雷帕霉素对急性肝功能衰竭大鼠Toll样受体-4表达的影响

目的 探讨雷帕霉素抑制Janus激酶/信号转导和转录激活子(JAK/STAT)通路对急性肝功能衰竭大鼠Toll样受体(TLR)-4基因表达的影响.方法采用腹腔注射D-氨基半乳糖(D-GalN)800 mg/kg和脂多糖(LPS)8 μg/只,建立急性肝功能衰竭大鼠模型,分别在注射D-GalN和LPS后2、6、12、24、48 h 5个时间点留取大鼠血及肝脏标本.SD大鼠分为对照组(n=6)、急性肝功能衰竭模型组(n=30)、STAT抑制剂雷帕霉素(RPM)干预组(n=30),在各不同时间点检测ALT、AST.ELISA法检测血清TNF-α、IL-6水平,RT-PCR法检测大鼠肝组织TLR-4 mRNA表达.数据行t检验.结果急性肝功能衰竭组大鼠在造模后2 h TNF-α、IL-6水平均显著升高,6 h达峰值,RPM可明显抑制TNF-α、IL-6水平.急性肝功能衰竭组大鼠6、12、24、48 h肝组织中TLR-4 mRNA分别为0.745±0.135、1.092±0.175、1.115±0.152和0.812±0.130,RPM干预后分别为0.545±0.118、0.798±0.124、0.857±0.109和0.595±0.152,各时间点两组比较,差异均有统计学意义(t值分别为2.726、3.349、3.382和2.567,均P＜0.05).TLR-4 mRNA表达与ALT、AST均呈正相关(r值分别为0.722、0.712,均P＜0.01).结论抑制JAK/STAT通路可明显下调急性肝功能衰竭大鼠肝组织TLR-4表达,JAK/STAT通路可能参与急性肝功能衰竭过程中TLR-4mRNA表达的调控.     

重组人脑利钠肽治疗老年慢性心衰患者急性加重期的临床疗效观察

目的 观察重组人脑利钠肽(rhBNP)治疗老年慢性心衰急性加重期的临床疗效,对心功能、血清B型脑利钠肽(BNP)和去甲肾上腺素(NE)水平的影响.方法 89例年龄≥65岁的慢性心衰急性加重期患者随机分为rhBNP治疗组(n=47)和硝普钠治疗组(n=42),观察两组患者治疗前后的临床疗效、心功能及血清BNP和NE水平的变化.结果 rhBNP组治疗后24 h临床显效率(51.06%)及总有效率(95.74%)均高于硝普钠组(分别为42.86%及83.33%,P<0.05);rhBNP组治疗后2 w射血分数(EF)值升高[(46.2±9.5)% vs (38.1±6.0)%,P<0.05];rhBNP组治疗后2 w血清BNP水平较硝普钠组下降(P<0.05);rhBNP组治疗后24 h血清BNP及NE水平均较基线值明显下降(P<0.01),且治疗后2 w较24 h有进一步降低(P<0.01);硝普钠组治疗后24 h血清 BNP及NE亦较基线值明显下降(P<0.01),治疗后2 w血清 BNP较24 h有进一步降低(P<0.01),但血清NE与治疗后24 h相比较差异不显著(P>0.05).结论 rhBNP能安全、有效地用于老年慢性心衰急性加重期的治疗.     

急性肝功能衰竭大鼠模型中程序性死亡-1及其配体的表达

目的 探讨程序性死亡-1(PD-1)/程序性死亡配体-1(PD-L1)在急性肝功能衰竭大鼠模型中的表达变化及其在肝脏急性炎性损伤中的作用.方法 SD大鼠分为2组:正常组6只,模型组30只,以D-氨基半乳糖(D-Gal)诱导急性肝功能衰竭大鼠模型.造模后分别在12、24、48、72和120 h取大鼠血及肝脏标本,采用RT-PCR法检测肝组织中PD-1 mRNA、PD-L1 mRNA的表达.计量资料组间比较用t检验,相关性检验用Pearson直线相关分析.结果 造模后12 h,大鼠血ALT、AST明显升高,分别为(217.3±33.7)U/L和(397.2±101.3)U/L,显著高于正常组的(30.5±3.1)U/L和(78.6±4.2)U/L,差异有统计学意义(t=-8.921,-6.121,均P＜0.01),至48 h达高峰.造模后12 h,模型组大鼠PD-1 mRNA表达(0.385±0.074)高于正常组(0.097±0.009),差异有统计学意义(t=-7.725,P＜0.01),48 h达高峰(0.927±0.132),72 h则明显下降.PD-L1mRNA在正常大鼠肝组织中表达很少,模型组PD-L1 mRNA水平逐渐升高,48 h达高峰(0.593±0.105)(t=-10.076,P＜0.01).造模后大鼠PD-1、PD-L1表达水平与血清ALT水平呈正相关(r=0.807,0.792,P＜0.01).结论 PD-1/PD-L1表达在急性肝功能衰竭大鼠肝脏炎性损伤中可能起重要作用.     

