基因重组可溶性补体受体Ⅰ型对大鼠脊髓损伤组织C9和Clusterin表达的影响

目的 探讨基因重组可溶性补体受体Ⅰ型(sCR1)对大鼠急性脊髓损伤组织补体固有成分C9及补体调节因子Clusterin表达的影响。方法 采用改良Allen重物打击法制成SD大鼠急性脊髓损伤模型，观察sCR1组与生理盐水(NS)组在伤后12h、1、3、7、14d时间点脊髓损伤组织中C9和Clusterin表达的部位及时程，并采用斜板实验评定两组大鼠的下肢运动功能，比较组间差异。结果 sCR1组及NS组在伤后各个时间点脊髓损伤组织中C9、CLusterin表达增强，并存在动态变化过程。sCR1组在伤后各个时间点C9表达均明显轻于NS组(P＜0，01)；sCR1组在伤后12h、1、3d时间点Clusterin表达明显轻于NS组(分别为P＜0．01、P＜0．01、P＜0，05)，伤后7、14d两组间差异无统计学意义。sCR1组在伤后3、7、14d时间点大鼠下肢运动功能明显优于NS组(分别为P＜O．05、P＜O，01、P＜O，01)。结论 基因重组sCR1可显著抑制大鼠急性脊髓损伤组织C9和Clusterin的表达，可通过抑制补体系统激活机制减轻继发性脊髓损伤。     

重组sCR1对大鼠急性脊髓损伤组织免疫炎症反应的影响

目的探讨重组可溶性补体受体Ⅰ型(sCR1)对大鼠急性脊髓损伤组织免疫炎症反应的影响及对脊髓损伤的保护作用。方法采用改良Allen重物打击法制成SD大鼠脊髓急性损伤模型,观察伤后12h、1d、3d、7d、14d时间点sCR1组与生理盐水(NS)组脊髓损伤组织中性粒细胞浸润程度及C3c的阳性表达,测定髓过氧化物酶(MPO)活性,并采用BBB评分法评定大鼠后肢运动功能。结果sCR1组在伤后各时间点C3c阳性表达均明显少于NS组,差异有极显著性意义(P<0.01);sCR1组在伤后各时间点损伤组织髓过氧化物酶(MPO)活性弱于NS组,差异有极显著性意义(P<0.01);sCR1组在伤后7、14d时间点大鼠后肢BBB评分明显优于NS组(P<0.05、P<0.01)。结论重组sCR1可通过抑制补体系统激活机制显著减轻急性脊髓损伤组织的免疫炎症反应,减轻继发性脊髓损伤。     

