分别以生理盐水(4mL/kg·d)灌胃;VPA组给予丙戊酸20mg.kg^-1,Gb组和Gs组分别给予天麻素200mg.kg^-1和100mg.kg^-1;每天1次,连续7天。造模第一天,除对照组大鼠外,余者均腹腔注射戊四氮75mg/kg,记录动物行为学变化。于致痫后12h、2d、5d和7d相应时间点取材,制备脑标本,免疫细胞化学术检测caspase-3表达。结果:致痫后12h,P11Z组Caspase-3有微量表达,其余各组几乎无表达;2—7d。PTZ组Caspase-3表达增加。与PTZ组比较,Gb组、Gs组及VPA组Caspase-3阳性表达降低,差异显著(P〈0.05);与VPA组比较,Gb组和Gs组Caspase-3表达无显著差异(P〉0.05)。结论:天麻素能降低致痫大鼠海马神经元Caspase-3表达;可能通过抑制神经元凋亡发挥脑保护作用。  相似文献   

10.
目的观察乙醇对大鼠大脑皮层和纹状体细胞内Ca^2+的影响。方法 雄性Wistar大鼠30只,随机分为对照组,乙醇灌胃后0.5h组,1.5h组,3h组和、5h组(各6只)。实验组用60%(V/V)白酒一次性灌胃(灌胃体积为10ml/kg),对照组用等体积生理盐水灌胃。在各时间点急性分离大脑皮层和纹状体细胞,用Ca^2+敏感荧光指示剂Fluo-3/AM负载,共聚焦显微镜测定细胞内游离Ca^2+结果。染毒后大鼠大脑皮层和纹状体细胞内游离Ca^2+荧光强度均降低(与对照组比较),其中,1.5h组降低有显著差异(P〈0.01,P〈0.05)。结论乙醇产生神经行为毒性可能与大脑皮层和纹状体细胞内Ca^2+尝试降低有关。  相似文献   

11.
目的 观察急性乙醇中毒对大鼠海马、小脑氨基酸类神经递质及行为学改变的影响,以探讨急性乙醇中毒对中枢神经系统损害的机制。方法雄性Wistar大鼠48只,随机分为对照组,饮酒后0.5h组,饮酒后1.0h组,饮酒后1.5h组,饮酒后2.0h组,饮酒后4.0h组;实验组60%(v/v)白酒1次灌胃(灌胃体积10ml/kg),对照组用等量生理盐水灌胃。采用高效液相色谱法和Moms水迷宫法分别检测大鼠小脑和海马中谷氨酸(glutamic acid,Glu)和γ-氨基丁酸(gamma aminobutyric acid,GABA)含量的变化以及逃逸潜伏期(escape latency,EL)的变化。结果实验组大鼠小脑和海马中Glu和GABA含量明显下降(P〈0.01),小脑中Glu和GABA比值在0.5h和2,0h组明显升高(P〈0.01).实验组大鼠在饮酒后逃逸潜伏期(EL)值明显延长(P〈0.01),2.0h组和4.0h组的EL值较其他实验组明显缩短(P〈0.01)。结论急性乙醇中毒引起行为学改变可能与小脑和海马氨基酸类神经递质改变有关。  相似文献   

12.
目的:观察甘油致急性肾功能衰竭(ARF)家兔自由基的变化,探讨自由基损伤在ARF发生中的作用及其意义.方法:30只家兔随机分为两组:50%甘油(10ml/kg.bw)肌肉注射复制家兔ARF模型,等量生理盐水代替甘油作为对照组(n均=15).分别应用改良TBA微量法、黄嘌呤氧化酶法测定血清及肾脏组织匀浆的丙二醛(MDA)水平、超氧化物歧化酶(SOD)活性的变化.结果:ARF组血清及肾脏组织匀浆的MDA水平高于对照组(P<0.01),SOD活性显著低于对照组(P<0.01).结论:自由基损伤在甘油致家兔ARF过程中具有重要作用.  相似文献   

13.
目的:观察急性肾功能衰竭(ARF)家兔心肌匀浆自由基、一氧化氮的变化,探讨心肌损伤的体液机制。方法:60只家兔均分为四组(n=15)。ARF模型1组:皮下注射1%HgCl2(1.3ml/kg.bw);ARF模型2组:肌肉注射50%甘油(10ml/kg.bw);以等量生理盐水代替HgCl2和甘油作为对照1、2组。24h后,所有动物颈总动脉放血备检,并选择固定位置。制备10%心肌匀浆。经Aeroset型全自动生化分析仪测定血清反映肾功能的生化指标。检测心肌匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)及其合酶(NOS)的变化。结果:与相应对照组比较,ARF模型1、2组心匀浆SOD活性下降、MDA含量升高(P〈0.05),ARF模型1、2组心匀浆NO含量增强、NOS及iNOS活性增强(P〈0.05~0.01)。结论:ARF家兔心肌损伤的机制与自由基损伤及NO升高有关。  相似文献   

