内毒素对SD大鼠急性肝功能衰竭模型血糖代谢影响的研究

研究D氨基半乳糖(D-GaLN)/脂多糖,内毒素(LPS,endotoxin)联合诱导的急性肝功能衰竭大鼠模型中,内毒素对血糖及其调节激素的影响。方法:24只雄性健康成年SD大鼠,随机分成4组,每组6只,组Ⅰ腹腔注射生理盐水;组Ⅱ腹腔注射400mg/kgD-GalN;组Ⅲ腹腔注射400mg/kgD-GalN 5μg/100gLPS;组Ⅳ腹腔注射400mg/kgD-GalN 50μg/100gLPS。LPS给予前1h、给于后2、6h监测血糖,在6h股静脉取血分离大鼠血清,检测肝功能、乳酸、胰岛素、胰高血糖素;取肝组织苏木素-伊红(HE)染色进行病理学分析。结果:组Ⅲ、Ⅳ均可以成功构建急性肝功能衰竭的模型;组Ⅰ与组Ⅱ比较血浆胰岛素,胰高血糖素水平无显著差异;组Ⅲ、Ⅳ与组Ⅰ比较血浆胰岛素、胰高血糖素均显著升高(P<0.05);组Ⅳ与组Ⅰ、Ⅱ、Ⅲ比较血糖明显降低,乳酸显著升高(P<0.05)。结论:急性肝功能衰竭的模型中有血糖调节机制的异常,大剂量的内毒素导致低血糖的发生。     

新生大鼠肝细胞脾内移植联合鼠肝再生增强因子治疗大鼠急性肝衰竭的疗效与免疫学机制

目的探讨新生大鼠肝细胞脾内移植联合重组鼠肝再生增强因子（rALR）治疗大鼠急性肝衰竭的疗效与免疫学机制。方法采用D-氨基半乳糖（1．2 g／kg）诱导并建立大鼠急性肝衰竭模型,36 h后随机分为6组：Ⅰ组：模型对照组;Ⅱ组：经脾脏注射等渗盐水1 ml,腹腔注射等渗盐水1 ml／d;Ⅲ组：经脾脏注射rALR 1 ml（50μg／kg）,腹腔注射rALR 1 ml（50μg·kg^-1·d^-1）;Ⅳ：经脾脏移植2×10^7同种异体新生大鼠肝细胞,腹腔注射等渗盐水1 ml／d;Ⅴ组：经脾脏移植2×10^7同种异体新生大鼠肝细胞,腹腔注射rALR 1 ml（50μg·kg^-1·d^-1）;Ⅵ组：经脾脏移植2×10^7同种异体新生大鼠肝细胞,腹腔注射环孢菌素1 ml（10 mg·kg^-1·d^-1）。观察大鼠每天存活率;术后第1、5天及2周处死大鼠以获取肝、脾组织,观察脾内移植肝细胞的组织学改变;在术前、术后第1、2、5、12天采集静脉血,采用放射免疫法测定血清IL-1β和TNFα的浓度。结果Ⅰ、Ⅱ和Ⅲ组大鼠存活时间差异无统计学意义,Ⅳ组有部分大鼠长期存活,2周存活率为33％,Ⅴ组大鼠2周存活率显著高于Ⅳ组,而与Ⅵ组大鼠2周存活率比较差异无统计学意义。Ⅳ、Ⅵ组脾内移植的肝细胞可存活5～7 d,Ⅴ组脾内移植肝细胞可存活至2周以上。术后第1天,Ⅳ组血清IL-1β水平显著高于Ⅴ组和Ⅵ组（P〈0．05）;术后第5天,Ⅳ组血清IL-1β水平仅与Ⅵ组差异有统计学意义（P〈0．05）。术后第1天,TNFα的浓度在Ⅱ组显著高于Ⅳ、Ⅴ、Ⅵ组（P〈0．05）。结论新生大鼠肝细胞脾内移植与rALR联合治疗大鼠急性肝衰竭有一定疗效,可提高D-氨基半乳糖诱导肝衰竭大鼠的存活率;移植肝细胞在脾脏可存活2周以上,其机制可能与促进肝细胞再生、预防移植肝细胞凋亡及轻微抑制细胞免疫有关。     