环孢霉素A对大鼠脊髓损伤早期环氧化酶-2与肿瘤坏死因子α表达的影响

目的:观察环孢霉素A(CsA)对大鼠脊髓损伤(SCI)早期环氧化酶-2(Cox-2)与肿瘤坏死因子α(TNF-α)表达的影响,探讨CsA对大鼠SCI的作用。方法:180只大鼠随机分成对照组、损伤组和损伤后CsA治疗组(治疗组),每组60只。用25g.cm致伤损伤组和治疗组大鼠T8~T11脊髓,对照组不损伤脊髓。治疗组于术后1h予尾静脉注射CsA(2.5mg/kg),之后每隔12h给药1次,对照组和损伤组在相同时间点尾静脉注射相同体积生理盐水。损伤组和治疗组于术后2h、6h、12h、24h、48h和72h处死动物取损伤段脊髓标本,对照组在相应时间点取相应节段脊髓标本,切片后分别行HE染色观察脊髓组织损伤情况、免疫组织化学EnVision法检测TNF-α、免疫组织化学SP法检测Cox-2,并对TNF-α和Cox-2进行定量分析。结果:对照组各时间点脊髓无出血、水肿等变化。损伤组和治疗组伤后2h、6h脊髓灰质可见水肿、出血,但无坏死,周围白质无明显改变;12h、24h脊髓灰质出现广泛灶性出血及出血后形成囊腔,神经元肿胀,部分细胞核浓缩,染色增强,白质见少量红细胞渗出,髓鞘轻度肿胀;48h、72h脊髓灰质中出现神经元固缩、坏死、溶解,细胞体积变小,有大量小胶质细胞增生和中性粒细胞浸润,白质中可见较多红细胞渗出,髓鞘肿胀和大量空泡,周围有炎性细胞浸润和胶质细胞增生;治疗组各时间点的病理改变均较损伤组轻。对照组大鼠脊髓Cox-2呈可疑阳性表达;损伤组和治疗组伤后2h Cox-2即有表达,6h达到高峰,之后逐渐下降;损伤组在伤后72h Cox-2表达仍较对照组高(P<0.05),而治疗组到伤后48h即恢复到对照组水平(P>0.05),治疗组各时间点Cox-2表达均较损伤组低(P<0.05);对照组大鼠脊髓TNF-α呈可疑阳性或弱阳性表达;损伤组和治疗组伤后2h即有TNF-α表达,12h达到高峰,之后逐渐下降;损伤组在伤后72h TNF-α表达仍较对照组高(P<0.05),而治疗组在伤后72h即恢复到对照组水平(P>0.05),治疗组各时间点TNF-α表达均较损伤组低(P<0.05)。结论:CsA能显著降低大鼠SCI后早期损伤脊髓组织中Cox-2和TNF-α的表达,从而减轻脊髓继发性损伤。     

猪皮肤撕脱伤CD18的表达与组织继发性坏死的研究

目的:研究猪皮肤撕脱伤组织中整合素CD18的表达及中性粒细胞的趋化,探讨CD18在皮肤撕脱伤组织继发性坏死中的作用。方法:复制猪皮肤撕脱伤模型,采用RT-PCR方法检测伤后不同时间撕脱组织中CD18mRNA的表达;用髓过氧化酶(Myel operoxi daBe enzyme,MPO)法测定组织中中性粒细胞数量,研究伤后撕脱组织中中性粒细胞的趋化情况。结果:①伤后撕脱组织中CD18mRNA的表达逐渐升高,12h达峰值,24h后有所下降,受伤2h后各时间点实验组CD18mRNA的表达明显高于对照组(P<0.05)。②MPO伤后2h开始升高,12h达峰值,24h无明显下降趋势,受伤2h后实验组各时间点MPO活性明显高于对照组(P<0.01)。结论:皮肤撕脱伤伤后早期组织中整合素CD18呈高表达,其变化与组织中中性粒细胞的趋化呈正相关,提示CD18在皮肤撕脱伤早期组织继发性坏死中可能发挥了重要作用。     

