Normal mesenteric lymph ameliorates acute kidney injury following lipopolysaccharide challenge in mice

Background: The kidney is one of the prior damaged organs subjected to severe infection and sepsis shock. Our previous studies have shown that the normal mesenteric lymph (NML) obtained from healthy dogs could alleviate multiple organ injuries following endotoxic shock. In the current study, we further investigated the beneficial effect of NML from healthy mice on acute kidney injury (AKI) induced by lipopolysaccharide (LPS) in mice. Methods: The mice in LPS and LPS?+?NML groups received an intraperitoneal injection of LPS (35?mg/kg). One hour later, the treatment of NML was performed and kept for 6?h. Then, the renal function indices, renal morphology, the levels of phosphorylation mitogen-activated protein kinases (MAPKs), markers of sensitization to LPS, as well as pro-inflammatory mediators in renal tissue were observed. Results: Intraperitoneal injection of LPS induced an increased level of urea in plasma, lipopolysaccharide-binding protein (LBP), cluster of differentiation 14 (CD14), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), but no obvious changes in the MAPKs in renal tissue. NML treatment decreased the levels of urea, CD14, TNF-α and IL-6 in mice after LPS injection. Conclusion: The current results indicate that NML alleviates LPS-induced AKI through its attenuation of sensitization to LPS.     

Urinary markers of acute kidney injury in newborns with perinatal asphyxia*

Background: Acute kidney injury (AKI) affects up to 60% of severely asphyxiated neonates. The diagnosis of AKI can be and is further challenged by a lack of good biomarkers. We studied the role of novel markers for AKI, neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-18), Netrin-1 (NTN-1), and sodium hydrogen exchanger isoform 3 (NHE3) on development and early diagnosis of AKI in newborns with perinatal asphyxia (PA). Methods: Forty-one newborns with a diagnosis of PA (15 with AKI and 26 without AKI) and 20 healthy matched controls were involved to the study. Urinary samples were obtained on postnatal days 1 and 4 for patients with PA and on postnatal day 1 for the control subjects. AKI was defined using a serum creatinine-based modification of the acute kidney injury network criteria. Results: The levels of NGAL, NTN-1, NHE3, and IL-18 on the first postnatal day urine samples were higher in patients compared to controls (p?<?0.001, p?<0.001, p <0.02, p <0.001, respectively). In patients with AKI, the levels of NGAL and IL-18 were higher when compared to patients without AKI (p?=?0.002, p <0.001, respectively). The levels of NTN-1 and NHE3 were similar in both groups. For the samples obtained on postnatal day 4, only NGAL levels were significantly higher in patients with AKI (p?=?0.004) compared to those without AKI. Conclusion: To our knowledge, this is the largest study, which evaluated the utility of urinary biomarkers in the diagnosis of AKI in newborns with PA. First day, urine NGAL and IL-18 levels have an important diagnostic power in such patients.     

Inhibition of Na/H exchanger 1 by cariporide alleviates burn-induced multiple organ injury

Background

Severe burns initiate an inflammatory response characterized by the upregulation of proinflammatory cytokine, which contributes to multiple organ injury. Na⁺/H⁺ exchanger 1 (NHE1) plays a significant role in several inflammatory processes. This study was designed to investigate the role of NHE1 in burn-induced inflammation and multiple organ injury.

Materials and methods

Rats were subjected to a 30% total body surface area full-thickness burn. Cariporide was used to assess the function of NHE1 in burn-induced multiple organ injury by biochemical parameters, histologic changes, and inflammatory cytokine production.

Results

We found that NHE1 expression was significantly increased after burn injury. Inhibition of NHE1 by cariporide attenuated burn-induced edema and tissue injury in heart, lung, kidney, and small intestine. Cariporide also inhibited plasma levels of tumor necrosis factor α, interleukin 6, and myeloperoxidase activity.

Conclusions

These results indicate that NHE1 inhibition prevents burn-induced multiple organ injury. The salutary effects afforded by NHE1 inhibition, at least in part, are mediated by attenuating systemic inflammatory response.     