榄香烯和VEGF多克隆抗体联合应用对C_6胶质瘤增殖的抑制作用

目的探讨榄香烯和VEGF多克隆抗体联合应用对昆明小鼠皮下C6胶质瘤的抑制作用。方法建立昆明小鼠皮下C6胶质瘤模型,将32只接种成瘤后的小鼠随机分成4组,每组8只,Ⅰ组生理盐水、Ⅱ组榄香烯、Ⅲ组VEGF多克隆抗体、Ⅳ组榄香烯和VEGF多克隆抗体。治疗后定期测量肿瘤的大小,计算抑制率,镜下观察肿瘤组织病理切片,流式细胞仪检测肿瘤细胞凋亡率。结果Ⅱ组、Ⅲ组、Ⅳ组的抑制率分别为（43.2&#177;3.6）%、（41.3&#177;2.9）%、（51.9&#177;4.1）%,Ⅳ组的抑制率低于Ⅱ组和Ⅲ组（P〈0.05）。实验组肿瘤标本见到较多的坏死灶,其中肿瘤细胞可见较多的核破裂,肿瘤组织坏死程度和血管的减少量Ⅳ组多于Ⅲ组和Ⅱ组。Ⅰ组、Ⅱ组、Ⅲ组、Ⅳ组细胞凋亡率分别为（0.46&#177;0.19）%、（12.9&#177;1.70）%、（11.7&#177;1.70）%、（19.4&#177;1.32）%,Ⅳ组较Ⅱ组、Ⅲ组的凋亡率高（P〈0.05）。结论榄香烯和VEGF多克隆抗体联合应用能更好抑制肿瘤组织的生长,具有协同的作用。     

D-氨基半乳糖大鼠急性肝衰竭并发内毒素血症对糖代谢的影响及其机制

目的：探讨大鼠急性肝功能衰竭时内毒素血症对糖代谢的影响及其机制。方法：利用D-氨基半乳糖（D—GaLN）诱导建立大鼠肝衰竭模型,24只雄性Wistar大鼠随机分为对照组（等渗盐水）、低剂量组（100mg／kgD—GaLN）、中剂量组（200mg／kgD—GaLN）、高剂量组（300rag／kgD—GaLN）,收集各组血清和肝组织,检测内毒素、血糖、肝功能,采用半定量PCR方法检测大鼠肝组织中葡萄糖-6-磷酸酶（G6P）和磷酸烯醇丙酮酸羧激酶（PEPCK）的基因转录,6-磷酸葡萄糖法检测葡萄糖激酶（GCK）活性。结果：200mg／kg以上剂量D—GaIN可诱导大鼠急性肝衰竭,并出现低糖血症,内毒素水平随着D—GaIN浓度升高而升高;实验组大鼠GCK活性较对照组均升高,而G6P、PEPCK的mRNA表达随D—GaIN浓度升高而下调。结论：急性肝功能衰竭大鼠并发内毒素血症可能通过促进糖酵解、抑制糖异生导致低血糖的发生。     

美蓝尿流动力学检查在拟诊合并泌尿系统畸形女性持续性尿失禁诊断中的应用

对18例拟诊合并泌尿系统畸形的女性持续性尿失禁患者进行美蓝尿流动力学检查,膀胱充盈期会阴部有无色尿液漏出者为美蓝尿动力学检查阳性（Ⅰ组）,有蓝色尿液漏出者为阴性（其中经阴道漏出蓝色尿液者为Ⅱ组,经尿道漏出蓝色尿液者为Ⅲ组）。结果显示,Ⅰ组4例,Ⅱ组4例,Ⅲ组10例;Ⅰ、Ⅱ、Ⅲ组最大膀胱容量分别为（217.5&#177;27.5）、（107.5&#177;35.9）、（357.0&#177;134.3）ml,膀胱顺应性分别为（42.6&#177;12.）、（30.6&#177;8.4）、（37.3&#177;20.1）ml/cmH2O,最大逼尿肌压力分别为（36.0&#177;15.3）、（16.5&#177;4.9）、（40.1&#177;18.0）cmH2O,残余尿量分别为（2.5&#177;2.9）、（3.8&#177;4.8）、（25.0&#177;45.0）ml;三组最大膀胱容量相比,P〈0.05,其余指标相比,P〉0.05。认为美蓝尿流动力学检查在疑有泌尿系统畸形的女性持续性尿失禁的诊断和鉴别诊断中有一定的应用价值。     

