WDR5在大鼠肾脏缺血再灌注损伤中的作用及机制研究

目的:探讨WDR5基因在肾脏缺血再灌注损伤中的作用及机制.方法:成年雄性SD大鼠48只,按照随机数表法分为对照组、缺血再灌注损伤组(IR组)、药物溶剂组(DMSO组)、WDR5-0103低剂量组(1mg/kg)、WDR5-0103中剂量组(5mg/kg)、WDR5-0103高剂量组(25mg/kg).对照组:仅切除大鼠...     

Protective effect of sesamin in lipopolysaccharide-induced mouse model of acute kidney injury via attenuation of oxidative stress,inflammation, and apoptosis

Abstract

Context: Acute kidney injury (AKI) is considered a major public health concern in today’s world. Sepsis‐induced AKI is large as a result of exposure to lipopolysaccharide (LPS) that is the major outer membrane component of Gram‐negative bacteria. Sesamin is the main lignan of sesame seeds with multiple protective effects.

Objective: In this research, we tried to demonstrate the protective effect of sesamin pretreatment in LPS-induced mouse model of AKI.

Methods: LPS was injected at a single dose of 10?mg/kg (i.p.) and sesamin was given p.o. at doses of 25, 50, or 100?mg/kg, one hour prior to LPS.

Results: Treatment of LPS-challenged mice with sesamin reduced serum level of creatinine and blood urea nitrogen (BUN) and returned back renal oxidative stress-related parameters including glutathione (GSH), malondialdehyde (MDA), and activity of catalase and superoxide dismutase (SOD). Moreover, sesamin alleviated inappropriate changes of renal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), tumor necrosis factor α (TNFα), interleukin-6, DNA fragmentation (an apoptotic index), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, sesamin diminished magnitude of kidney tissue damage due to LPS.

Conclusion: In summary, sesamin could dose-dependently abrogate LPS-induced AKI via attenuation of renal oxidative stress, inflammation, and apoptosis.     

Artesunate Inhibits Renal Ischemia Reperfusion-Stimulated Lung Inflammation in Rats by Activating HO-1 Pathway

Artesunate (AS), a semi-synthetic derivative of Artemisia, has been shown to exert a wide range of pharmacological effects, such as anti-inflammatory and antioxidant functions. However, the protective functions of AS on renal ischemia reperfusion injury (RIR)-stimulated lung inflammation remain unclear. In this research, acute lung injury (ALI) was stimulated by renal ischemia reperfusion injury (RIR). AS (15 mg/kg) was intraperitoneal administrated to rat 1 h before RIR stimulation. Serum and pulmonary NO, MDA, IL-6, MIP-2, and PGE₂ levels, arterial blood gas and biochemistry, lung wet/dry weight ratio and MPO activity, total cell number and protein concentration in BALF, tissue histology, and NF-κB expression were determined. The results indicated that serum and pulmonary NO, MDA, IL-6, MIP-2, and PGE₂ levels, lung wet/dry weight ratio and MPO activity, total cell number, and protein concentration in BALF enhanced after RIR stimulation. These alterations were mitigated by AS. AS attenuated lung wet/dry weight ratio and MPO activity, total cell number, and protein concentration in BALF. AS attenuated RIR-stimulated pulmonary NF-κB phosphorylation. In addition, these previously mentioned actions of AS were antagonized by suppressing HO-1 pathway. However, RIR-stimulated arterial blood gas and biochemistry and lung histopathology were also attenuated by AS. In summary, AS inhibited RIR-stimulated lung inflammation by activating HO-1 pathway.     

A novel fibrinogenase from Agkistrodon acutus venom protects against LPS-induced endotoxemia via regulating NF-κB pathway

Abstract

Context: Endotoxins including lipopolysaccharide (LPS) could cause endotoxemia which often results in excessive inflammation, organ dysfunction, sepsis, disseminated intravascular coagulation (DIC) or even death. Previously, a novel fibrinogenase (FII) showed protective effects on LPS-induced DIC via activating protein C and suppressing inflammatory cytokines.