Kidney injury molecule-1 in kidney disease

Kidney injury molecule-1(KIM-1) is a type I membrane protein, comprising an extracellular portion and a cytoplasmic portion, which is expressed at very low levels in the normal kidney. The extracellular portion can cleave and rapidly enter tubule lumens after kidney injury, and can then be detected in the urine. It has been confirmed that the urine KIM-1 level is closely related to tissue KIM-1 level and correlated with kidney tissue damage. Not only is KIM-1 proven to be an early biomarker of acute kidney injury but it also has a potential role in predicting long-term renal outcome. This review summarizes the relationships between KIM-1 and kidney injury, especially in chronic kidney disease.     

Value of kidney injury molecule -1 in the diagnosis of acute kidney injury: a Meta analysis

Objective To access the early diagnosis value of kidney injury molecule-1 (KIM-1) in patients with acute kidney injury (AKI) by Meta-analysis. Methods Databases MEDLINE, EMBASE, Pubmed, Elsevier Science Direct, Scopus, Web of Science, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and WanFang Data were retrieved to collect the diagnostic tests on KIM-1 for AKI published before July 2013. The literatures were screened independently by two reviewers according to the inclusion and exclusion criteria, the data were extracted, and the methodological quality was assessed. Statistic software Meta-Disc 1.4 and STATA 12.0 were used to conduct analyses. Results Eighteen articles were included in this study with a total of 3 427 patients. The summary for urinary KIM-1 in the diagnosis of AKI were sensitivity 0.67(95%CI: 0.63, 0.70), specificity 0.80 (95%CI: 0.78, 0.81), positive likelihood ratio 3.53(95%CI：2.73, 4.56), negative likelihood ratio 0.30 (95%CI: 0.21, 0.42), diagnostic odds ratio 15.13(95%CI: 8.40, 27.25), and the area under the curve (AUC) of summary receiver operating characteristic curves (SROC) was 0.865 2. Subgroup analysis revealed the sensitivity, specificity and diagnostic odds ratio of urinary KIM-1 measured after 2 to12 h post operation in diagnosis of AKI after cardiac surgery were 0.88(95%CI: 0.81, 0.93), 0.75(95%CI: 0.71, 0.79) and 30.22 (95%CI: 16.19, 56.42), respectively. The AUC of SROC was 0.923 7. Conclusions KIM-1 as a single indicator has moderate accuracy for early diagnosing AKI, especially with a high diagnostic accuracy in AKI after cardiac surgery.     

Role of OMA1 in lipopolysaccharide-induced acute kidney injury

Objective To investigate the role of OMA1 in acute kidney injury (AKI) induced by lipopolysaccharide (LPS). Methods OMA1 wild-type and knocked out mice (8 week old) were injected with 10 mg/kg body weight of LPS. The model was confirmed by testing mouse serum creatinine and blood urea nitrogen. The apoptosis in mouse kidney cortex was examined by TUNEL staining and cleaved caspase 3. In vitro, in humam kidney proximal tubular cells (HK2) were knocked down OMA1 by transfecting OMA1 shRNA, with the scramble shRNA being used as negative control of transfection. HK2 cells were cultured with 5 μg/ml of LPS for 24 hours to induce apoptosis. DAPI staining of cells and caspase-3 activity were applied to test apoptosis. The images of mitochondria in cells were obtained by transfection of mito-green plasmid and OMA1 shRNA. Western blotting was used to exam the OMA1 and Cytochrome C expressions. Results Compared with OMA1 KO mice, LPS induced more severe AKI of WT mice with higher Scr [(97.2±26.5) μmol/L vs (53.0±17.7) μmol/L, P＜0.05] and BUN [(43.3±13.7) mmol/L vs (29.7±7.7) mmol/L, P＜0.05]. Moreover, there were more apoptosis cells in kidney cortex in WT mice than in OMA1 KO mice [(75.4± 26.1)/mm2 vs (38.3± 14.4)/mm2, P＜0.05]. About 46% of OMA1 expressions in HK2 cells were inhibited by OMA1 shRNA transfection (P＜0.05). Further, OMA1 shRNA cells with LPS stimulation had decreased mitochondria fragmentation [(29.8±10.9)% vs (43.2±6.8)% , P＜0.05], Cytochrome C release [(37.0±12.3)% vs (76.0±26.2)%, P＜0.05], and cell apoptosis [(13.2±3.9)% vs (25.0±7.1)%, P＜0.05] as compared with control cells. Conclusion Knockdown of OMA1 alleviated septic AKI through inhibition of cell apoptosis, mitochondria fragmentation, and Cytochrome C release.     