负载肝癌抗原的树突状细胞疫苗对SCID荷瘤鼠的抑瘤作用观察

采用人外周血淋巴细胞腹腔注射法建立人外周血淋巴细胞—严重联合免疫缺陷（Hu-PBL-SCID）鼠模型。随机分为四组：Ⅰ组尾静脉注射mRNA未致敏的树突状细胞（DC）疫苗,Ⅱ组注射抗CD4＋、CD8＋＋mRNADC,Ⅲ组为DC,Ⅳ组为PBS,每周1次,共2次,然后接种2&#215;106肝癌细胞HepG-2,观察鼠成瘤率、成瘤潜伏期、肿瘤体积以及测定特异性细胞毒淋巴细胞（CTL）活性;流式细胞术检测体内种植瘤的细胞周期;用ELISA法检测鼠血清中是否有人IgG。结果鼠血清中均有人IgG,Hu-PBL-SCID嵌合模型重建成功,各组小鼠间成瘤率无明显差异,但Ⅰ组成瘤潜伏期延长,肿瘤生长缓慢,2周后肿瘤体积明显小于Ⅱ、Ⅲ、Ⅳ组（P〈0.05）,Ⅰ组脾淋巴细胞对HepG-2有特异性杀伤效应。Ⅰ组HepG-2有75.82%&#177;4.78%处于G0/G1期,13.54%&#177;2.55%处于S期,10.64%&#177;2.36%处于G2/M期,与Ⅱ、Ⅲ、Ⅳ比较,P〈0.05。认为负载肝癌抗原的DC疫苗体内能诱导产生明显的抑瘤作用。     

腺苷蛋氨酸对酒精性脂肪肝大鼠治疗效果及机制的研究

目的观察腺苷蛋氨酸（SAM）对酒精性肝损伤的防治作用及机制。方法将48只SD大鼠随机分为对照组（Ⅰ组）、模型组（Ⅱ组）及SAM低剂量组（Ⅲ组）、SAM高剂量组（Ⅳ组）,每组12只。除对照组外,其余三组给予酒精、鱼油灌胃配合高脂饮食诱导酒精性肝损伤,4周后Ⅰ、Ⅱ组腹腔注射生理盐水,Ⅲ、Ⅳ组分别腹腔注射SAMl00mg／kg、200mg／kg,第8周均处死。测定血浆总同型半胱氨酸（tHcy）浓度、血清丙氨酸转移酶（ALT）、天冬氨酸转移酶（AST）浓度;测定肝匀浆丙二醛（MDA）、超氧化物歧化酶（SOD）和还原型谷胱甘肽（GSH）含量,行肝脏病理组织学检查。结果与Ⅰ组比较,Ⅱ组肝损伤明显,表现为ALT、AST、tHcy水平升高,肝脂肪变性,MDA含量增加,SOD和GSH水平下降;Ⅲ、Ⅳ组MDA降低、GSH升高,但tHcy水平和肝组织SOD含量无显著变化,Ⅲ、Ⅳ组间无明显差别。结论SAM可防治大鼠酒精性肝损伤,其机制可能与调节肝脏内氧化抗氧化系统的平衡有关;SAM对血浆tHcy水平无明显影响。     

肺结核患者血清纤维化指标与肺通气功能的相关性研究

目的 探讨血清纤维化指标作为肺结核患者肺纤维化诊断及治疗的实验室指标的可行性.方法 测定所选病例的肺功能及血清纤维化指标,根据肺功能结果分为肺功能基本正常组[1]（A组,20例）、轻度减退组（B组,35例）、显著减退组（C组,46例）、严重减退组（D组,29例）.结果 A组血清Ⅲ型前胶原（PⅢP）平均值为16±2 ng/ml,血清透明质酸（HA）、血清层连蛋白（LN）平均水平分别为（88±6）、（98±15）ng/ml,血清Ⅳ型胶原（cⅣ）均值为（120±26） ng/ml;B组PⅢP均值为（19.5±4）ng/ml,HA均值为（92.6±12）ng/ml, LN均值为（102±16）ng/ml,cⅣ均质为（141±31）ng/ml;C组PⅢP均值为（25.4±4）ng/ml,HA均值为（95±21）ng/ml,LN均值为（111.8±30）ng/ml,cⅣ均质为（158±39）ng/ml;D组PⅢP均值为（28.9±5）ng/ml,HA均值为（108±18）ng/ml,LN均值为（132±37）ng/ml,cⅣ均质为（193±46）ng/ml.四组中cⅣ、PⅢP的平均值经方差分析F值分别为17.85、55.9,说明4组cⅣ、PⅢP均值有显著性差异,经F检验各组间有显著性差异;4组中HA、LN的均值经方差分析F值分别为7.38、8.69,具有显著性差异,经F检验各组间无显著性差异;cⅣ、PⅢP、HA、LN分别与一秒钟用力呼气容积率（FEV1.0%）做相关回归分析P值分别为0.015、0.009、0.093、0.12,说明cⅣ、PⅢP与肺功能存在直线关系,而HA、LN则不具有.结论 血清纤维化指标与肺结核患者的肺功能状态有相关性,在一定程度上反应了肺纤维化程度,其中cⅣ、PⅢP与肺纤维化程度的相关性最强.     

