丙戊酸钠对脂多糖诱导大鼠急性肺损伤的保护作用

目的 研究丙戊酸钠(valproic acid,VPA)对脂多糖(lipopolysaccharide,LPS)诱导的大鼠急性肺损伤的影响.方法 实验地点在武汉协和医院中心实验室,通过股静脉注射LPS复制大鼠急性肺损伤模型,观察光镜下肺组织病理学改变、血清炎性因子和肺部炎性反应判定模型是否成功.依据干预药物的不同确定实验分组:股静脉给予5mL/kg生理盐水为对照组(NS组),股静脉给予LPS 10 mg/kg为模型组(LPS组),模型成功后股静脉给予VPA 300mg/kg治疗为治疗组(LPS+VPA组).注射LPS或NS后6 h处死动物,血气分析观察动脉血氧分压(PaO2)、肺泡气-动脉血氧分压差(A-aDO2)、乳酸(Lac),检测肺组织干湿重比(W/D),髓过氧化物酶(MPO)活性,肺泡灌洗液(BALF)中白蛋白质量浓度,用ELISA法检测6 h血清中TNF-α和IL-1β的含量,HE染色光镜下观察肺组织病理学变化.计量资料以均数±标准差(-x±s)表示,应用SPSS 13.0统计软件行单因素方差分析.结果 LPS组PaO2(mmHg)(81.50±3.24)较NS组(106.40±4.50)降低,A-aDO2(mmHg),Lac[(19.70±2.21),(3.63±0.22)]较NS组[(6.30±1.70),(1.21±0.19)]升高,W/D,MPO活性(μ/g),BALF中白蛋白质量浓度(pg/mL)分别为[(6.52±0.30),(7.25±0.49),(2.940±0.047)]较NS组[(4.38±0.17),(1.76±0.31),(0.099±0.077)]升高,血清中TNF-α和IL-1β的质量浓度(pg/ml)分别为(3325±284),(1950±222)较NS组(90±12),(50±11)显著升高,差异具有统计学意义(P＜0.05),LPS组肺组织出现病理学改变;与LPS组比较,LPS+VPA组上述指标除PaO2(mmHg)(94.50±4.38)上升外,其余指标均降至[(13.50±4.77),(2.13±1.02),(5.33±0.12),(4.38±0.42),(1.260±0.039),(2410±320),(1220±162)],差异具有统计学意义(P＜0.05),LPS+VPA组肺组织病理学改变明显减轻.结论 丙戊酸钠对脂多糖诱导的大鼠急性肺损伤有一定保护作用.

Abstract：

Objective To investigate the effects of valproic acid (VPA) on acute lung injury induced by Lipopolysaccharide in rats. Method The rat model of acute lung injury was made by intravenous injection of lipopolysaccharide (LPS). The pathological changes of lung were observed under light microscope and inflammatory cytokines in serum detected by using ELISA to judge whether the model was successfully done or not. All rats were divided into three groups as per the different intervention agents employed. Rats in control group were treated with intravenous injection of NS in dose of 5 ml/kg, rats in LPS group were exposed to LPS with dosage of 10 mg/kg and model rats in LPS + VPA group were treated with VPA in dose of 300 mg/kg. The rats were sacrificed 6 h after LPS or NS administration. The blood PaO2 ,A-aDO2 and blood lactic acid (Lac) were measured, the lungs were removed for observing the histopathological changes and determination of wet/dry lung weight (W/D) ratio and myeloperoxidase (MPO) activity as well as albumin concentration in broncho-alveolar lavage fluid (BALF) . Seurm was collected to determine the concentrations of tumor necrosis factor-a (TNF-α) and interleukin-1β( IL-1 β) by using LISA 6 h later. All data were presented in ((x)±s). One-way ANOVA was used for comparing differences between groups. Results Compared with acute lung injury group, the blood PaO2 (94. 50 ± 4.38 ) in rats of LPS + VPA group was higher, whereas A-aDO2 ( 13.50 ± 4.77 ) and blood lac( 2.13 ± 1. 02 ) in LPS + VPA group were lower. VPA significantly lowered W/D (5.33 ±0. 12) ratio and MPO activity (4.38 ±0. 42) in the lung. Albumin concentration ( 1. 260 ± 0. 039 ) in BALF, and the levels of TN F-α( 2 410 ±320 )and IL-1β( 1 220 ± 162 )in serum were lower in LPS + VPA group. The histological changes of lung injury were lessened by VPA. Conclusions Valproic acid has protective effects against lipopolysaccharide-induced acute lung injury in rats.     