FTY720对大鼠急性脊髓损伤后神经功能恢复的影响及相关机制

目的:观察FTY720对大鼠急性脊髓损伤(ASCI)后神经功能的影响,并探讨其相关机制。方法:168只雌性SD大鼠,随机分成A、B、C三组,每组56只,A组(假手术组)大鼠麻醉后仅切除T9椎板,不打击脊髓,缝合后立即以0.3ml生理盐水灌胃。B、C组采用Allen′s法制作T9脊髓损伤模型,B组(对照组)以0.3ml生理盐水灌胃,C组(治疗组)以FTY720按3mg/kg生理盐水稀释至0.3ml灌胃。每组取8只大鼠分别于术后1d、3d、7d、14d、21d行斜板试验及BBB评分。分别于术后6h、12h、24h、48h、72h、7d、21d处死大鼠,每个时间点每组8只,取损伤段(A组取相应部位)脊髓行超薄切片,HE染色观察各组脊髓坏死情况、炎细胞浸润情况、胶质瘢痕形成情况及脊髓空洞大小,并计数各组术后12h淋巴细胞数、术后12h与72h炎性细胞、术后7d胶质瘢痕区细胞,计算伤后21d脊髓空洞面积与脊髓面积比值;取术后6h、12h、24h、72h的切片行SP免疫组化染色观察caspase-3表达及Tunel染色观察细胞凋亡情况,计算相应时间点免疫组化染色阳性细胞比值和凋亡指数。所有数据以SPSS 13.0进行统计学分析。结果:B、C两组各时间点斜板实验及BBB评分均较A组同时间点差(P<0.05),在术后1d时B、C组之间无显著性差异(P>0.05),术后3d、7d、14d、21d时C组优于B组(P<0.05)。HE染色结果显示A组各时间点脊髓形态正常;B、C组脊髓术后6h可见脊髓内出血、血肿形成,术后12h~48h脊髓进行性水肿、损伤中心区出现液化坏死,伴有炎细胞浸润,以中性粒细胞、淋巴细胞、单核细胞为主,至术后72h,损伤中心区形成无组织结构空洞,空洞周围有大量炎细胞浸润,以小胶质细胞/单核细胞为主;术后12h及72h,B组炎细胞浸润程度明显重于C组(P<0.05),术后12h C组淋巴细胞浸润程度相对B组明显减少(P<0.05),术后7d,脊髓水肿减轻,空洞周围形成胶质瘢痕,胶质瘢痕细胞计数B组明显大于C组(P<0.05),术后21d脊髓空洞形成,脊髓空洞比值B组明显大于C组(P<0.05)。SP免疫组化染色和Tunel染色结果显示A组各时间点几乎见不到caspase-3和细胞凋亡表达阳性细胞,B、C组脊髓损术后6h即可见凋亡细胞,到术后24h达高峰,而后随术后时间延长而逐渐减弱,但是仍然保持在较高水平;caspase-3表达与细胞凋亡同步,各时间点C组caspase-3表达阳性细胞比值和细胞凋亡指数均显著低于B组(P<0.05)。结论:FTY720可以显著改善大鼠ASCI后神经功能,其可能是通过抑制脊髓损伤后的炎症反应,减少caspase-3的表达及神经细胞凋亡,从而减轻脊髓继发性损伤。     

中性粒细胞在急性脊髓损伤中作用的实验研究

目的：观察中性粒细胞在脊髓压迫伤中的局部聚集情况及其可能的作用。方法：采用压迫法致大鼠脊髓中度损伤，实验动物分正常大鼠损伤组、低白细胞血症大鼠损伤组和假手术组。观察伤后1、3、6、12、24h伤段脊髓髓过氧化物酶(MPO)活性，记录双下肢运动诱发电位(MEP)，应用斜板试验评价大鼠的运动功能。结果：脊髓压迫伤后1h MPO活性开始升高，3h达到高峰。低白细胞血症组伤后3hMPO活性较对照组明显降低，脊髓运动功能的改善较对照组明显。结论：脊髓损伤后局部中性粒细胞聚集增加，可能参与脊髓继发性损伤。     

盐酸戊乙奎醚对脓毒症大鼠肺组织炎性反应的影响

目的 探讨盐酸戊乙奎醚对脓毒症大鼠肺组织炎性反应的影响.方法 雄性SD大鼠96只,随机分为4组(n=24):假手术组(S组)、盲肠结扎穿孔组(CLP组)、小剂量盐酸戊乙奎醚组(PH1组)和大剂量盐酸戊乙奎醚组(PH2组).PH1组和PH2组于CLP后即刻分别经尾静脉注射盐酸戊乙奎醚0.1、0.3 mg/kg(用生理盐水稀释至1 ml/kg),S组和CLP组分别给予等容量生理盐水.分别于CLP后3、6、12和24 h(每个时点6只大鼠)经左心室采血,测定血浆中性粒细胞CD11b表达,采血后处死大鼠,观察肺组织中性粒细胞浸润及病理学结果,测定肺组织肿瘤坏死因子-α(TNF-α)含量,CLP后6 h时测定肺组织NF-κB表达及肺血管内皮细胞(PVEC)ICAM-1表达.结果 与S组比较,CLP组、PH1组和PH2组肺组织中性粒细胞计数、TNF-α含量、NF-κB和PVEC ICAM-1表达升高,CLP组及PH1组血浆中性粒细胞CD11b表达升高(P＜0.05或0.01);与CLP组比较,PH1组和PH2组肺组织中性粒细胞计数、TNF-α含量、NF-κB及PVEC ICAM-1表达及血浆中性粒细胞CD11b表达降低(P＜0.05或0.01);与PH1组比较,PH2组肺组织NF-κB、PVEC ICAM-1表达及血浆中性粒细胞CD11b表达降低(P＜0.05或0.01).结论 盐酸戊乙奎醚可通过降低肺组织NF-κB、TNF-α和PVEC ICAM-1水平,下调血浆中性粒细胞CD11b表达,减少肺组织中性粒细胞的浸润,减轻了脓毒症大鼠肺损伤.     