肿瘤坏死因子α对暴发性肝衰竭小鼠肠上皮细胞紧密连接蛋白表达的影响

目的 研究TNFα对暴发性肝衰竭（FHF）小鼠大肠上皮细胞紧密连接蛋白occludin表达的影响。方法 采用D-氨基半乳糖（GaIN）和内毒素（LPS）联合腹腔注射（ip）制备FHF小鼠动物模型,并设立TNFα组（TNFα10μs／kg,ip）,TNFα抗体组（注射LPS和GaIN前30min尾静脉注射TNFd抗体100μg/只）。在不同的时间点（6h,9h）处死动物,应用免疫组织化学技术、Westernblot及实时定量PCR检测各组小鼠大肠上皮细胞紧密连接蛋白occludin表达的变化。结果 在生理盐水（NS）对照组,几乎整张切片上均可见到沿大肠黏膜上皮细胞膜顶端呈线性分布的occludin阳性染色,但FHF组及TNFα组小鼠的阳性染色较之明显减弱,TNFα抗体组occludin的阳性反应与Ns对照组比较无明显减弱。Westernblot结果与免疫组织化学结果相一致,FHF组及TNFα组小鼠9h时occludin蛋白含量明显下降,与NS对照组相比差异有统计学意义（0．36±0．05,0．48±0．02比0．71±0．09,P〈0．05）,TNFα抗体组与NS对照组相比差异无统计学意义（0．74±0．03比0．71±0．09,P〉0．05）。实时定量PCR结果显示,FHF组与TNFα组小鼠6h时occludinmRNA水平最低,与NS对照组相比差异有统计学意义（0．72±0．04,0．81±0．03比1．00±0．05,P〈0．05）,TNFα抗体组与Ns对照组相比差异无统计学意义（1．01±0．10比1．00±0．05,P〉0．05）。结论 在小鼠暴发性肝衰竭过程中,TNFα介导大肠上皮细胞间紧密连接蛋白occludin表达的下降。     

99mTc-MDP联合胶体磷酸铬32P与单一疗法对大鼠佐剂型关节炎治疗效果比较

目的用^99mTc-亚甲基二膦酸盐（^99mTc-MDP）联合胶体磷酸铬^32P治疗大鼠佐剂型关节炎，探讨其疗效并与单一使用^99mTc-MDP或胶体磷酸铬^32P治疗进行比较。方法利用佐剂诱导SD大鼠的关节炎模型（AA），给予胶体磷酸铬^32P踝关节腔内注射以及^99mTc-MDP腹腔注射，在不同的时间点观察大鼠左踝关节的左右径宽度、血清肿瘤坏死因子（TNF）和白细胞介素-1β（IL-1β）水平及关节病理的变化。结果联合治疗组大鼠左踝关节左右径宽度较^32P胶体治疗组小[第4周（7．11±0．34）mm vs（7．57±0．29）mm，P〈0．01]。联合治疗较^32P胶体治疗更能有效地降低血清TNF[第4周时（1．6±0．4）ng／ml vs（2．0±0.3）ng／ml，P〈0．051和IL-1β[第4周时（0．271±0．033）ng／ml vs（0.308±0.024）ng／ml，P〈0．05；第6周时（0．209±0．023）ng／ml vs（0．255±0．016）ng／ml，P〈0.01]的水平。在病理检查上，联合治疗组滑膜增生程度较^99mTc-MDP治疗组轻，而炎细胞浸润程度较^32P胶体治疗组轻。结论^99mTc-MDP联合胶体磷酸铬^32P治疗大鼠佐剂型关节炎较单用^99mTc-MDP或胶体磷酸铬^32P治疗效果更好。     