Objective: To evaluate whether FII has protective effect on LPS-induced endotoxemia in mice and learn about the role of NF-κB pathway in TNF-α producing process.

Methods: BALB/C mice were intraperitoneally injected (i.p.) with (a) 30?mg/kg LPS, (b) LPS?+?0.3?mg/kg FII, (c) LPS?+?1.0?mg/kg FII, (d) LPS?+?3.0?mg/kg FII or (e) saline. Both survival rate and organ function were tested, including alanine aminotransferase (ALT), blood urine nitrogen (BUN) and tissue section, and TNF-α was examined by ELISA. RAW 264.7 macrophage was administered with (a) LPS, (b) LPS?+?FII, (c) FII alone or (d) saline, and TNF-α and phosphorylation (P)-NF-κB (P65) were determined by Western blot.

Results: The administration of LPS led to 65% mortality rate, a rise of serum TNF-α, BUN and ALT levels, and both liver and renal tissue damage were observed. While FII treatment significantly increased the survival rate of LPS-induced endotoxemia mice model, histopathology and protein analysis results also revealed that FII remarkably protected liver and renal from LPS damage as well as decreasing TNF-α level. In vitro, FII significantly decreased LPS-induced TNF-α production and the expression of P-NF-κB (P65).

Conclusions: Our findings suggested that FII had protective effect on LPS-induced endotoxemia and organ injuries by suppressing the activation of NF-κB which decreased TNF-α level.     

Sevoflurane pretreatment enhance HIF-2α expression in mice after renal ischemia/reperfusion injury

Ischemia/reperfusion (I/R) injury often occurs, which is one of the major causes of acute kidney injury, thus increasing in-hospital mortality. HIF-2α has a protective role against ischemia of the kidney. Renal ischemia/reperfusion under sevoflurane anesthesia resulted in drastic improvements in renal function. We hypothesized that underlying mechanism responsible for renal protection from sevoflurane pretreatment involves the upregulation of HIF-2α. Sevoflurane pretreatment were performed on WT and HIF-2α knockout mice before renal ischemia/reperfusion. Levels of blood urea nitrogen (BUN) and serum creatinine (Cr) were determined with a standard clinical automatic analyzer. The left kidneys were taken for morphological examination. Expression of HIF-2α in kidney tissue was examined by western blotting. In WT mice, group I/R injury had significantly higher BUN and Cr levels than group control, whereas group I/R + Sev had significantly lower BUN and Cr levels than group I/R injury. Renal HIF-2α expression levels were significantly higher in WT mice of group I/R + Sev than group control and group I/R. In HIF-2α^-/- mice, group I/R + Sev showed much higher BUN and Cr levels and severer histological damage than group I/R and group control. Renal HIF-2α expression levels were significantly higher in WT mice of group I/R + Sev than group control and group I/R. Our findings suggested that HIF-2α might contribute to the beneficial effect of sevoflurane in renal ischemia/reperfusion injury.     

彩色多普勒超声评价肾缺血再灌注后模型兔肾动脉血流动力学变化及与肾功能的关系

背景：既往对肾缺血再灌注损伤诊断主要依靠实验室生化检查及病理检查,彩色多普勒超声仪能无创快速动态显示肾缺血再灌注后肾血流的变化。 目的：运用彩色多普勒超声评价兔肾缺血再灌注后肾动脉血流动力学变化,并探讨其与肾功能指标血尿素氮和血肌酐变化之间的相关性。 方法：随机数字表法将大白兔分为对照组、假手术组、缺血再灌注组。缺血再灌注组肾缺血再灌注模型;假手术组仅行右肾切除;对照组不作手术处理。前两组按照不同时间点再分为3个亚组进行观察。 结果与结论：随着兔肾缺血再灌注损伤加重,各级肾动脉收缩期峰值流速、搏动指数、阻力指数及血清尿素氮和血肌酐逐渐增大,24 h达高峰,叶间动脉最先出现改变血流动力学改变,其中阻力指数是反映肾缺血再灌注损伤程度最敏感指标。提示彩色多普勒超声是一种评价肾缺血再灌注损伤程度的有效方法。     