CD44在大鼠急性颈脊髓损伤后肺水肿中的作用

[目的]探讨大鼠急性颈脊髓损伤后不同时间节点血清及肺泡灌洗液中CD44含量的变化与肺水肿的关系.[方法]成年Wistar大鼠40只,体重240 ～ 250 g,雌雄不限.大鼠随机分为实验组和对照组,每组20只,每组又分为造模后24 h、3d、1、2周共4个时间点,每个时间点5只大鼠.实验组采用C7段脊髓改良Allen’s打击法制作大鼠脊髓损伤模型,打击力度为10×2.5 g·cm;对照组只暴露C7脊髓.在不同时间点处死大鼠,检测各时间点两组大鼠血清和肺泡灌洗液中CD44含量和蛋白浓度,计算肺通透指数.[结果]急性脊髓损伤大鼠伤后肺泡灌洗液的CD44无明显变化,血清CD44含量于伤后24 h开始下降,伤后3d达最低值,伤后1周含量开始回升,伤后24 h和3d实验组大鼠血清CD44含量与假手术组有显著差异性.CD44含量变化周期与SCI后肺水肿及肺病理变化周期呈负相关.[结论]血清CD44含量变化周期与SCI后肺水肿及肺病理变化周期呈负相关,急性脊髓损伤后肺水肿的形成过程可能与SCI后血清CD44含量下降有关.     

重组人促红细胞生成素对大鼠脊髓损伤后肿瘤坏死因子-α表达的影响

目的 :探讨重组人促红细胞生成素 (rHuEPO)对大鼠脊髓损伤后肿瘤坏死因子 α (TNF α)表达的影响。方法 :SD大鼠 10 2只 ,随机分为 4组 :假手术组 ;脊髓损伤组 ;脊髓损伤 生理盐水 (NS)治疗组 ;脊髓损伤 rHuEPO治疗组。采用改良Allen’s脊髓损伤打击模型 ,以逆转录 聚合酶链反应 (RT PCR)法测定伤段脊髓组织TNF αmRNA的表达情况。结果 :TNF αmRNA在无损伤脊髓中即见有表达 ,脊髓损伤后 1h表达明显上调并达高峰 ;高表达持续至损伤后 2 4h ;rHuEPO治疗组脊髓伤后 6、 12、 2 4hTNF αmRNA表达明显低于NS治疗组。结论 :rHuEPO能明显抑制大鼠脊髓损伤后TNF αmRNA的表达。     

重组人促红细胞生成素对大鼠脊髓损伤后中性粒细胞趋化因子表达的影响及意义

目的 探讨重组人促红细胞生成素(rHuEP())对大鼠脊髓损伤后中性粒细胞趋化因子(CINC-1)表达的影响。方法 SD大鼠102只,随机分为4组,采用改良Allen’s脊髓损伤打击模型,以逆转录一聚合酶链反应(RT-PCR)法测定伤段脊髓组织CINC-1mRNA的表达情况。结果 正常脊髓组织内存在CINC-1mRNA的表达,脊髓损伤后CINC-1mRNA表达迅速增高,伤后6h达到高峰;rHuEPO治疗组脊髓损伤后6、12小时CINC-1mRNA表达明显低于NS治疗组.结论 CINC-1参与继发性脊髓损伤过程,rHuEPO抑制脊髓损伤后CINC-1mRNA的表达,对脊髓继发性损伤可能有保护作用,、     