甘氨酸对内毒素性肝损害保护作用的实验研究

目的探讨甘氨酸(Gly)对内毒素(LPS)性肝损害的保护机制。方法BABL／c小鼠随机分为两组,LPS组经腹腔注射10 mg／kg的LPS,Gly组在注射相同剂量LPS前3 d开始喂饲含5％Gly的饲料。光镜观察组织病理学改变、免疫组织化学法检测Toll样受体4(TLR4)表达水平；酶联免疫吸附法检测血浆肿瘤坏死因子(TNF)α、白细胞介素10(IL-10)浓度及逆转录聚合酶链反应检测肝组织中TNFα、IL-10及TLR4的mRNA表达水平。结果Gly能明显提高小鼠存活率,肝脏病理损害程度减轻；Gly组TNFα水平显著低于LPS组,差异有统计学意义[(1852.80±126.64)pg／ml对(708.83±51.29)pg／ml,P＜0.05]；Gly组IL-10增加且高峰前移,与LPS组比较差异有统计学意义[(418.64±38.86)pg／ml对(344.09±31.70)pg／ml,P＜0.05]；Gly组肝组织中TNFα及TLR4表达也明显减弱,IL-10表达明显增强,与LPS组比较差异均有统计学意义[分别为TNFα：A值1.59±0.14对0.91±0.11；TLR4：A值0.97±0.12对0.53±0.11；IL-10：A值0.62±0.08对1.06±0.15；P值均＜0.05]。结论Gly能明显减轻LPS所致的肝损害,其机制可能与其下调肝脏各种细胞的TLR4表达,同时上调IL-10的水平有关。     

Novel Carboxamide Derivative (IS-741) Attenuates Lung Injury in Rats with Cerulein-Induced Pancreatitis Complicated by Endotoxemia

The therapeutic effects of an intravenouslyinjected carboxamide derivative (IS-741) on lung injurywere studied in rats with cerulein-induced pancreatitiscomplicated by endotoxemia. Pancreatitis was induced by four intramuscular injections of cerulein(50 g/kg at 1-hr intervals). Pancreatitis rats wereinjected intraperitoneally with 10 mg/kg oflipopolysaccharide (LPS) 6 hr following the firstcerulein injection as a challenge of endotoxemia. Ratswere divided into four groups: group I, pancreatitiswith LPS; group II, pancreatitis with LPS treated witha continuous intravenous injection of IS-741 at 0.03 mg/kg/hr); group III, pancreatitis withLPS treated with a continuous intravenous injection ofIS-741 at 0.3 mg/kg/hr); and group IV, pancreatitis withLPS treated with a continuous intravenous injection of IS-741 at 3 mg/kg/hr). IS-741 wasadministered 30 min before the endotoxemia challenge.Intense mononuclear cell infiltration and lunghemorrhage occurred in untreated pancreatitis rats withLPS (group I), but hemorrhage was not seen in group IVrats receiving a continuous injection of IS-741 shortlybefore the induction of endotoxemia. The IS-741- treatedrats (groups II, III, and IV) had lower serum concentrations of cytokine-induced neutrophilchemoattractant (CINC), as well as fewer pulmonaryinfiltrates immunoreactive for CINC or Mac-1(CD11b/CD18). The number of neutrophils infiltrating thelung in groups II, III, and IV was significantlylower than that of group I. Conversely, CINC productionby bronchoalveolar macrophages in vitro were stimulatedby LPS but were reduced by the presence of IS-741. The carboxamide derivative IS-741 effectivelyprevented pancreatitisassociated lung injury followingthe challenge of endotoxemia.     

In vivo effects of Chinese herbal recipe, Danshaohuaxian, on apoptosis and proliferation of hepatic stellate cells in hepatic fibrotic rats