参附注射液对内毒素所致肺损伤的保护作用

目的探讨参附注射液（SF）对内毒素（ET）所致肺损伤的保护作用机制。方法采用尾静脉注射内毒素致急性肺损伤模型，并于腹腔注射参附注射液进行干预，另设生理盐水（NS）对照组。观察肺组织病理学检查及评分、肺湿干质量比（W／D）、肺组织核因子-κB（NF—κB）的表达、血中肿瘤坏死因子-α（TNF—α）含量等的变化。结果ET组肺W／D、肺NF-κB表达、血TNF-α含量、肺组织病理学检查及评分较NS组显著升高，动脉血氧分压（PaO2）显著下降；而ET＋SF组与ET组比较肺W／D、肺NF—κB表达、血TNF—α含量、肺组织病理学检查及评分显著下降，PaO2显著上升。结论参附注射液可能通过减少肺组织NF—κB的激活，进而减少NF—κB的产生而起到肺保护作用。     

乌司他丁对大鼠急性肺损伤保护作用的实验研究

乌司他丁作为一个具有广泛抑制各种细胞因子产生的药物,在急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)方面的治疗作用日益受到重视,本研究拟探讨其保护作用机制,报告如下.     

川芎嗪对急性肺损伤的保护作用

目的：研究川芎嗪对急性肺损伤的保护作用。方法：家兔24只，随机分为3组。A组为假手术组，只进行相应的手术操作；B组和C组制作失血性休克模型，造成急性肺损伤，然后在20min内复苏，C组复苏时应用用芎嗪。测定动脉血浆中肿瘤坏死因子-α（TNF-α）含量、支气管肺泡灌洗液（BALF）中巨噬细胞（PAM）和中性粒细胞（PMN）总数．BALF中蛋白含量和肺组织中超氧化物歧化酶（SOD）含量；计算肺组织含水率；光镜下观察肺组织形态学改变。结果：与A组比较，复苏后B、C组TNF-α含量、BALF中的蛋白含量和PMN总数、肺组织含水率明显升高，SOD含量明显降低。但C组上述指标的变化程度均低于B组。光镜下见B组肺组织间质水肿、细胞浸润明显，与之相比C组肺组织以上改变明显减轻。结论：川芎嗪时急性肺损伤具有保护作用。     

胰岛素在急性呼吸窘迫综合症中的临床应用

目的:观察胰岛素在急性呼吸窘迫综合症中的抗炎作用,并探讨其机制.方法:将78名急性呼吸窘迫综合症的患者随机分成胰岛素治疗组(A组)和对照组(B组),对A组患者给予呼吸机辅助等常规治疗的同时持续性静脉输注胰岛素.使其血糖维持在4.0～8.0mmol/L;对B组患者常规使用呼吸机辅助及抗生素治疗,分别于入院当时(0 h)、入院后24 h、48 h、72 h留取外周静脉血标本,用放射免疫法测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-4(IL-4)浓度.结果:A组和B组TNF-α、IL-6浓度逐渐下降,IL-4浓度逐渐上升;与对照组比较有统计学意义.结论:胰岛素可降低促炎细胞因子浓度,同时升高抗炎细胞因子浓度,从而恢复细胞因子稳态.     

联合应用纳洛酮与甲基强的松龙对大鼠急性肺损伤的保护作用

目的　探讨联合应用甲基强的松龙、纳洛酮对内毒素所致急性肺损伤大鼠的防治作用及可能机制。方法　建立大鼠内毒素吸入性ALI模型 (LPS ,3mg/kg气管内注射 ) ,85只大鼠随机分为生理盐水对照组、内毒素损伤组、甲基强的松龙组 (内毒素 甲基强的松龙 )、纳洛酮组 (内毒素 纳洛酮 )、联合用药组 (内毒素 甲基强的松龙 纳洛酮 )。采用放射免疫方法检测大鼠血清TNF -α、IL - 8水平 ,并观察动脉血气分析及肺组织病理变化。结果　内毒素损伤组较生理盐水组TNF -α、IL - 8水平明显增高 ,动脉血氧分压明显降低 ,肺组织可见肿胀、淤血、炎细胞浸润。联合用药组各项指标较内毒素损伤组均轻。结论　联合应用甲基强的松龙和纳洛酮可降低气管内注入内毒素致大鼠ALI血清TNF -α、IL - 8升高水平 ,减轻肺损伤病理改变程度 ,对大鼠ALI有防治作用     