缺血后处理对缺血再灌注家兔肾皮质血流量的影响

目的:观察缺血后处理(IPo)对缺血再灌注(I/R)家兔肾皮质血流量的影响,探讨IPo的肾保护作用。方法:24只日本大耳白兔随机分成3组:假手术组(S组),I/R组,IPo组,每组8只,均用3%戊巴比妥钠麻醉。I/R组采用结扎并切除右肾,分离并夹闭左肾动脉45min,再灌注60min制备肾I/R模型;S组麻醉后开腹,切除右肾,分离左肾及动脉;IPo组在切除右肾、夹闭左肾动脉45min后,再灌1min,缺血1min,反复4次,再全面恢复血流灌注60min;各组取股动脉血液用去蛋白终点法测定血浆肌酐(Cr)含量,二乙酰-肟显色法测定血尿素氮(BUN)含量;应用激光多普勒血流监测仪观测肾皮质血流量。结果:与S组比较,I/R组血浆Cr和BUN浓度升高(P<0.05),肾皮质血流量显著降低(P<0.05)。与I/R组相比,IPo组血浆Cr和BUN浓度降低(P<0.05),肾皮质血流量升高(P<0.05)。结论:IPo可以增加I/R后肾脏皮质的血液灌流量,改善肾功能。     

Lutein protects against ischemia/reperfusion injury in rat skeletal muscle by modulating oxidative stress and inflammation

Abstract

Background: Lutein is an antioxidant compound with potential biological effects. The present study investigated the protective role of Lutein against I/R injury in skeletal muscle.

Methods: Animals were divided into three groups. Group I – sham operated; Group II- IR injury- Hind limb ischemia was induced by clamping the common femoral artery and vein. After 4?h of ischemia, the clamp was removed and the animals underwent 2?h of reperfusion. Group III-Lutein?+?IR injury- Rats with Lutein treatment received intraperitoneal injection 1?h before reperfusion. The skeletal tissues were analyzed for oxidative stress parameters (reactive oxygen species, protein carbonylation and sulfhydryls, lipid peroxidation). Antioxidant status was determined by evaluating Nrf-2 levels and antioxidant enzyme activities. The inflammatory mechanism was determined through NF-κB and COX-2 expressions. Pro-inflammatory cytokines were determined by ELISA.

Results: The results showed that Lutein treatment significantly decreased the oxidative stress by reducing reactive oxygen species, protein carbonylation and sulphydryls, lipid peroxidation. Further, the levels of Nrf-2 and antioxidant status was significantly declined during IR injury compared to sham operated rats. Lutein treatment reduced the oxidative stress by enhancing Nrf-2 levels and antioxidant status. Skeletal IR injury enhanced the inflammatory signaling by up regulating NF-κB, COX-2 and various pro-inflammatory cytokines. NF-κB, COX-2 expressions were down regulated by Lutein treatment.

Conclusion: The study shows that Lutein protects against skeletal IR injury by down regulating oxidative stress and inflammatory mechanisms.     