Mitochondrial dysfunction in the process of cisplatin-induced acute kidney injury in mice

Objective To assess the characteristics of different doses of cisplatin-induced acute kidney injury, further to understand mitochondrial dysfunction and its role in acute kidney injury (AKI). Methods Male C57BL/6J mice were first randomly divided into two groups: control group (n＝6) and AKI group (n＝12). Then, AKI group was subsequently divided into other two groups according to different dose of cisplatin (10 mg/kg or 20 mg/kg). AKI group received intraperitoneal injection of cisplatin. All mice were sacrificed after 72 h of injection. Renal biochemical function, renal pathological changes, renal injury markers, kidney mitochondrial function and structural changes were observed. Results (1) After 72 hours of injection, the AKI group performed significant kidney injury changes compared to control group, thereinto 20 mg/kg group was more serious than 10 mg/kg group. With the cisplatin dose increasing, renal function markers such as serum creatinine, urine protein gradually increased. (2)Kidney biopsy showed tubular structural damage, the formation of protein casts, kidney injury molecule-1 (KIM-1) gradually increased(P＜0.05). (3)Electron microscopy found tubular mitochondrial structural damage, mtDNA copy number decreased, the level of peroxisome proliferator-activated receptor -gamma coactivator-1alpha (PGC-1α), ATP synthase β decreased(P＜0.05), and Western blotting manifested cytochrome C was released from mitochondria to the cytoplasm. These data all exhibited significant difference between different groups(P＜0.05). Conclusions Cisplatininduces acute kidney injury in dose-dependent manner. Mitochondrial dysfunction participates in kidney injury, and is also related to the kidney pathological damage.     

丙酮酸乙酯对脓毒症肺损伤大鼠细胞间粘附分子-1的影响

目的研究丙酮酸乙酯对脓毒症肺损伤大鼠细胞间粘附分子1(ICAM1)的影响,探讨丙酮酸乙酯保护大鼠脓毒症肺损伤的作用机制。方法采用盲肠结扎穿孔术复制脓毒症肺损伤动物模型,30只Wistar大鼠随机分为假手术组、脓毒症肺损伤组和丙酮酸乙酯(40mg/kg,腹腔内注射)治疗组,每组10只。所有大鼠12h后活杀,用免疫组织化学方法检测肺组织中ICAM1的分布和表达,用免疫印迹法检测肺组织ICAM1蛋白水平的表达,检测支气管肺泡灌洗液白细胞计数、肺湿/干重比和肺组织髓过氧化物酶(MPOase)活性。结果与脓毒症肺损伤组比较,丙酮酸乙酯治疗组免疫印迹法和免疫组织化学法显示肺组织ICAM1的表达显著降低,肺泡灌洗液白细胞计数、肺湿/干重比和MPOase活性降低(P<0.01)。结论丙酮酸乙酯通过抑制肺组织ICAM1的表达,对脓毒症肺损伤大鼠具有保护作用。     

Curcumin alleviates ischemia reperfusion-induced acute kidney injury through NMDA receptor antagonism in rats

Objective: The present study investigated the role of N-methyl-d-aspartate (NMDA) receptors in curcumin-mediated renoprotection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats.

Methods: Rats were subjected to bilateral renal I/R (40?min I, 24?hours R) to induce AKI. Kidney injury was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium level, fractional excretion of sodium, and macroproteinuria. Oxidative stress in renal tissues was assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione content. Hematoxylin &; eosin staining was done to assess histological changes in renal tissues. Curcumin (30 and 60?mg/kg) was administered one hour before subjecting rats to AKI. In separate groups, NMDA receptor agonists, glutamic acid (200?mg/kg), and spermidine (20?mg/kg) were administered prior to curcumin treatment in rats followed by AKI.