丹参酮对大鼠急性肺损伤保护作用的实验研究

目的探讨丹参酮对急性肺损伤(ALI)大鼠肺组织的保护作用及其可能机制。方法 45只健康雄性Wistar大鼠随机分为对照组(NS组)、急性肺损伤组(LPS组)、丹参酮IIA磺酸钠干预组(STS组),LPS组和STS组通过股静脉注射LPS(5 mg/kg)建立急性肺损伤模型。STS组在注射LPS前30 min静脉给药10mg/kg,NS组和LPS组给予等量NS。分别在6 h、12 h、24 h三个时间点活杀大鼠,检测血气分析、肺组织湿/干重比(W/D)、HE染色、采用酶联免疫吸附分析法检测各时相点大鼠血浆中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)浓度。结果与LPS组相比,STS组急性肺损伤的程度明显减轻,PaO2显著改善(P<0.05),肺W/D比值降低(P<0.05),HE染色显示肺组织损伤减轻。STS组血浆TNF-α、IL-6浓度较LPS组相应时相点显著下降,而IL-10浓度明显升高,高峰提前(P<0.05)。结论丹参酮对AL I大鼠肺组织具有一定的保护作用,其机制可能是抑制了TNF-α、IL-6的释放,增加IL-10的释放,使促炎-抗炎平衡,减轻肺部及全身的炎性反应。     

清除血液中内毒素、肿瘤坏死因子和白细胞介素-1对实验性内毒素休克时肺损伤的保护作用

目的：了解内毒素（ＬＰＳ）、肿瘤坏死因子（ＴＮＦ）和白细胞介素１（ＩＬ１）对实验性内毒素休克时肺损伤的保护作用。方法：实验分３组：Ⅰ组为假灌流组，Ⅱ组、Ⅲ组大鼠在内毒素休克早期开始分别给予活性炭（Ⅱ组）、大孔树脂ＡｍｂｅｒｌｉｔｅＸＡＤ７（Ⅲ组）血液灌流，结果与Ⅰ组作比较。结果：Ⅱ组ＬＰＳ、ＩＬ１水平明显降低，而Ⅲ组ＴＮＦ水平明显降低。Ⅱ组、Ⅲ组外周血白细胞数分别为（４．０±０．４）×１０９／Ｌ和（３．９±０．４）×１０９／Ｌ，均明显高于Ⅰ组〔（３．１±０．２）×１０９／Ｌ〕，Ｐ均＜０．０１；支气管肺泡灌洗液（ＢＡＬＦ）中的白细胞数〔（８．５±０．１）×１０９／Ｌ，（８．９±０．１）×１０９／Ｌ〕、肺系数（０．６４±０．０６，０．６６±０．０６）以及肺组织浸润的中性分叶核粒细胞数（２９．６±７．９／ＨＰ，３４．５±４．１／ＨＰ）均明显低于Ⅰ组〔（１２．３±１．８）×１０９／Ｌ，０．７５±０．０７，４８．６±６．６／ＨＰ〕，Ｐ均＜０．０１或＜０．０５。Ⅱ组、Ⅲ组的肺组织学改变亦较Ⅰ组明显减轻。结论：清除血液中致病介质可能对内毒素休克时的肺损伤产生保护作用。     