IL-13对大鼠急性肾缺血再灌注时IL-1β表达的影响

目的:观察IL-13对急性肾缺血再灌注时IL-1β表达的影响。方法:Wistar雄性大鼠57只,随机分为8组:正常组(normal);假手术组(sham);缺血组:(I)缺血再灌注组(I/R);治疗对照组-1(C-1);治疗对照组-2(C-2);治疗组-1(T-1)和治疗组-2(T-2)。阻断大鼠双侧肾脏血流45min再灌注24h建立急性肾缺血再灌注模型;治疗组分别于阻断血流前、后分别从双侧肾动脉开口注射入1.5μg/50gbw鼠重组白细胞介素13(rmIL-13);检测各组大鼠IL-1β血清水平和肾脏表达,以及肾功能和肾脏病理。结果:(1)治疗组肾脏IL-1β基因(TtoC:P＜0.01)和蛋白表达(T-1toC-1:P＜0.01;T-2toC-2:P＜0.05)明显减少,血清IL-1β水平明显下降;(2)肾功能障碍和肾组织病理变化明显减轻,肾小管损害评分减少(C-1toT-1:45.20±8.64to21.05±8.82,P＜0.01;C-2toT-2:42.25±11.15to23.25±7.31,P＜0.01);(3)血清IL-1β水平与BUN、Cr成正相关(r=0.708,P＜0.01;r=0.770,P＜0.01)。结论:IL-13能有效地抑制大鼠急性肾缺血再灌注损伤IL-1β的表达。     

Immunomodulatory role of recombinant human erythropoietin in acute kidney injury induced by crush syndrome via inhibition of the TLR4/NF-κB signaling pathway in macrophages

Abstract

Objective: The present study aimed to investigate whether recombinant human erythropoietin (rHuEPO) plays an immunomodulatory function by regulating the TLR4/NF-κB signaling pathway.

Materials and methods: C57BL/6 mice were intraperitoneally injected with rHuEPO and, half an hour later, with 50% glycerol at the dose of 7.5?ml/kg to induce crush syndrome (CS)-acute kidney injury (AKI). The levels of TNF-α, IL-1β, IL-6, serum creatinine (Scr), and creatine kinase (CK) were measured. The kidney tissues were analyzed by HE staining, and macrophage infiltration was detected by immunohistochemistry. Double immunofluorescence staining, RT-qPCR, and western blotting were conducted to analyze TLR4/NF-κB p65 expression. Ferrous myoglobin was co-cultured with RAW264.7 cells to mimic crush injury and the production of proinflammatory cytokines. The expression levels of TLR4 and NF-κB p65 were measured.

Results: In vivo study results revealed that rHuEPO ameliorated renal function, tissue damage, production of proinflammatory cytokines, and macrophage infiltration in the kidneys. The protein and mRNA expression levels of genes involved in the TLR4/NF-κB signaling pathway in CS-induced AKI mice were upregulated (p?<?.05). Meanwhile, the expression levels of TLR4, NF-κB p65, and proinflammatory cytokines in RAW264.7 cells were downregulated in CS-AKI mice injected with rHuEPO (p?<?.05).

Conclusions: Our results demonstrated the immunomodulatory capacity of rHuEPO and confirmed that rHuEPO exerts protective effects against CS-induced AKI by regulating the TLR4/NF-κB signaling pathway in macrophages. Therefore, our findings highlight the therapeutic potential of rHuEPO in improving the prognosis of CS-AKI patients.     

右美托咪定抑制肾缺血/再灌注炎性反应

背景：在缺血/再灌注肾脏损伤的防治研究中,用药物激活或抑制机体某些因子从而保护肾组织,对肾移植和移植物的功能恢复有着重要意义。 目的：探索右美托咪定对大鼠肾缺血/再灌注炎性因子及C-X-C型趋化因子受体4表达的影响。 方法：40只大鼠随机等分为假手术组、缺血再灌注组、右美托咪定预处理组及右美托咪定后处理组。后3组行右肾切除,左肾缺血45 min,再灌注60 min,造肾缺血再灌注模型;右美托咪定预处理组于大鼠股静脉穿刺置管后泵注1 μg/kg右美托咪定,10 min后改为0.5 μg/kg,泵注30 min直至缺血即刻;右美托咪定后处理组于左肾再灌注后静脉泵注0.5 μg/kg右美托咪定 30 min。 结果与结论：肾脏缺血再灌注大鼠肾脏损伤严重,炎症明显,肾小管扩张,有肾小球肾炎表现,血清中白细胞介素1β和肿瘤坏死因子α水平显著升高(P < 0.05),血清和肾脏中C-X-C型趋化因子受体4水平也明显增加(P < 0.05);经右美托咪定预处理或后处理的肾缺血再灌注大鼠血清中白细胞介素1和肿瘤坏死因子α水平明显降低(P < 0.05),血清和肾脏中C-X-C型趋化因子受体4水平也明显降低(P < 0.05)。提示肾缺血再灌注可致以炎性反应为特征的肾损伤;右美托咪定可以抑制炎性反应并弱化C-X-C型趋化因子受体4的表达,具有一定的肾保护作用。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