Results: I/R-induced AKI was demonstrated by significant change in plasma and urine parameters along with marked increase in oxidative stress and histological changes in renal tissues that were aggravated with pretreatment of glutamic acid and spermidine in rats. Administration of curcumin resulted in significant protection against AKI. However, glutamic acid and spermidine pretreatments prevented curcumin-mediated renoprotection.

Conclusion: It is concluded that NMDA receptor antagonism significantly contributes towards curcumin-mediated protection against I/R-induced AKI.     

急性肾损伤生物学标志物在心脏外科术后的研究进展

急性肾损伤是心脏外科手术后常见的严重并发症,发病率和病死率均较高.血肌酐及尿量作为急性肾损伤的标志物缺乏敏感性,延误了早期有效的治疗.近年来对于诊断急性肾损伤的生物学标志物方面的研究取得了较大进展,有些指标已逐步进入临床研究阶段,其中包括中性粒细胞明胶酶相关脂质运载蛋白、胱抑素C、肾损伤分子-1、白细胞介素-18等.本文旨在对心脏外科术后急性肾损伤早期生物学标志物基础及临床方面的研究进展作一综述.     

乌司他丁对脓毒症致大鼠急性肾损伤肾功能及尿相关指标的影响

目的探讨乌司他丁（UTI）对盲肠结扎穿孔术（CLP〉所致大鼠脓毒症急性肾损伤（AKI）的保护作用。方法SD健康雄性大鼠55只,按随机化原则分成3组：正常对照组5只、模型组25只、乌司他丁治疗组25只,后两组再随机分为5个时间点（1h、6h、12h、24h、48h）,每组每时间点各5只,采用盲肠结扎穿孔术复制脓毒症模型,乌司他丁治疗组,造模后立即给予乌司他丁10万U／kg,尾静脉注射,分别在各个时间点采血、留尿标本,进行肾功能血肌酐（Scr）、尿素（Urea）,尿肾损伤分子（KIM-1）、白细胞介素-18（IL-18）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）检测分析。结果与模型组相比,乌司他丁治疗组大鼠各时间点Scr、Urea,尿KIM-1、IL-18、NGAL浓度均显著降低,差异均有统计学意义（P〈0．05）。结论乌司他丁对脓毒症所致急性肾损伤具有一定的肾脏保护作用。     

Pyruvate-enriched oral rehydration solution improved intestinal absorption of water and sodium during enteral resuscitation in burns

Aim

To investigate alteration in intestinal absorption during enteral resuscitation with pyruvate-enriched oral rehydration solution (Pyr-ORS) in scalded rats.

Methods

To compare pyruvate-enriched oral rehydration solution (Pyr-ORS) with World Health Organisation oral rehydration solution (WHO-ORS), 120 rats were randomly divided into 6 groups and 2 subgroups. At 1.5 and 4.5 h after a 35% TBSA scald, the intestinal absorption rate, mucosal blood flow (IMBF), Na⁺-K⁺-ATPase activity and aquaporin-1 (AQP-1) expression were determined (n = 10), respectively.

Results

The intestinal Na⁺-K⁺-ATPase activity, AQP-1 expression and IMBF were markedly decreased in scald groups, but they were profoundly preserved by enteral resuscitation with WHO-ORS and further improved significantly with Pyr-ORS at both time points. Na⁺-K+-ATPase activities remained higher in enteral resuscitation with Pyr-ORS (Group SP) than those with WHO-ORS (Group SW) at 4.5 h. AQP-1 and IMBF were significantly greater in Group SP than in Group SW at both time points. Intestinal absorption rates of water and sodium were obviously inhibited in scald groups; however, rates were also significantly preserved in Group SP than in Group SW with an over 20% increment at both time points.

Conclusion

The Pyr-ORS may be superior to the standard WHO-ORS in the promotion of intestinal absorption of water and sodium during enteral resuscitation.     