降钙素基因相关肽对内毒素急性肺损伤的保护作用

目的:探讨降钙素基因相关肽(CGRP),对内毒素急性肺损伤(ALI)的保护作用.方法:应用内毒素(LPS,6 mg/kg,iv)复制大鼠ALI模型.选用SD大鼠24只,随机分成盐水对照组(NS,n=8)、ALI模型组(LPS,n=8)、CGRP干预组(n=8).CGRP干预组按2μg/kg经腹腔注入CGRP,30 min后再经颈静脉注入LPS;LPS组以生理盐水代替CGRP;NS组中,CGRP和LPS均以等量生理盐水代替.各组大鼠均于注射LPS或生理盐水6 h后测定动脉血氧分压(PaO2)、血清肿瘤坏死因子(TNF-α)及白介素-8(IL-8)含量,随后处死动物,观察肺病理改变,测定肺湿/干重比(W/D)及肺组织匀浆髓过氧化物酶(MPO)浓度.结果:注射LPS 6 h后,W/D、肺组织匀浆MPO、血清TNF-α、IL-8含量较对照组均有显著升高(P＜0.01),PaO2显著降低;而预先给予CGRP(2μg/kg)干预可显著缓解上述变化,PaO2改善,MPO含量较ALI模型组降低(P＜0.05),肺组织病理改变明显减轻.结论:小剂量CGRP能改善大鼠ALI时气体交换功能,抑制炎症介质的释放,对内毒素诱导的ALI有保护作用.     

胰岛素在危重患者中的抗炎作用

目的观察胰岛素对危重患者TNF—α、IL-6和IL-4的影响，探讨其抗炎作用机制。方法将36例危重患者随机分为三组。即高胰岛素组（Ⅰ组，n=12），常规胰岛素组（Ⅱ组，n=12）和对照组（Ⅲ组，n=12）。Ⅰ组和Ⅱ组胰岛素为持续静脉泵入，Ⅰ组剂量为8U／h，Ⅱ组剂量为4U／h，Ⅲ组仅在血糖高于8．0mmol／L时，皮下注射胰岛素。三组患者血糖水平均维持在4．0～8．0mmol／L之间。分别于0、24、48和72h留取外周静脉血标本，用放射免疫法测定血清TNF—α、IL-6和IL-4浓度。结果高胰岛素组和常规胰岛素组TNF—α、IL-6浓度逐渐下降，IL-4浓度逐渐上升；与对照组比较。均有统计学意义；高胰岛素组与常规胰岛素组比较。TNF--α、IL-6浓度降低和IL-4浓度升高亦有统计学意义。结论胰岛素可降低促炎细胞因子浓度，同时升高抗炎细胞因子浓度，从而恢复细胞因子稳态，且此作用具有剂量依赖性。     

LPS诱导急性肺损伤大鼠肺组织甲状腺转录因子-1表达变化

目的探讨内毒素（LPS）诱导的急性肺损伤（ALI）大鼠肺组织甲状腺转录因子-1（TTF-1）、肺表面活性物质相关蛋白-A（SP—A）表达的变化。方法采用免疫组化和RT—PCR检测各组肺组织TTF-1、SP—A表达。结果ALI后12、24h，肺组织中TIF-1、SP—A表达水平明显降低，且TTF-1蛋白变化与SP—A mRNA变化呈显著正相关。结论ALI大鼠肺组织TIF-1表达明显降低可能与ALI发生、发展有关。     

加味金芙膏外敷防治甘露醇所致兔耳缘静脉炎的实验研究

目的：探讨加味金芙膏外敷对甘露醇所致静脉炎的防治效果。方法将家兔13只随机分为A组6只,B组7只。用20％甘露醇2.5 ml／kg静脉输注制作动物模型。左右耳自身对照,观察加味金芙膏外敷对甘露醇所致静脉炎发生的预防措施作用,以及加味金芙膏外敷对静脉炎的治疗作用。实验结果采用INS标准进行评分,实验结束后取耳进行组织病理学观察。结果预先给予加味金芙膏能明显降低INS分值,改善甘露醇注射所致的静脉炎症性病理改变,与模型组比较差异显著（ P＜0.05）。对于已经发生的静脉炎,加味金芙膏也有明显的治疗作用（ P＜0.01）。结论外敷加味金芙膏能可有效防治甘露醇所致静脉炎。     