异丙酚通过抑制JAK/STAT通路减轻肝冷缺血再灌注大鼠肾损伤

目的:探讨JAK/STAT信号通路在异丙酚减轻大鼠肝冷缺血再灌注后肾损伤中的作用。方法:SD大鼠随机分为4组(n=8):假手术组(sham组);肝冷缺血再灌注模型组(I/R组);异丙酚组(Pro组),于再灌注前5 min经右侧股静脉给予异丙酚20 mg·kg~(-1)·h~(-1)持续泵注30 min;JAK2抑制剂AG490组(AG490组),于建立模型前30 min腹腔注射AG490 10 mg/kg。再灌注6 h后处死大鼠,采集血样和肾组织标本,检测血清肌酐(Cr)、尿素氮(BUN)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的浓度及肾组织超氧化物歧化酶(SOD)和丙二醛(MDA)的水平;观察肾组织的病理学改变,并进行肾小管损伤评分;检测肾组织细胞凋亡并计算凋亡指数(AI);检测p-JAK2、p-STAT_1和p-STAT_3的蛋白水平。结果:与sham组比较,I/R组血清的Cr和BUN浓度、肾组织的MDA含量、肾小管损伤评分及AI均明显升高,SOD活性降低,p-JAK2、p-STAT_1和p-STAT_3的蛋白水平显著上调(P0.05)。与I/R组相比,Pro组和AG490组的血清BUN和Cr浓度、肾组织的MDA含量、AI和肾小管损伤评分降低,SOD活性升高,p-JAK2、p-STAT_1和p-STAT_3蛋白水平显著下调(P0.05)。结论:异丙酚可减轻肝冷缺血再灌注后肾损伤,其机制可能与抑制JAK/STAT信号通路激活有关。     

远期缺血预适应激活热休克蛋白27、促红细胞生成素、血红素加氧酶1对肾脏缺血再灌注损伤的影响**

背景：缺血再灌注损伤是临床导致急性肾衰竭等其他疾病的重要原因,其机制为多因素、多途径的复杂的病理过程。 目的：观察肾脏进行预处理后激活热休克蛋白、促红细胞生成素和血红素加氧酶1对肾脏缺血再灌注损伤的影响。 方法：雄性C57BL/6小鼠90只随机分成3组。缺血再灌注组为右肾切除,左肾缺血25 min再灌注24 h;预适应组为双侧肾脏缺血20 min再灌注8 d后再进行缺血再灌注。假手术组开腹游离肾蒂。 结果与结论：血清肌酐和尿素氮检测预适应组和假手术组明显低于缺血再灌注组(P < 0.01);MPO染色发现缺血再灌注组大量中性粒细胞浸润(P < 0.01);PAS染色发现预适应组肾组织病理情况轻于缺血再灌注组(P < 0.05);TUNEL染色分析结果表明预适应组和假手术组细胞凋亡数明显少于缺血再灌注组(P < 0.01);预适应组热休克蛋白27 mRNA表达明显高于缺血再灌注和假手术组(P < 0.05),热休克蛋白27 mRNA于第8天时最强,促红细胞生成素、血红素加氧酶1 mRNA在24~    48 h达到峰值A,然后逐渐下降,第8天后达到峰值B,B>A,并且高于假手术组(P < 0.01)。提示远期缺血预适应激活热休克蛋白27、促红细胞生成素、血红素加氧酶1,能减少炎症因子浸润、促进肾小管细胞修复和抑制细胞凋亡从而参与肾脏内源性保护机制。     