Effects of recombinant sCR1 on the immune inflammatory reaction in acute spinal cord injury tissue of rats

cutespinalcordinjuryisaseverekindoftrauma.Thesecondaryinjurymechanismhasbeentoocomplextobetotallyunderstoodtillnow .Studieshaveshownthattheimmuneinflammatoryreactionparticipatesinsecondaryspinalcordinjuryasanimportantpathologicalprocessinearlyinjury .Itwa…     

Effects of recombinant sCRl on the immune inflammatory reaction in acute spinal cord injury tissue of rats

OBJECTIVE: To determine the effects of recombinant soluble complement receptor type I (sCR1) on the immune inflammatory reaction in acute spinal cord injury tissue of rats and its protective effects. METHODS: SD rat models of acute spinal cord injury were prepared by modified Allen's method. The motor function of the rat lower extremities in sCR1 group and normal saline (NS) group was evaluated by the tiltboard experiment at 12 h, 1 d, 3 d, 7 d, and 14 d. The neutrophil infiltration and C3c positive expression were observed. The myeloperoxidase activity was assessed in the injury tissue at 12 h, 1 d, 3 d, 7 d, and 14 d after injury in the two groups. RESULTS: The motor function of rat in sCR1 group at 3 d, 7 d, and 14 d was obviously better than that in NS group (P<0.01, P<0.01, P<0.01). C3c positive expression in sCR1 group at each time point after injury was obviously less than that in NS group (P<0.01). The myeloperoxidase activity in sCR1 group at each time point after injury was obviously less than that in NS group (P<0.01). CONCLUSIONS: Recombinant soluble complement receptor type I (sCR1) can lessen the immune inflammatory reaction in acute spinal cord injury tissue and relieve secondary spinal cord injury by inhibiting the activation of the complement system.     

Activation of complement pathways after contusion-induced spinal cord injury

Previous studies have shown that a cellular inflammatory response is initiated, and inflammatory cytokines are synthesized, following experimental spinal cord injury (SCI). In the present study, we tested the hypothesis that the complement cascade, a major component of both the innate and adaptive immune response, is also activated following experimental SCI. We investigated the pathways, cellular localization, timecourse, and degree of complement activation in rat spinal cord following acute contusion-induced SCI using the New York University (NYU) weight drop impactor. Mild and severe injuries (12.5 and 50 mm drop heights) at 1, 7, and 42 days post injury time points were evaluated. Classical (C1q and C4), alternative (Factor B) and terminal (C5b-9) complement pathways were strongly activated within 1 day of SCI. Complement protein immunoreactivity was predominantly found in cell types vulnerable to degeneration, neurons and oligodendrocytes, and was not generally observed in inflammatory or astroglial cells. Surprisingly, immunoreactivity for complement proteins was also evident 6 weeks after injury, and complement activation was observed as far as 20 mm rostral to the site of injury. Axonal staining by C1q and Factor B was also observed, suggesting a potential role for the complement cascade in demyelination or axonal degeneration. These data support the hypothesis that complement activation plays a role in SCI.     