盐敏感性高血压患者昼夜血压变异性与尿钠排泄节律的关系

目的观察盐敏感性高血压患者24 h血压昼夜节律变化,探讨昼夜尿钠排泄改变与血压变异性的关系。方法选取住院的1²级原发性高血压患者58例,进行24 h动态血压监测,收集测量昼、夜尿钠排泄量。采用快速静脉输注生理盐水与呋塞米排钠缩容相结合的方法,测定盐敏感性。结果 58例受试者共检出盐敏感者25例(43.1%)。24 h动态血压监测结果显示,盐敏感(SS)组与盐不敏感(NSS)组白天血压比较,差异无统计学意义,但SS组收缩压夜间下降百分比(4.0%±2.0%比11.0%±3.0%)、舒张压夜间下降百分比(7.0%±4.0%比13.0%±4.0%)均显著小于NSS组(均为P<0.05)。SS组与NSS组24 h尿钠排泄量差异无统计学意义,但SS组夜间尿钠排泄量显著大于NSS组[(108.2±39.2)mmol比(70.6±35.0)mmol,P<0.01];SS组夜尿钠占全天百分比高于NSS组(48.0%±23.0%比35.0%±22.0%,P<0.05)。结论盐敏感性高血压患者夜间尿钠排泄量增加,致夜间血压代偿性升高,呈"非杓型"改变。     

雷帕霉素抑制JAK/STAT通路对急性肝损伤大鼠肝组织HMGB1表达的影响

目的：探讨雷帕霉素抑制JAK/STAT通路对急性肝损伤大鼠肝组织HMGB1表达的影响．方法：采用D-Galn/LPS复制急性肝损伤(ALI)模型．大鼠随机分为正常对照组(n=30)、ALI组(n=30)、STAT抑制剂雷帕霉素(RPM)处理组(n=30)．用Western blot方法测定肝组织HMGB41蛋白,全自动生化分析仪测定肝功能指标．结果：与正常对照组HMGB1表达水平(1．00±0．02)相比,ALI组24．72 h HMGB1表达显著升高(3．12±0．06,3．9±0．08,2．83±0．04,t值分别为16．01,3．86,10．46,均P＜0．01),血清丙氨酸转氨酶(ALT)6和24 h有两个峰值,且24 h峰值高于6 h．与ALI组相比,RPM预处理组24-72h HMGB1蛋白表达均显著抑制(1．67±0．05 vs 3．12±0．06：1．93±0．06 vs 3．9±0．08：1．47±0．04 vs 2．83±0．04：t值分别为20．11,41．90,26．02,均P＜0．01),ALT在24,48,72 h也均有不同程度下降(P＜0．01)．ALT与HMGB1呈正相关(r=0．741,P＜0．01)．结论：抑制JAK/STAT可明显下调肝组织中HMGB1蛋白表达,并有助于减轻D-Galn/LPS所致的急性肝损伤．     