Magnesium isoglycyrrhizinate attenuates D-galactosamine/lipopolysaccharides induced acute liver injury of rat via regulation of the p38-MAPK and NF-κB signaling pathways

Context: Acute hepatic failure involves in serious inflammatory responses and leads to a high mortality. Magnesium isoglycyrrhizinate (MgIG), a magnesium salt of 18-α glycyrrhizic acid (GA) stereoisomer, has been shown anti-inflammatory activity previously.

Objective: This study aimed to investigate the protective effects of MgIG, a hepatocyte protective agent, on D-galactosamine and lipopolysaccharide (D-GaIN/LPS)-induced acute liver injury in rats, and meanwhile explore the molecular mechanism.

Materials and methods: Male Sprague–Dawley (SD) rats were injected with D-GaIN/LPS (800?mg/kgBW/10?μg/kgBW) with or without administration of MgIG (225?mg/kg once 6?h after D-GaIN/LPS injection and MgIG 45?mg/kg twice in another 12?h, intraperitoneal injection). Rats were sacrificed 24?h after D-GaIN/LPS injection, the blood and liver samples were collected for future inflammation and hepatotoxicity analyses.

Results: MgIG significantly inhibited D-GaIN/LPS-induced inflammatory cytokines production and hepatotoxicity as indicated by both diagnostic indicators of liver damage [aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels] and histopathological analysis. Western blot analysis demonstrated that MgIG significantly decreased p38-mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation induced by D-GaIN/LPS.

Conclusion: The results indicated that the protective effects of MgIG on D-GaIN/LPS-induced acute liver injury might be correlated with its capacity to regulate the p38-MAPK and NF-κB signaling pathways.     

The effects of the hydroalcohol extract of Rosa canina L. fruit on ischemic acute renal failure in Wistar rats

This research evaluated the possible therapeutic potential of Rosa canina as a preventive agent in ischmia/reperfusiom induced acute renal failure in rats. There were three groups (n?=?10), in which rats received orally 7?days before induction of ischemia, hydroalcoholic extract of R. canina (500?mg/kg) in R. canina?+?ischmia/reperfusiom (I/R) group and distilled water in I/R group. In sham group, the renal arteries were not occluded and distilled was administered orally 7?days before surgery. Renal ischemia was induced by both renal arteries occlusion for 45?min followed by 24?h of reperfusion. Blood samples were collected for biochemical analysis, and finally both kidneys were preserved for future histological examination. R. canina treatment reduced total renal histopathological score as well plasma creatinine and blood urea nitrogen levels in R. canina?+?I/R group in comparison to I/R group. According to these results, R. canina can be useful as a preventive agent against renal damages induced by ischemia/reperfusion injury in rat.     

Protective effect of cinnamicaldehyde in endotoxin poisoning mice

Context: Several pharmacological studies have shown that cinnamicaldehyde (CA) has anti-inflammatory and anti-tumor effects, but no data show the effects of CA on the endotoxin poisoning.

Objective: In this work, the protective effect of CA in LPS-induced endotoxin poisoning mice was investigated.

Materials and methods: Mice were randomly divided into normal, LPS, LPS +5?mg/kg dexamethasone (DEX), LPS +0.132?g/kg CA, and LPS +0.264?g/kg CA group. Pretreated with CA (0.132 and 0.264?g/kg/day, respectively) for 5 consecutive days before LPS injection. Except the normal group, the other animals were intraperitoneally injected with LPS (15?mg/kg).