血管生成素-1在光气急性肺损伤中的作用

目的 观察大鼠光气染毒后Ang-1,NF-κB水平变化,探讨Ang-1在光气所致大鼠急性肺损伤中的作用机制.方法 (1)大鼠随机(随机数字法)分为光气组和空气组.(2)大鼠分为光气组、PDTC组和空气组.(3)大鼠气体和药物处理后常规饲养到预定时刻取肺汁算湿/干质量比值,BALF白细胞数、总蛋白和血清Ang-1水平.测动脉血气,检测肺组织Ang-1和NF-κB水平.结果 (1)光气染毒后48 h内血清Ang-1随着时间延长有降低趋势.(2)干预实验中,①光气组肺损伤指标与空气组比较均增高(P＜0.05);②光气组血清Ang-1、动脉血氧分压与空气组比较均降低(P＜0.05);③光气组肺损伤程度与干预组比较均增高(P＜0.05);④光气组血清Ang-1、动脉血氧分压与PDTC组比较均降低(P＜0.05).⑤肺蛋白印迹与免疫组化结果一致,结果显示:空气组Ang-1表达正常;光气组Ang-1表达明显减少;PDTC组与光气组相比Ang-1表达增高,与空气组相比表达减少.空气组NF-κB表达正常;光气组NF-κB表达明最增高;PDTC组与光气组相比NF-κB表达降低,与空气组相比表达增高.结论 (1)光气染毒后48 h内随着时间延长,血清Ang-1水平降低.(2) Ang-1通过NF-κB信号传导通路,减轻炎症因子介导的炎症反应,减轻肺脏内皮通透性,减轻急性肺脏损伤.     

The ultra-early protective effect of ulinastatin on rabbit acute lung injury induced by paraquat

Objective

To study ultra-early pathophysiological changes of rabbit acute lung injury (ALI) caused by paraquat (PQ) and discuss the ultra-early protective effect of ulinastatin on rabbit ALI due to PQ.

Methods

30 New Zealand white rabbits were randomly divided into a control group, a paraquat group and an ulinastatin intervention group with 10 rabbits in each group. For paraquat group and intervention group a single dose of paraquat (35mg/kg) was injected intraperitoneally to establish rabbit models of ALI. The control group was injected an equal volume of saline. The intervention group was treated with 100Ku/kg ulinastatin immediately after the establishment of the ALI model. The respective experimental groups underwent 320-slice CT perfusion scan of pleural at 2h, 4h and 6h time point after modeling to get CTP (CT Perfusion) images and related parameters. 2mL blood was collected in the marginal ear vein to determine the mass concentration of the vascular endothelial growth factor (VEGF). The animals were killed by air embolism after 6h and lung tissue was taken for pathology observation.

Results

The reginal blood flow (rBF) and reginal blood volume (rBV) of paraquat group at 2,4,6 h time point were significantly (P <0.05) lower than those of control group. The intervention group rBF and rBV at 2, 4 and 6 h time points were significantly higher (P <0.05) compared to paraquat group. The permeability surface (rPS) and VEGF mass concentration of paraquat group at 2,4,6 h time point were significantly higher than the control group (P <0.05), and the intervention group rPS and VEGF mass concentrations at 2,4,6h time point were significantly lower (P <0.05) than those of paraquat group. Pathological detection indicators of paraquat group (congestive capillary percentage, the number of red blood cells outside of capillaries, percentage of capillaries with basement membrane damage) were significantly higher (P <0.05) at 6h time point compared with the control group, while significantly lower (P <0.05) in intervention group than in paraquat groups. Pathological observation under light microscope showed in paraquat group obvious inflammatory cell infiltration, alveolar epithelial cell hyperplasia, widened alveolar septum, visible focal hemorrhage, visible acute and chronic inflammatory cell infiltration in bronchioles cavity; under electron microscopy alveolar epithelial cell degeneration and necrosis, vascular welling of the endothelial cells, basement membrane rupture, a lot of exudates in alveolar space. In the intervention group, the above the symptoms were mitigated.

Conclusion

In the ultra-early stage of rabbit ALI induced by PQ, pulmonary vascular endothelial cell is damaged and serum VEGF mass concentration and pulmonary vascular permeability increase. Early ulinastatin intervention can reduce serum VEGF level and PQ-induced vascular permeability amplitude, indicating that ulinastatin has a protective effect on pulmonary vascular endothelial cells.

     

The ultra-early protective effect of ulinastatin on rabbit acute lung injury induced by paraquat

Background

Identification of delirium in emergency departments (ED) is often underestimated; within EDs, studies on delirium assessment and relation with patient outcome in Intermediate Care Units (IMCU) appear missing in European hospital settings. Here we aimed to determine delirium prevalence in an EDIMCU (Hospital de Braga, Braga, Portugal) and assessed routine biochemical parameters that might be delirium indicators.