肝组织清道夫受体A在急性重症胆管炎时的表达与内毒素性肝损伤的关系

目的: 研究急性重症型胆管炎(ACST)时大鼠内毒素性肝损伤与肝组织中清道夫受体A(SR-A)表达水平的关系.方法: Wistar大鼠随机分为2组, 第1组(急性胆道感染组, AOC组), 胆总管予以结扎并注入大肠杆菌O111B4建立ACST动物模型, 第2组(胆总管结扎组, BDL组), 结扎胆总管并注射等量生理盐水. 于术后0、4、8、16、24 h分别采用Western blot和RT-PCR检测肝组织中SR-A蛋白和基因表达水平; 以鲎试验和ELISA测定血浆内毒素和白介素-6(IL-6); 光镜观察肝组织病理变化并测定血浆ALT、TB含量.结果: 在ACST时随着病程的延长、血浆内毒素浓度逐渐升高(0-24 h: 0.058±0.009, 0.207±0.024, 0.433±0.049, 0.645±0.077, 0.784±0.097, P<0.01), 血浆IL-6、ALT和TB含量明显增加(均P<0.01), 肝功能减损, 同时肝细胞变性、坏死等病理改变逐渐加重, 而AOC组SR-A在术后4 h, 表达已开始下降( P<0.01), 随着病程延长其表达逐渐下降, 至24 h与BDL比较有明显显著性差异(蛋白: 0.156±0.014 vs0.809±0.107, P<0.01; mRNA: 0.138±0.019 vs0.578±0.068, P<0.01).结论: ACST时, 内毒素性肝损伤与肝组织SR-A表达水平的进行性下调有关. 随着枯否细胞清除内毒素的防御能力下降, 肝组织内毒素性损伤进行性加重.     

趋化因子Fractalkine在急性肝功能衰竭大鼠模型中的变化及意义

目的 探讨不规则趋化因子Fraetalkine(FKN,CX3CLl)在急性肝功能衰竭大鼠模型中的变化及其在肝脏炎性损伤中的作用.方法 SD大鼠分为健康对照组6只,模型组36只.D氨基半乳糖(D-Gal)诱导大鼠急性肝功能衰竭模型,造模后分别在12、24、48、72、120和168 h等6个时间点取大鼠血及肝脏标本,RT-PCR法检测肝组织中FKN mRNA、核因子(NF)-kB mRNA的变化.计量资料组间比较用t检验,相关性检验用Pearson直线相关分析.结果 造模后12 h,大鼠血ALT、AST值明显升高,分别为(208.3±43.5)U/L和(375.25:117.3)U/L,显著高于正常组的(31.8±2.9)U/L和(90.8±3.1)U/L,差异有统计学意义(t值分别为-9.912和-5.935,P＜0.01),72 h达高峰.造模后12 h,FKN mRNA为0.086±0.009,高于正常组的0.044±0.009,差异有统计学意义(t=-7.999,P＜0.01),72 h达高峰,为0.333±0.033,120 h则明显下降.NF-kB在正常大鼠肝组织中有少量表达,模型组随着时间推移,NF-kB水平逐渐升高,72 h达高峰,为0.583±0.101(t=-12.607,P＜0.01).FKN与NF-kB呈正相关(r=0.760,P＜0.01).结论 FKN在急性肝功能衰竭大鼠中的表达是肝损伤的重要因素,有可能为急性肝功能衰竭的治疗提供一个新的切入点.     

微波消融与腹腔镜肝切除术对肝血管瘤患者VAS及肝功能的影响

目的探讨微波消融与腹腔镜肝切除术对肝血管瘤患者视觉模拟评分(visual analogue scale,VAS)及肝功能的影响.方法选择2014-06/2016-12于河南省人民医院确诊肝血管瘤并选择手术治疗的患者79例,按照随机数字表法分为研究组(n=41例)及对照组(n=38例),研究组给予微波消融术进行治疗,对照组给予腹腔镜下部分肝切除术,然后记录两组患者手术用时、术中出血量、术后不良反应、住院总时间及术后12、24、48 h的VA S得分情况并进行对比,分别于术后1 d及3 d抽静脉血检查患者肝功能[谷丙转氨酶(alanine transaminase,ALT)及谷草转氨酶(aspartate transaminase,AST)]相关指标并进行对比.结果研究组患者手术时间低于对照组(38.63 min±11.74min vs 187.21 min±78.85 min,术中出血量低于术中出血量20.52 mL±7.45 mL vs 329.72 mL±104.63mL,P0.01).两组患者住院时间比较没有明显差异.研究组术后不良反应发生率(3%)明显低于对照组(36.8%)(P0.01).研究组患者术后12、24及48 h时的VAS得分均明显低于对照组(P0.01).研究组术后1 d的ALT及AST值明显高于对照组(P0.05).两组患者术后3 d的ALT及AST值没有明显差异.结论微波消融术治疗肝血管瘤患者效果显著,且在缩短手术时间、降低术中出血量、减少术后VAS评分的同时,还能够有效避免患者肝损伤,且安全性较好.     