氨甲酰化促红细胞生成素对慢性肾衰竭合并急性肾损伤大鼠肾脏的保护作用

目的观察氨甲酰化促红细胞生成素(carbamylated erythropoietin, CEPO)对慢性肾脏病(CKD)合并急性肾损伤(AKI)大鼠模型的肾脏保护作用。 方法取健康雄性SD大鼠(450±20 g)39只,随机分为3组,首先制作5/6肾切除大鼠慢性肾衰模型,10 d后确认大鼠慢性肾衰竭模型造模成功。在该慢性肾衰竭模型大鼠双后肢肌肉按照8 ml/kg的剂量注射50%甘油制作合并急性肾损伤模型。第11,12,13天向各组注射：生理盐水(NS)组：腹腔注射生理盐水;促红细胞生成素(EPO)组：按照5 000 U/kg的剂量向大鼠腹腔内注射EPO;CEPO组：按照5 000 U/kg的剂量进行腹腔注射CEPO。在第1,5,10,11,13,17天对大鼠的体重、血压进行检测,同时尾静脉采血对红细胞比容、血肌酐、尿素氮进行检测,留取肾组织进行病理学PAS检测。用SPSS 19.0统计软件对实验数据进行统计学处理,P<0.05被认为差异有统计学意义。 结果与生理盐水注射组比较,CEPO组和EPO组可缓解大鼠体重的减轻幅度(F＝8.19,F＝6.84, P<0.05),可保护大鼠肾功能,降低大鼠血肌酐(F＝5.12, F＝13.72, P<0.05)和血尿素(F＝4.63,F＝12.78, P<0.05)的水平,减轻肾脏小管病理损伤(F＝9.14, F＝12.73, P<0.05),并且CEPO组能显示出更明显的作用(P<0.05),CEPO相对于EPO能够缓解升高红细胞比容的副作用(F＝8.27, P＝0.019)。 结论CEPO对CKD合并AKI模型大鼠能起到明显的肾脏保护作用,并且相对于EPO治疗能降低引起红细胞比容升高的副作用。     

Effect of dietary phosphate on Na+-dependent phosphate cotransporters function and expression in the rat kidney

Background Three types (typeI, II, andIII) of sodium-dependent phosphate cotransporters have recently been isolated and shown to be expressed in the mammalian kidney. Understanding of the functional roles and regulation of each transporter is still fragmented, however. Methods We analyzed the functional roles of each transporter by using antisense oligonucleotides in theXenopus oocytes expression system, and by localization in the proximal tubules of rat kidney using immunohistochemistry. Results Phosphate uptake in brush border membranes was increased by about 2 times in rats fed a low-phosphate, as compared with a high-phosphate, diet. Expression of typeI, II, andIII transporter mRNAs was observed in renal poly(A)⁺RNA, isolated from the rats fed a low-phosphate diet. Phosphate uptake increased about 2.5-fold inXenopus oocytes injected with the poly(A)⁺RNA, compared with those given RNA from rats fed a high-phosphate diet. Hybrid depletion of the typeII sodium-dependent phosphate transporter (NaPi-2), but not of the typeI (rNaPi-1) or typeIII transporters (PiT-1 and PiT-2), significantly decreased phosphate transport activity in oocytes injected with the poly(A)⁺RNA from each experimental group rat kidney. In rats fed the lowphosphate diet, NaPi-2 immunoreactivity increased markedly in the brush border membranes of renal proximal tubular cells, whereas rNaPi-1 protein was not changed. Conclusion This study suggests that the typeII transporter functions mainly as a sodium-dependent phosphate cotransporter, and is regulated by dietary phosphate in the rat kidney.     