Methods

The study was prospective and observational. Sedation level was assessed via the Richmond Agitation-Sedation Scale and delirium status by the Confusion Assessment Method for the ICU. Information collected included age and gender, admission type, Charlson Comorbidity Index combined condition score (Charlson score), systemic inflammatory response syndrome criteria (SIRS), biochemical parameters (blood concentration of urea nitrogen, creatinine, hemoglobin, sodium and potassium, arterial blood gases, and other parameters as needed depending on clinical diagnosis) and EDIMCU length of stay (LOS). Statistical analyses were performed as appropriate to determine if baseline features differed between the ‘Delirium’ and ‘No Delirium’ groups. Multivariate logistic regression was performed to assess the effect of delirium on the 1-month outcome.

Results

Inclusion and exclusion criteria were met in 283 patients; 238 were evaluated at 1-month for outcome follow-up after EDIMCU discharge (“good” recovery without complications requiring hospitalization or institutionalization; “poor” institutionalization in permanent care-units/assisted-living or death). Delirium was diagnosed in 20.1% patients and was significantly associated with longer EDIMCU LOS. At admission, Delirium patients were significantly older and had significantly higher blood urea, creatinine and osmolarity levels and significantly lower hemoglobin levels, when compared with No Delirium patients. Delirium was an independent predictor of increased EDIMCU LOS (odds ratio 3.65, 95% CI 1.97-6.75) and poor outcome at 1-month after discharge (odds ratio 3.51, CI 1.84-6.70), adjusted for age, gender, admission type, presence of SIRS criteria, Charlson score and osmolarity at admission.

Conclusions

In an EDIMCU setting, delirium was associated with longer LOS and poor outcome at1-month post-discharge. Altogether, findings support the need for delirium screening and management in emergency settings.     

运动对高脂喂养大鼠胰岛素抵抗的治疗作用

目的 观察运动对高脂饮食喂养大鼠胰岛素抵抗(IR)的影响,并初步探讨其机制.方法 将30只雄性Wistar大鼠分为对照组及高脂组,分别给予基础饲料和高脂饲料喂养;高脂组大鼠经喂养18周后制成IR模型,并进一步细分为静息组和运动组,继续给予高脂饲料喂养,运动组同时进行游泳训练,共持续6周.于实验进行24周后处死各组大鼠,检测各组大鼠血液中游离脂肪酸(FFA)水平及骨骼肌中甘油三酯(TG)含量,同时应用蛋白免疫印迹法检测各组大鼠骨骼肌中一磷酸腺苷活化蛋白激酶α(AMPKα)的磷酸化水平.结果 实验进行24周后,与对照组比较,发现静息组大鼠胰岛素敏感性显著降低,FFA水平及骨骼肌中TG含量明显增高,骨骼肌中AMPKα磷酸化水平降至对照组水平的48.7%;与静息组比较,运动组大鼠胰岛素敏感性及骨骼肌中AMPKα磷酸化水平均明显提高,FFA水平及骨骼肌中TG含量则显著降低;但与对照组比较,运动组大鼠FFA水平及骨骼肌中TG含量依然偏高,胰岛素敏感性及骨骼肌中AMPKα磷酸化水平仍然偏低.结论 运动干预可改善由高脂饮食诱导的IR,其治疗机制可能与降低血液中FFA水平及减轻骨骼肌中脂质异位沉积有关.

Abstract：

Objective To observe the effect of exercise on insulin resistance induced by a high fat diet and to explore the underlying mechanism.Methods Thirty healthy male Wistar rats were randomly divided into a normal control group (NC group) and a high-fat group (HF group),fed with normal chow and a high fat diet respectively.Eighteen weeks later,insulin resistance had appeared in the HF group.The HF group was then randomly subdivided into a high-fat diet control group (HC group,fed a high fat diet) and an exercise group (HE group,fed a high fat diet and subjected to swimming training for 6 weeks).After 24 weeks,an insulin sensitivity index was calculated.Serum free fatty acid (FFA) and skeletal muscle triglyceride (TG) were detected.Phosphorylation of adenosine monophosphate kinase-α (AMPKα) in skeletal muscle was detected by Western blotting.Results At twenty-four weeks the insulin sensitivity of the HC group had decreased significantly compared to the NC group.Serum FFA level and skeletal muscle TG content had both increased.Average phosphorylation of AMPKα in the HC group decreased to 48.7% of the NC group average.Compared to the HC group,insulin sensitivity and phosporylation of AMPK-α were elevated significantly in the HE group.Serum FFA level and skeletal muscle TG content were both lower.However,compared to the NC group,both serum FFA level and skeletal muscle TG content had increased in the HE group,while insulin sensitivity and phosphorylation of AMPKα had significantly decreased.Conclusions Exercise can significantly improve insulin resistance induced by a high-fat diet through decreasing serum FFA level and ectopic li-pid accumulation in skeletal muscle.     