N-乙酰半胱氨酸对重症急性胰腺炎大鼠肝损伤的保护作用

目的:探讨N-乙酰半胱氨酸(N-acetylcysteine,NAC)对重症急性胰腺炎(severe acute pan-creatitis,SAP)大鼠肝损伤的保护作用及作用机制.方法:Wistar大鼠42只随机分为3组,SAP组(SAP,n=18),采用逆行十二指肠胰胆管注射50 g/L牛黄胆酸钠溶液制备SAP模型;SAP+NAC组(SAP+NAC,n=18),建模前2 h给予NAC 300 mg/kg体质量预处理;假手术组(SO,n=6).建模成功后3、6和12 h,分别取下腔静脉血液、胰腺和肝脏组织.光镜下观察胰腺和肝脏组织病理改变,全自动生化分析仪检测各时段血液ALT和AST水平,逆转录-聚合酶链反应(RT-PCR)检测肝脏组织中TNF-αmRNA表达,SP免疫组化法检测肝脏组织中NF-κB活化.结果:SO组血液ALT、AST以及肝胰组织病理无显著性变化.SAP组各时间点肝胰病理改变较SO组严重.术后3、6和12 h时间点ALT及AST均较SO组显著升高(186.67±27.28,321.17±56.14,492.50±69.77 vs 36.83±7.02;255.50±44.15,343.17±43.70,425.33±58.37 vs 41.67±5.35,P<0.05或0.01);TNF-αmRNA表达均显著高于SO组(0.37±0.03,0.77±0.04,0.54±0.04 vs 0.24±0.03,P<0.05或0.01):NF-κB活性术后3、6 h均显著高于SO组(51.95±4.76.24.67±4.93 vs 9.33±2.05,P<0.05或0.01),12 h与SO组相比差异无显著性意义.SAP+NAC组各时间点肝胰组织病理改变均较SAP组减轻,术后3-12 h血液ALT及AST水平(143.67±16.62,203.33±25.41,301.17±26.82;136.33±26.27,221.50±38.31,310.50±38.17)均显著低于SAP组(P<0.05或0.01);各时间点肝脏TNF-αmRNA表达(0.25±0.03,0.50±0.05,0.43±0.03)显著低于SAP组(P<0.05或0.01);术后3-6 h NF-κB活性(37.60±6.37,12.88±2.66)均较SAP组显著降低(P<0.05).结论:NF-κB活化与TNF-αmRNA表达上调参与了SAP大鼠肝损伤过程,NAC 300 mg/kg预处理能够有效减轻SAP大鼠肝损伤,其作用机制可能与抑制NF-κB活化进而下调炎性细胞因子TNF-αmRNA表达水平相关.     

单剂量二甲双胍改善急性糖负荷对高血压患者血管内皮功能的损伤

目的 探讨单剂量二甲双胍(MF)对原发性高血压患者在急性糖负荷后的内皮依赖性血管舒张功能、血清抗氧化物质及游离脂肪酸的影响.方法 入选未经降压治疗的原发性高血压(EH)患者39例,随机分为高血压对照组(EH组,未服用降压药,n=26)和二甲双胍组(MF组,服用单剂量MF,0.5 g/d,n=13);另选择同期健康体检者设为正常对照组(n=15).入选者禁食12 h后,口服葡萄糖耐量试验(OGTT).以高分辨率血管彩超测定糖负荷0、1、2、3 h后肱动脉血流介导的内皮依赖性血管舒张功能(FMD).检测血清中超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)、抗超氧阴离子自由基(AntiO2-)和游离脂肪酸(FFA)的水平.结果 急性糖负荷1 h后,EH组和正常对照组的FMD显著下降EEH组(9.5±3.3)%比负荷前(13.6±5.0)%,P<0.05;正常对照组(14.4±5.9)%比负荷前(17.4±5.7)%,P<0.05],MF抑制糖负荷对FMD的影响EMF组1 h:(14.5±6.2)%比负荷前:(14.5±6.0)%,P>0.05].急性糖负荷后1 h,EH组的SOD、T-AOC及AntiO2-浓度较空腹时显著下降,MF抑制了急性糖负荷引起的SOD和T-AOC水平下降(P<0.05),Anti O2-水平甚至比负荷前明显升高[(256.8±72.2)U/L比负荷前(224.8±67.8)U/L,P<0.05],且FFA浓度比糖负荷前明显下降[(108.1±53.1)μmol/L比负荷前(236.6±80.5)μmol/L,P<0.05].结论 单一剂量的MF能改善急性糖负荷对高血压患者血管内皮功能的一过性损害,该作用可能与恢复抗氧化能力、降低游离脂肪酸水平有关.     