Pentoxifylline reduces acute lung injury in chronic endotoxemia

BACKGROUND: Pentoxifylline (PTX) attenuates end-organ injury in models of sepsis and hemorrhage. PTX is thought to act by inhibiting phosphodiesterase, thus increasing cAMP and decreasing tumor necrosis factor-alpha (TNF-alpha) synthesis. The effects of PTX on neutrophil and endothelial cell adhesion molecules and, ultimately, organ injury in a chronic endotoxemia model have not been studied. We hypothesized that continuous infusion of PTX reduces acute lung injury (ALI) caused by chronic lipopolysaccharide (LPS) exposure. MATERIALS AND METHODS: Male Sprague-Dawley rats were given continuous infusion of LPS, PTX + LPS combined, or saline (sham) by implantable pumps. Neutrophil CD11b expression, lung histopathology, lung intercellular adhesion molecule-1 (ICAM-1) expression assessed by immune staining, serum TNF-alpha, serum interleukin-6 (IL-6), and bronchoalveolar lavage (BAL) IL-8 were evaluated at different time points. Lung injury was graded in a blinded fashion from 0 (normal) to 4 (severe) for interstitial inflammation, neutrophil infiltration, congestion, and edema. Total lung injury score (TLIS) was calculated by adding listed categories. White cell count in the peripheral blood and in the BAL was also performed. RESULTS: Animals treated with PTX + LPS showed a significant reduction in lung injury score, a marked decrease in ICAM-1 expression, and a significant decrease in IL-8 levels in the BAL and serum IL-6 levels when compared with LPS-treated animals. CONCLUSIONS: Continuous infusion of PTX reduces ALI caused by chronic endotoxemia. The effect seems to be a result of decreased expression of endothelial and epithelial ICAM-1 and modulation of proinflammatory cytokine synthesis.     

自噬和ASPPs在老年大鼠急性肾损伤早期的表达

目的观察自噬相关蛋白和p53凋亡刺激蛋白(ASPPs)在肾损伤早期的表达变化,初步探讨自噬相关蛋白和ASPPs是否可能成为老年大鼠AKI早期生物标志物。 方法建立顺铂致AKI青年与老年大鼠模型。雄性SD老年大鼠随机分为假手术组(Sham),顺铂模型组,同时设数量匹配的雄性SD青年大鼠为对照;模型组大鼠一次性腹腔注射顺铂4 mg/kg,Sham组相同途径注射生理盐水4 ml/kg;在给药12 h、1 d、3 d、5 d、7 d时检测大鼠Scr、BUN;光镜观察大鼠肾脏病理变化;透射电镜观察大鼠肾小管上皮细胞超微结构变化及自噬体的情况;免疫印迹法检测肾脏组织Beclin 1、溶酶体相关膜蛋白2(LAMP2)、p62、p53及ASPP抑制物(iASPP)和ASPP1表达情况。 结果顺铂诱导12 h后,与Sham组比较,青年与老年大鼠Scr无明显变化(P>0.05);电镜观察到大鼠肾小管上皮细胞自噬体出现而且数量显著增多;老年大鼠肾组织Beclin 1、p62、LAMP-2和p53表达水平明显升高(P<0.05),iASPP表达水平明显降低(P<0.05),并且老年大鼠肾组织Beclin 1、LAMP-2和p53变化时间早于青年大鼠(P<0.05)。 结论自噬和ASPPs在老年大鼠AKI发生早期即可出现,在Scr开始升高前,反应性自噬已经启动。自噬相关蛋白和ASPPs有望成为AKI早期的损伤标志物,可能是AKI早期干预的新靶点,但仍需更深入的研究。     

肿瘤坏死因子α、肾损伤分子1在急性缺血再灌注损伤大鼠肾脏及血清中的表达变化

目的观察肾脏急性缺血再灌注损伤(ischermic reperfusion,I/R)后大鼠肾脏及血清中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、肾损伤分子1(kidney injury molecule-1,Kim-1)的表达变化。方法选取雄性SD大鼠96只,体质量250~300 g,随机分为假手术组(Sham组,n=48),缺血再灌注组(I/R组,n=48),通过夹闭双肾动脉建立大鼠肾脏缺血再灌注模型,各组于术后2h、6 h、12 h、24 h、48 h、72 h每时点随机选取8只大鼠,分别取血及肾皮质标本。全自动生化分析仪检测血清肌酐、尿素氮,酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测血清TNF-α、Kirm-1水平,免疫组织化学检测肾组织TNF-α、Kim-1表达。结果与Sham组血清肌酐、尿素氮水平[(50.8±6.8)μmol/L、(4.7±0.5)mmol/L]比较,I/R组均于I/R损伤后6 h开始升高[血清肌酐I/R 6 h时为(79.6±8.8)μmol/L、尿素氮I/R 6 h时为(9.3±1.6)mmol/L,均P0.05]。ELISA检测结果显示,与Sham组血清TNF-α(843.0±60.5)、Kim-1(453.7±56.4)水平比较,I/R组均于I/R 2 h开始升高[I/R 2 h时血清TNF-α为(944.2±68.3)、Kim-1为(1081.3±126.2),均P0.05],48 h达高峰,但TNF-α于72 h明显下降(3 094.4±230.5),血清Kim-1水平48~72 h保持高值。免疫组织化学检测显示I/R损伤后TNF-α、Kim-1主要表达于肾小管,且均在12 h表达最多。结论血清TNF-α与Kim-1能较早提示急性肾脏损伤,但Kim-1优于TNF-α。     