早期应用去甲肾上腺素的液体复苏方案对脓毒性休克大鼠肺脏的作用

目的 研究早期与延迟应用去甲肾上腺素的两种液体复苏方案对脓毒性休克大鼠肺损伤的影响.方法 60只Wistar大鼠随机(随机数字法)分成4组:健康对照组(A组,n=15),休克对照组(B组,n=15),传统液体复苏组(C组,n=15),早期应用去甲肾上腺素组(D组,n=15),所有大鼠给予经口气管插管机械通气,相同呼吸机模式及参数.LPS静脉注射建立脓毒性休克大鼠模型,C组于液体复苏0.5h后应用去甲肾上腺素,D组于液体复苏同时应用去甲肾上腺素,记录各组大鼠生命体征、补液量及去甲肾上腺素用量.2h后处死大鼠,进行血气分析,HE染色观察肺组织形态学变化,ELISA检测肺泡灌洗液及血清中炎性介质的表达,检测肺组织中髓过氧化物酶、超氧化物歧化酶及丙二醛表达.计量资料以均数±标准差((x)±s)表示,采用SPSS13.0统计软件分析,组间比较采用t检验,以P＜0.05为差异具有统计学意义.结果 早期应用去甲肾上腺素与传统补液方案比较明显减少了达到目标血压所需的补液量,使氧合指数进一步改善,同时降低了血乳酸水平(P＜0.05);HE染色结果显示早期应用去甲肾上腺素使肺水肿程度明显减轻,肺组织中炎性细胞侵润程度、肺泡充血情况得到明显改善;早期应用去甲肾上腺素和传统补液方案均使血清和肺泡灌洗液中的促炎介质白介素-6、白介素-8、肿瘤坏死因子-α表达水平下调,但早期应用去甲肾上腺素使促炎介质表达下降更为明显,与传统补液比较差异具有统计学意义(P＜0.05);早期应用去甲肾上腺素仅使髓过氧化物酶表达较传统补液组及休克对照组明显下降,两种补液方案对超氧化物歧化酶和丙二醛表达均无明显改善.结论 早期应用去甲肾上腺素的液体复苏方案与传统补液方案比较从多层面改善了脓毒性休克大鼠肺损伤的程度.     

血管外肺水指数在脓毒症相关性ALI/ARDS患者液体管理中的意义

Objective The management of fluid infusion is crucial in severe sepsis/septic shock patients.The correlation of extravascular lung water index(EVLWI) versus oxygenation index ( PaO2/FiO2 ) and EVLWI versus intrathoracic blood volume index(ITBVI) were analysed in this present study. Method Totally 24 patients,admitted to the Intensive Care Unit of Second Affiliated Hospital of Zhejiang University, College of Medicine and diagnosed as severe sepsis/septic shock with acute lung injury and/or acute respiratory distress syndrome,were enrolled. ITBVI and EVLWI were detected with PiCCO technique. Correlation of EVLWI and PaO2/FiO2, ITBVI and EVLWI were analysed,respectively. Simple correlation and simple linear regression were used for statistical analysis. Results Significant negative correlation was found of EVLWI and PaO2/FiO2 ( r = - 0. 45, P ＜ 0.01).EVLWT = 14 mL/kg was defined as the cutoff value for the subgroup analysis. No correlation was found between EVLWI and PaO2/FiO2 in the subgroup with EVLWI≤ 14 mL/kg ( r = 0. 12, P = 0.243), but in the subgroup with EVLWI ＞ 14 mL/kg, significant negative correlation was found ( r = - 0. 47, P ＜ 0. 01 ). When EVLWI was higher than 14 mL/kg,EVLW should be decreased to improve oxygenation and other aspects should be taken into account. No significant correlation was found between ITBVI and EVLWI. A ITBVI value 1000 mL/m2 was also defined as the cutoff value for the subgroup analysis. No significant correlation was found in the subgroup with ITBVI≤ 1000 mL/m2( r = 0.13, P = 0.17), while significant positive correlation was found in the subgroup with ITBVI ＞ 1000 mL/m2. This result suggested that in patients of severe sepsis/septic shock with ALI/ARDS, when the blood volume is high, ITBV should be decreased to improve the oxygenation,however,it is not useful in the situation of high pulmonary vascular permeability. Conclusions Extravascular lung water has a important role in the fluid management in patients of severe sepsis/septic shock with ALI/ARDS.     