Results: Twelve hours after LPS injection, CA significantly reduced the production of pro-inflammatory cytokines (interleukin-18, interleukin-1β, and interleukin-5) and chemokines (macrophage colony stimulating factor, macrophage inflammatory protein-1β) in serum. In addition, the histopathological study indicated that CA attenuates lung injury induced by LPS. Moreover, the numbers of neutrophils were significant decreased and the NF-κB (p65) mRNA level was reduced in lung after treated with CA.

Conclusion: The present data suggest that cinnamicaldehyde can be considered as potential therapeutic candidates for the endotoxin-poisoning-related diseases such as sepsis via its anti-inflammation effects.     

Relationship between neutrophil-mediated oxidative injury during acute experimental pyelonephritis and chronic renal scarring.

Previous experiments with rats have suggested that pyelonephritic scarring after acute ascending Escherichia coli pyelonephritis partly results from excessive polymorphonuclear leukocyte (PMN) infiltration and activation in the kidney parenchyma. We have studied the role of PMN oxidative metabolism in generating tissue injury during acute pyelonephritis. Rats with acute pyelonephritis were treated with dapsone (25 mg/kg twice daily for 3 days), a compound known to prevent PMN oxidant damage. In vitro, levels of dapsone easily achieved in vivo inhibited myeloperoxidase (MPO)-mediated reactions involving the oxidation of halides to reactive cytotoxic hypohalites (such as MPO-mediated iodination and luminol-enhanced chemiluminescence). In contrast, dapsone had no effect on superoxide production, lysosomal enzyme release, or bacterial killing by activated PMN. In vivo, dapsone treatment had no significant effect on acute pyelonephritis with respect to (i) bacterial counts, (ii) inflammatory swelling, and (iii) PMN infiltration. However, dapsone-treated animals sacrificed 2 months after acute pyelonephritis had a 65% reduction of renal scars when compared with controls. Since dapsone had no antibacterial effect, this protection is compatible with the hypothesis that dapsone prevented oxidant-generated tissue injury due to the extracellular release of the MPO system by activated PMN during acute suppurative pyelonephritis.     

灯盏细辛对肺缺血-再灌注损伤时核转录因子-κB表达的影响

目的：探讨灯盏细辛对肺缺血-再灌注（I/R）损伤时核转录因子-κB（NF-κB）表达的影响。方法: 建立大鼠在体肺原位I/R损伤模型，将32只大鼠随机分为假手术组（I组）、缺血-再灌注组（II组）、小剂量灯盏细辛组（25 mg/kg,III组）、大剂量灯盏细辛组（50 mg/kg,IV组）；观察各组肺湿干重比（W/D），检测各组肺组织髓质过氧化物酶（MPO）活性，应用免疫组化及Western blotting法检测肺细胞核内NF-κB活性及含量，光镜下HE染色观察病理形态学改变、电镜观察肺组织超微结构变化。结果: III、IV组W/D、MPO活性及细胞核内NF-κB含量均明显低于II组，肺水肿程度及肺超微结构损害显著轻于II组；III、IV组之间比较差异显著（P<0.05）。结论: 灯盏细辛对肺缺血-再灌注损伤具有防治作用，其机制可能与其抑制NF-κB活化，从而减少中性粒细胞浸润、抑制炎症损伤有关。     

Increased dietary sodium induces COX2 expression by activating NFκB in renal medullary interstitial cells

High salt diet induces renal medullary cyclooxygenase 2 (COX2) expression. Selective blockade of renal medullary COX2 activity in rats causes salt-sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8 % NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6 J mice. Co-immunofluorescence using a COX2 antibody and antibodies against aquaporin-2, ClC-K, aquaporin-1, and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a sevenfold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of enhanced green fluorescent protein (EGFP) expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet-fed C57Bl/6 J mice with selective IκB kinase inhibitor IMD-0354 (8 mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary prostaglandin E₂ (PGE₂). These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE₂ synthesis in response to increased dietary sodium.