Severe acute pancreatitis in acute hepatitis E.

We report an 18-year-old boy with severe acute pancreatitis developing during acute hepatitis E and complicated by sepsis and acute renal failure. The patient recovered on supportive management.     

Myocarditis associated with acute nasopharyngitis and acute tonsillitis

Thirty-five instances of fatal myocarditis atributable to acute nasopharyngeal and tonsillar infections have been reported. The available evidence indicates that these are samples of a not uncommon type of cardiac disease which fortunately has a relatively good prognosis. Further investigation should be carried on to establish fully the etiological agent and the pathogenesis of the lesion. Although the pathologic observations indicated that all patients died of cardiac failure, heart disease was suspected clinically in only three, and in fifteen patients death was unexpected. Significant clinical observations which would seem to be of importance in the recognition of the process were: disproportion of the temperature and pulse rate, hypotension, thready or feeble pulse, and substernal oppression. Cyanosis, dyspnea, and orthopnea occurred frequently.Autopsy findings included significant enlargement of the heart in many cases. The microscopic changes, similar in both nasopharyngeal and tonsillar infections, have been classified in three overlapping groups. In all of these the inflammatory process was observed to be patchy, frequently showing considerable variation in intensity from one area to another and having no predilection for a particular portion of the myocardium. Significant (moderate or marked) degrees of muscle degeneration observed in the diffuse type of myocardial lesion were not present in the interstitial form. The cellular reaction, which was characteristically more intense than that observed in diphtheritic myocarditis, was predominantly mononuclear, but significant numbers of polymorphonuclear leucocytes accumulated at sites of more severe inflammation.Although the figures are too small to justify conclusions, there appears to be significant correlation between the clinical occurrence of hypotension and the estimated severity of the myocarditis, since it was a feature in every severe case in which the blood pressure was recorded. The only available electrocardiograms (four), abnormal in every case, were from patients whose hearts showed muscle degeneration of moderate or marked degree. Anginal pains were related to the presence of hypotension. Fibrosis of the heart muscle was related both to the muscle degeneration and to duration of illness.In therapy, attention is called to the danger involved in the administration of intravenous fluids.     

Fatal idiopathic acute eosinophilic pneumonia with acute lung injury

A fatal case of idiopathic eosinophilic pneumonia with acute lung injury is described. The patient required treatment with mechanical ventilation and intravenous corticosteroids, however, she died on the third hospital day. At autopsy, both exudative and proliferative phases of diffuse alveolar damage were observed bilaterally. Marked eosinophilic infiltrate was noted in the alveolar wall and within the alveolar cavities with occasional abscess-like features. To our knowledge, this is the first report of fatal acute eosinophilic pneumonia, and provides important information for the management of this condition.     

Philadelphia chromosome-positive acute lymphoblastic leukemia preceded by acute pleuropericarditis

A 69-year-old woman was admitted with sudden chest pain and high fever. Electrocardiography showed negative T waves in the precordial leads. Subsequently, pleural and pericardial effusion developed, but the symptoms and signs subsided without specific therapy. On day 31, fever, left shoulder pain and pleural effusion reappeared. 67Ga scintigraphy showed abnormal uptake in the chest and left shoulder. Blasts were detected in the peripheral blood on day 44, and in the pleural effusion and bone marrow on day 45. The blasts were positive for Philadelphia chromosome, CD10, CD19, CD33, CD34 and IgH-chain rearrangement and negative for myeloperoxidase. The clinical picture of the preceding pleuropericarditis was that of viral or idiopathic origin, but its relationship with acute lymphoblastic leukemia was unclear. Inflammatory chemokines in the pleural space may have induced invasion of the leukemic cells.