14.
目的观察黄芪对微循环障碍的影响.方法微循环障碍病人70例,男性47例,女性23例;年龄40~70岁.随机分为两组,治疗组35例,用黄芪注射液30ml+5%葡萄糖200ml,静脉内点滴,一日一次;对照组35例,用川穹嗪200 mg+5%葡萄糖200ml,静脉内点滴,一日一次;2周为一疗程.治疗前后分别查微循环.结果两组治疗后微循环均较治疗前明显改善.结论黄芪能改善微循环的血液流态,减少渗出、出血.黄芪可用于血管病的治疗.  相似文献   

15.
冰片在中风及假手术大鼠体内的药代动力学研究(英文)   总被引:1,自引:0,他引:1  
Objective: This study was designed to investigate the pharmacokinetics of borneol in the pathological conditions of stroke and evaluate the pharmacokinetic differences of borneol caused by stroke after oral administration of borneol and Xingnaojing (XNJ). Methods: The rats were divided into two groups, ischemia-reperfusion (IR) and sham-operated (SO) rats. Each group contained two subgroups: pure borneol and XNJ subgroups. After administration with the same dosages of borneol 162.0 mg/kg, plasma samples were collected. The cerebral ischemia-reperfusion model was created by reversible middle cerebral artery occlusion (MCAO). The blood samples were collected punc- tually after oral administration and a specific gas chromatographic system-flame ionization detector (GC-FID) method was developed and employed to determine the level of borneol in the plasma. The pharmacokinetic parameters were analyzed using non-compartmental methods with Kinetica. Results: After administration of borneol, the maximum plasma concentration (Cmax) and area under the curve (AUC) values in stroke rats significantly increased by 302% and 275%, respectively, compared with the SO rats, and the same phenomenon appeared after administration of XNJ. In the rats with the same physiological conditions, the Cmax and AUC had higher values in the borneol subgroup (P〈0.05). Conclusions: These results suggest that the pathological damages of ischemia-reperfusion have a significant impact on the pharmacokinetic traits of borneol and that there are some components in XNJ inhibiting the absorption of borneol.  相似文献   

16.
It has been reported that Ethaselen shows inhibitory effects on thioredoxin reductase (TrxR) activity and human tumor cell growth. In order to find an efficient way to reverse cisplatin resistance, we investigated the reversal effects of Ethaselen on cisplatin resistance in K562/cisplatin (CDDP) cells that were established by pulse-inducing human erythrocyte leukemic cell line K562, which are fivefold more resistant to cisplatin compared to K562 cells. The morphology and growth showed that the adhesion of K562/CDDP further decreased while the cell volume increased. The proliferation of K562/CDDP is strengthened. The antitumor activities in vitro were assessed by MTT (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and combination index (CI), showing the significant synergic effects of cisplatin and Ethaselen. Focusing on apoptosis, a series of comparisons was made between K562 and K562/CDDP. Cisplatin induced higher reactive oxygen species (ROS) generation in K562 and subsequently induced the formation of mitochondrial permeability transition pores (PTPs). In addition, cisplatin increased the ratio of Bax to Bcl-2 in K562, which can influence the mitochondrial membrane permeability. PTP formation and mitochondrial membrane permeabilization eventually resulted in the release of cytochrome c and activation of the Caspase pathway. However, these effects were not clearly seen in K562/CDDP, which may be the reason for the acquired CDDP resistance. However, Ethaselen can induce a high level of ROS in K562/CDDP by TrxR activity inhibition and increased ratio of Bax to Bcl-2 in K562/CDDP by nuclear factor κB (NF-κB) suppression, which subsequently induces the release of cytochrome c in K562/CDDP. This response is partly responsible for the reversal of the cisplatin resistance in K562/CDDP cells.  相似文献   

17.
虫草多糖对变性血红蛋白诱发的急性肾衰的防治作用研究   总被引:1,自引:0,他引:1  
目的探讨虫草多糖对大鼠静脉注射变性血蛋白诱发的急性肾衰的防治作用。方法将实验动物分为正常组,模型组,虫草多糖高、中、低三个剂量组和阳性组,观察治疗后大鼠的肾功能、血液生化指标、肾病理及肾脏指数的变化。结果虫草多糖组肾功能受损程度明显轻于模型组(P〈0.01),肾脏病理损伤明显减轻,虫草多糖组与模型组比较肾脏指数有极显著差异(P〈0.01)。结论虫草多糖能够防治变性血蛋白诱发的急性肾功能衰竭,其机理可能与改善肾功能、纠正代谢紊乱、促进肾小管的修复与再生等作用有关。  相似文献   