血管外肺水指数在脓毒症相关性ALI/ARDS患者液体管理中的意义

目的 通过观察严重脓毒症/脓毒性休克患者血管外肺水指数(extravascular lung water index,EVLWI)与氧合指数(PaO2/FiO2)和胸腔内血容量指数(intrathoracic blood volume index,ITBVI)的相关性,探讨血管外肺水在脓毒症相关性急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)患者液体管理中的指导意义,为脓毒症相关性ALI/ARDS患者的液体管理提供新的临床策略.方法 选择2006年4月至2008年4月浙江大学医学院附属第二医院重症医学科符合严重脓毒症/脓毒性休克伴ALI/ARDS患者24例,应用PiCCO技术监测患者胸腔内血容量指数(ITBVI)和血管外肺水指数(EVLWI),用血气分析同时监测动脉血氧分压(PaO2),以PaO2/吸入氧浓度(FiO2)计算氧合指数.比较EVLWI与PaO2/FiO2和ITBVI与EVLWI之间的相关性.采用简单相关分析法进行统计学分析.结果 EVLWI与PaO2/FiO2呈明显负相关(r=-0.45,P＜0.01).进一步以EVLWI=14 mL/kg进行分层分析,当EVLWI≤14 mL/kg时,两者无明显相关性(r=0.12,P=0.243);当EVLWI＞14 mL/kg时,两者呈明显负相关(r=-0.47,P＜0.01).这可以提示对严重脓毒症/脓毒性休克伴ALI/ARDS患者,EVLW不是影响氧合的唯一因素,当EVLWI＞14 mL/kg时,可以通过降低EVLW来改善氧合,但更应综合考虑影响氧合指数的各种因素.ITBVI与EVLWI无明显相关性(r=0.02,P=0.84).进一步以ITBVI=1000 mL/m2进行分层分析,当ITBVI≤1000 mL/m2时,两者无明显相关性(r=0.13,P=0.17);当ITBVI＞1000 mL/m2时,两者呈明显正相关(r=0.40,P＜0.01).这提示我们对于脓毒症相关性ALI/ARDS,当ITBVI＞1000mL/m2时,可以通过降低ITBV来降低EVLW,但对于肺毛细血管通透性增高症引起的EVLW,不能通过降低ITBV来降低.结论 EVLW在脓毒症相关性ALI/ARDS的液体管理中具有重要指导意义.     

The effect of alloxan diabetes on experimental cholesterol atherosclerosis in the rabbit. IV. The effect of insulin therapy on the inhibition of atherosclerosis in the alloxan-diabetic rabbit

Experiments were undertaken to ascertain whether the previously demonstrated inhibition of the development of experimental aortic atherosclerosis in alloxan-diabetic rabbits fed cholesterol was due to the injection of alloxan per se or to the existence of the diabetic state produced by alloxan. It was established that, by treating the diabetic state with insulin, the diabetic state could be ameliorated and the inhibitory effect obviated. It was therefore concluded that the inhibitory phenomenon was not due to the injection of alloxan per se but that it was associated with one or more factors that characterize the alloxan diabetic state in the rabbit and that are reversible by insulin therapy. In the course of the experiment it was demonstrated that the inhibitory effect was apparent in cholesterol-fed diabetic rabbits whether or not their diet was supplemented with vegetable oil. The previously reported metabolic abnormalities of the diabetic animals were confirmed. It was established that suitable treatment of the cholesterol-fed diabetic animals with insulin would bring all the metabolic aberrations, including those of the serum lipids, into reasonably close correspondence with those observed in non-diabetic rabbits fed cholesterol.