Mitochondria-targeted peptides prevent on contrast-induced acute kidney injury in the rats with hypercholesterolemia

Abstract

Objective: The objective of this study is to evaluate the effect and mechanism of mitochondria-targeted peptides (MTP131 and SPI20) on contrast-induced acute kidney injury (CI-AKI) in rats with hypercholesterolemia. Method: Forty SD rats were randomly divided into normal diet group (NN, n?=?8) and high cholesterol supplemented dietary group (HN, n?=?32). At the end of 8 weeks, the group HN was divided into four subgroups. All Rats were given injection of either diatrizoate (10?mL/kg) or equal volume of normal saline, the rats pretreated with MTP131 or SPI20 were given injection with MTP131 or SPI 20 (3?mg/kg) by peritoneal cavity for 3 times. Blood, urine and renal tissue samples were prepared to determine biochemical parameters. The renal pathological changes were evaluated by hematoxylin and eosin staining and scored semiquantitatively, The protein expression of renal NOX4 was also measured by Western blotting. Results: In diatrizoate-injected rats, Serum creatinine (Scr), fractional excretion of sodium (FeNa%), fractional excretion of potassium (FeK%), pathological scores, renal malondialdehyde (MDA) content, the NADPH oxidase activity and the expression of NOX4 in kidney tissue were significantly increased (p?<?0.01). In the groups pretreated with MTP131 or SPI20, the levels of Scr, FeNa%, FeK%, MDA content and NADPH oxidase activity in renal tissue decreased (p?<?0.01), the levels of renal super oxygen dehydrogenises and ATPase activity increased (p?<?0.01). The renal injuries induced by contrast media (CM) were alleviated. Conclusion: MTP131 and SPI20 might protect acute kidney injury induced by CM in rats with hypercholesterolemia.     

丙酮酸乙酯对烫伤延迟复苏大鼠肾组织高迁移率族蛋白B1表达和急性肾损伤的影响

目的观察丙酮酸乙酯（EP）对烫伤延迟复苏大鼠肾组织高迁移率族蛋白B1（HMGB1）表达及急性肾损伤的影响。方法采用30％体表面积Ⅲ度烫伤延迟复苏大鼠模型,78只大鼠随机分为假伤组（n=18）、烫伤组（n=30）和EP治疗组（n=30）;采用逆转录聚合酶链反应检测各组大鼠肾组织HMGB1 mRNA表达,蛋白印迹法及免疫组化法检测。肾组织HMGB1蛋白表达;同时测定血尿素氮（BUN）含量并观察。肾组织病理变化。结果与假伤组比较,严重烫伤后。肾组织HMGBl基因／蛋白表达于伤后8～72h显著增强（P〈0．05）,BUN含量在伤后8h及24h显著升高（P〈0．05）。与烫伤组比较,EP治疗组肾组织8、24、72h时HMGBl表达均显著下调,BUN含量在8、24h时亦明显下降（P〈0．05）;光镜下观察烫伤组肾组织炎性细胞浸润,肾小管结构破坏出现浊肿、变性,而EP处理后。肾脏病理改变不同程度地减轻。结论HMGB1作为晚期炎性因子参与了烫伤后。肾组织炎症反应的病理过程,应用EP治疗可有效下凋。肾组织HMGB1表达,并显著减轻烫伤延迟复苏所致的急性肾损伤。