18.
目的:研究复方金银花和茵陈五苓两种注射液对内毒素所致家兔肾衰中肾脏组织结构的保护作用。方法:将重量2.5±0.25kg的健康雄性家兔32只,随机分为对照组、模型组、复方金银花组和茵陈五苓组,每组8只。模型组、复方金银花组、茵陈五苓组家兔一次性静脉注射大肠杆菌O111B4内毒素生理盐水,剂量为100ug/kg。两保护组家兔注射内毒素24h后静脉注射剂量为100ug/kg的中药注射液。模型组家兔静脉注射同容积的生理盐水。对照组家兔静脉注射与内毒素溶液和中药注射剂等体积的生理盐水。静脉注射内毒素及生理盐水后第7h处死。取肾组织标本,Bouns液固定,石蜡切片,HE染色,显微观察并摄影。结果:模型组肾脏肾小体血管球肿胀,有血栓形成,肾小囊壁层内皮细胞脱落,肾小囊腔变小,肾小管内皮细胞脱落。复方金银花组、茵陈五苓组肾脏的肾小体血管球略有肿胀,肾小囊的内皮细胞较完整,肾小囊腔较对照组稍变小。结论:复方金银花与茵陈五苓对家兔因内毒素所致肾衰中肾脏组织结构有确实的保护作用。  相似文献   

19.
Background and objective: Gonadotropin-releasing hormone (GnRH) plays an important role in the regulation of ovarian function and ovarian cancer cell growth. In this study, we determined whether administration of the GnRH agonist (GnRHa), triporelin, prior to cisplatin treatment affects cisplatin and/or prevents cisplatin-induced ovarian damage. Methods: nu/nu mice were injected with ovarian cancer OVCAR-3 cells intraperitoneally. After two weeks, the mice were treated with saline (control), cisplatin, GnRHa, or cisplatin plus GnRHa for four weeks. At the end of the experimental protocol, blood, tumor, ovary, and uterine tissues were resected for hematoxylin and eosin (H&E) staining, immunohistochemical analyses of Ki67, nuclear factor-κB (NF-κB), and caspase-3, transmission electron microscopy of apoptosis, or enzyme-linked immunosorbent assay (ELISA) analyses of anti-Mullerian hormone (AMH). Results: Cisplatin treatment effectively inhibited tumor growth in mice treated with human ovarian cancer cells; however the treatment also induced considerable toxicity. Immunohistochemical analyses showed that Ki67 expression was reduced in cisplatin-treated mice compared to control (P<0.05), but there was no statistically significant differences between cisplatin-treated mice and cisplatin plus GnRHa-treated mice (P>0.05), while expressions of NF-κB and caspase-3 were reduced and induced, respectively, in cisplatin-treated mice and cisplatin plus GnRHa-treated mice. Apoptosis occurred in the GnRHa, cisplatin, and cisplatin plus GnRHa-treated mice, but not in control mice. Ovaries exposed to GnRHa in both GnRHa mice and cisplatin-treated mice (combination group) had significantly more primordial and growth follicles and serum levels of AMH than those in the control mice and cisplatin-treated mice (P<0.05). Conclusions: Administration of GnRHa to mice significantly decreased the extent of ovarian damage induced by cisplatin, but did not affect the anti-tumor activity of cisplatin.  相似文献   

20.
目的观察用不同浓度的乙醇一次性灌胃-1h后大鼠下丘脑、纹状体以及海马内内源性阿片肽即:β-内啡肽(β-endorphine,β-EP),甲硫脑啡肽(met—enkephalin,MENK)、亮脑啡肽(leu—enkephalin,LENK)和强啡肽A(dynorphin A,Dyn A)含量的变化,并记录大鼠血中乙醇浓度及其痛阂的改变,以探讨乙醇的中枢作用机制与内源性阿片肽的关系。方法成年Wistar大鼠随机分为对照组、低浓度组和高浓度组,低浓度组和高浓度组分别用25.6%(v/v)和51.3%(v/v)的乙醇溶液按10ml/kg一次性灌胃,对照组给予等量生理盐水。结果急性摄入乙醇后,低浓度组和高浓度组大鼠痛阂值均升高(P〈0.05或P〈0.01)。与对照组相比,低浓度组大鼠β-EP和MENK的含量在下丘脑内明显增高(P〈0.01或P〈0.05).高浓度组大鼠β-EP,MENK,LENK在下丘脑、纹状体和海马内含量均显著增高(P〈0.01),DynA含量无明显变化(P〉0.05)。结论急性摄入乙醇可引起脑内源性阿片肽含量的增加,这可能是导致乙醇急性灌胃后大鼠痛阈值升高的原因之一。  相似文献   

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