髓鞘相关蛋白抗体对大鼠脊髓损伤早期bcl-2与bax表达的影响

目的 探讨髓鞘相关蛋白(Nogo-A)抗体应用于脊髓损伤动物模型中对bcl-2与bax表达的影响.方法 建立大鼠急性脊髓损伤实验动物模型.180只大鼠随机分成对照组、损伤组和损伤后Nogo-A抗体治疗组,每组各60只.不同时间点损伤节段脊髓取材,分别行苏木素-伊红(HE)染色、免疫组织化学法检测bcl-2、bax表达并进行定量分析.结果 HE染色后光镜下观察:损伤后治疗组出血、小胶质细胞增生和炎细胞浸润均较损伤组轻.bcl-2、bax在损伤组和治疗组表达呈现动态变化,损伤后24 h bcl-2表达达高峰(3组分别为0.1004±0.0091、0.1890±0.0100、0.2456±0.0179,F=197.541,P＜0.01);损伤后8 h bax表达达高峰(3组分别为0.1084±0.0041、0.3440±0.0070、0.2472±0.0071,F=1856.199,P＜0.01);3组各时间点的图像分析结果 经单因素方差分析,差异有统计学意义(P＜0.05),治疗组和损伤组比较,bcl-2表达增强而bax表达减弱.结论 Nogo-A抗体治疗脊髓损伤能抑制bax表达,促进bcl-2表达,减轻脊髓继发性损伤.     

CD11d Antibody Treatment Improves Recovery in Spinal Cord-Injured Mice

Acute administration of a monoclonal antibody (mAb) raised against the CD11d subunit of the leukocyte CD11d/CD18 integrin after spinal cord injury (SCI) in the rat greatly improves neurological outcomes. This has been chiefly attributed to the reduced infiltration of neutrophils into the injured spinal cord in treated rats. More recently, treating spinal cord-injured mice with a Ly-6G neutrophil-depleting antibody was demonstrated to impair neurological recovery. These disparate results could be due to different mechanisms of action utilized by the two antibodies, or due to differences in the inflammatory responses between mouse and rat that are triggered by SCI. To address whether the anti-CD11d treatment would be effective in mice, a CD11d mAb (205C) or a control mAb (1B7) was administered intravenously at 2, 24, and 48?h after an 8-g clip compression injury at the fourth thoracic spinal segment. The anti-CD11d treatment reduced neutrophil infiltration into the injured mouse spinal cord and was associated with increased white matter sparing and reductions in myeloperoxidase (MPO) activity, reactive oxygen species, lipid peroxidation, and scar formation. These improvements in the injured spinal cord microenvironment were accompanied by increased serotonin (5-HT) immunoreactivity below the level of the lesion and improved locomotor recovery. Our results with the 205C CD11d mAb treatment complement previous work using this anti-integrin treatment in a rat model of SCI.     

Pathological study on the relationship between C4d, CD59 and C5b-9 in acute renal allograft rejection

Abstract:  In order to evaluate the activation or inhibition of the later phases of classical complement cascade in renal allograft presenting with acute rejection, particularly with C4d deposition on the peritubular capillary (PTC), we observed the expression of CD59 and C5b-9 on the PTC. Subjective cases were divided into two groups, an acute rejection group, of 4 males and 6 females, and a normal donor group, of 5 males and 5 females. Renal biopsies were performed at the onset of acute rejection and at the transplant operation, before reperfusion. C4d deposition on PTC was found in three of 10 cases (30%) with biopsy proven acute rejection, whereas CD59 on PTC was positively expressed in all of the rejection cases. Although C5b-9 was not observed on PTC in the acute rejection group, it was intensively deposited on the tubular basement membrane (TBM) in five cases, including the three with positive C4d on PTC. In the normal donor group, CD59 on PTC was intensively observed, whereas C5b-9 was weakly expressed on TBM. CD59, a complement regulatory factor, works as an inhibitory factor against the formation of C5b-9, a membrane attack complex. From our data, we noted the dissociation between the depositions of C4d and C5b-9 on PTC. The substantially expressed CD59 on PTC may affect this dissociation between C4d and C5b-9 on PTC. The intensive deposition of C5b-9 on TBM in acute rejection cases may suggest an independent immunological injury attacking tubular cells.     

Prostaglandin E1 reduces compression trauma-induced spinal cord injury in rats mainly by inhibiting neutrophil activation

Prostaglandin E1 (PGE1), a potent vasodilator, was recently reported to inhibit both neutrophil activation and monocytic production of tumor necrosis factor-alpha (TNF-alpha) in vitro. We previously reported that TNF-alpha was critically involved in the development of motor disturbances by increasing the accumulation of neutrophils at the site of injury in rats subjected to compression trauma-induced spinal cord injury. Therefore, it is possible that PGE1 reduces motor disturbances by inhibiting neutrophil activation in rats subjected to spinal cord injury. We examined this possibility in a rat model of spinal cord injury (SCI). Motor disturbances induced by spinal cord compression were evaluated using the inclined plane test, and footprint analysis. Accumulation of neutrophils at the site of trauma was evaluated by measuring tissue myeloperoxydase (MPO) activity. Tissue levels of TNF-alpha were determined using an enzyme-linked immunosorbent assay. Motor disturbances induced by spinal cord compression were significantly attenuated in rats administered PGE1. A histological examination revealed that intramedullary hemorrhages, observed 24 h after trauma, were markedly reduced in animals administered PGE1. Increases in the tissue levels of TNF-alpha and MPO activity in the damaged segment of spinal cord were significantly inhibited in animals that had received PGE1. These observations suggested that PGE1 reduces motor disturbances by inhibiting neutrophil activation directly or indirectly through the inhibition of TNF-alpha production at the site of injury. These effects of PGE1 might at least partly contribute to therapeutic effect on SCI in rats.     

无颈椎骨折脱位的急性颈髓损伤

目的探讨无颈椎骨折脱位的急性颈髓损伤的特征和机制.方法对33例无颈椎骨折脱位的急性颈髓损伤病例进行回顾性研究,分析其神经学、X线和MRI检查结果.结果颈髓完全性损伤者8例,不完全性损伤者25例;21例患者有颈椎变性改变(椎间盘间隙狭窄伴有骨赘形成者15例,后纵韧带骨化者6例),3例C5颈椎管Pavlov率小于0.8;30例可见颈髓受压,25例表现为椎旁软组织损伤.结论无颈椎骨折脱位的急性颈髓损伤的重要诱因为颈椎变性改变和发育性颈椎管狭窄,致病原因主要为颈髓受压;MRI检查有利于查明脊髓损伤的部位和机制.     

Glomerular complement regulation is overwhelmed in passive Heymann nephritis

BACKGROUND: An injection of anti-Fx1A antibodies in rats leads to passive Heymann nephritis (PHN), a model of membranous nephropathy. Fx1A is a crude extract of renal cortex that contains megalin as a principal component. However, when rats are given anti-megalin antibodies, abnormal proteinuria does not occur. Because of the established complement dependence of PHN, we hypothesized that antibodies neutralizing complement regulatory proteins in the rat glomerulus also were required to induce PHN. Two likely targets are Crry and CD59, proteins abundant on the rat podocyte and contained within Fx1A that inhibit the C3 convertase and C5b-9 assembly, respectively. METHODS: Rats were injected with anti-megalin monoclonal antibodies, followed by anti-Crry and/or anti-CD59 F(ab')(2) antibodies five days later. In a second group of experiments, rats were injected with anti-Fx1A or anti-Fx1A immunodepleted of reactivity against Crry and/or CD59. RESULTS: In the setting of podocyte-associated anti-megalin monoclonal antibodies, simultaneous neutralization of Crry and CD59 function led to the development of significant proteinuria (11.0 +/- 2.1 mg/day, P < 0.001 vs. all other groups). In contrast, animals that had neither or only one of these complement regulators inhibited had normal urinary protein excretion (< or =6 mg/day). In animals given anti-Fx1A depleted of anti-Crry and/or anti-CD59, all groups developed typical PHN, characterized by heavy proteinuria and extensive glomerular deposition of C3 and C5b-9. CONCLUSION: Crry and CD59 play an important role in restraining complement-mediated injury following subepithelial immune complex deposition; however, in PHN, their regulatory capacity is overwhelmed.