AIM: To investigate the effects of Danshaohuaxian (DSHX), a Chinese herbal recipe, on the apoptosis and cell cycles of hepatic stellate cells (HSCs) in rat hepatic fibrosis and its possible mechanisms. METHODS: Seventy-six male Wistar rats were randomly divided into normal control group, hepatic fibrosis group, non-DSHX-treated group and DSHX-treated group. Except for the normal control group, rat hepatic fibrotic models were induced by subcutaneous injection of carbon tetrachloride (CCl4), drinking alcohol, giving diet of hyperlipid and hypoprotein for 8 wk. When the hepatic fibrotic models were produced, 12 rats of hepatic fibrosis group (15 rats survived, others died during the 8 wk) were sacrificed to collect blood and livers. HSCs were isolated from the other 3 rats to detect the apoptotic index (AI) and cell cycles by flow cytometry. DSHX was then given to the DSHX-treated group (1.0 g/kg, PO, daily) for 8 wk. At the same time, normal control group and non-DSHX-treated group were given normal saline for 8 wk. At end of the experiment, some rats in these three groups were sacrificed to collect blood and livers, the other rats were used for HSC isolation to detect the apoptotic index (AI) and cell cycles. Then the liver index, serum hyaluronic acid (HA) and alanine aminotransferase (ALT), degree of hepatic fibrosis, urinary excretion of hydroxyproline (Hyp) and expression of collagen types Ⅰ and Ⅲ (COL Ⅰ and Ⅲ) in these four groups were detected respectively. RESULTS: Compared with the indexes of the hepatic fibrosis group and non-DSHX-treated group, the DSHX-treated group revealed a liver index of (0.0267±0.0017 vs 0.0423±0.0044, 0.0295±0.0019, P<0.05), levels of serum HA (200.78±31.71 vs 316.17±78.48, 300.86±72.73, P<0.05) and ALT(93.13±5.79 vs 174.5±6.02, 104.75±6.54, P<0.01), and stage of hepatic fibrosis (1.30 vs 4.25, 2.60, P<0.01) all reduced. The urinary excretion of Hyp increased (541.09±73.39 vs 62.00±6.40, 182.44±30.83, P<0.01), the COL Ⅰ and Ⅲ expression decreased (COL I: 1.07±0.96 vs 4.18±2.26, 3.22±1.44, P<0.01; COL Ⅲ: 1.09±0.58 vs 3.04±0.62, 2.23±0.58, P<0.01), the HSCs apoptotic index of HSCs (7.81±0.47 vs 1.63±0.25, 1.78±0.4, P<0.05) and the ratio of G0-G1 phase cells increased (94.30±1.33 vs 62.27±17.96, 50.53±2.25, P<0.05). The ratios of S-phase cells (3.11±1.27 vs 9.83±1.81, 11.87±1.9, P<0.05) and G2-M phase cells (2.58±0.73 vs 23.26±10.95, 13.60±1.15, P<0.01) declined. CONCLUSION: DSHX capsule shows certain therapeutic effects on hepatic fibrosis in rats and inhibits abnormal deposition of COL I and III in rat livers by promoting the apoptosis of HSCs and preventing their proliferation.     

Effect of 1,25-dihydroxyvitamin D3 on preventing allograft from acute rejection following rat orthotopic liver transplantation

AIM: To study the mechanism and the preventive role of 1,25-dihydroxyvitamin D3 in acute rejection following orthotopic liver transplantation.METHODS: Rats were randomly divided as donors or recipients for orthotopic liver allotransplantation model. Four groups were designed in the study, Group Ⅰ: syngenic control(Wistar to Wistar); Group Ⅱ: acute rejection (SD to Wistar);Group Ⅲ: acute rejection treated with cyclosporine A, and Group Ⅳ: acute rejection treated with 1,25-(OH)2D3. Liver function, rejection activity index and mRNA of IFN-γ, IL-10 intragraft in recipients were measured on day 1, 5, 7, 15,30 posttransplant for assessing graft function, severity of acute rejection and immune state of recipients.RESULTS: Survival time of recipients in Group Ⅳ was significantly prolonged (4/6 recipients survived for over 100 days. vs Group Ⅱ, P&lt;0.001; vs Group Ⅲ, P&gt;0.05). After treatment with 1,25-(OH)2 D3, mean value of all the assay tested on each experimental time was compared, liver function in group IV was significantly improved (AST 127&#177;41U/L-360&#177;104U/L, BIL 13&#177;5mmol/l-38&#177;11mmol/l; vs Group Ⅱ, P&lt;0.05; vs Group Ⅲ, P&gt;0.05. Rejection activity index was significantly decreased (0-3.3&#177;1.6; vs Group Ⅱ, P&lt;0.05;vs Group Ⅲ, P&gt;0.05). Level of hepatic IFN-γ, mRNA in group IV was decreased, while level of hepatic IL-10 mRNA was increased (vs Group Ⅱ, P&lt;0.05; vs Group Ⅲ, P&gt;0.05).CONCLUSION: Our results indicated that 1,25-(OH)2D3 induced the secretion of oltokine toward to Th2 type, which would alleviate acute rejection, protect liver function and prolong survival of recipient after orthotopic liver transplantation.     

Intrarenal aminopeptidase N inhibition augments natriuretic responses to angiotensin III in angiotensin type 1 receptor-blocked rats

The renal angiotensin angiotensin type 2 receptor has been shown to mediate natriuresis, and angiotensin III, not angiotensin II, may be the preferential angiotensin type 2 receptor activator of this response. Angiotensin III is metabolized to angiotensin IV by aminopeptidase N. The present study hypothesizes that inhibition of aminopeptidase N will augment natriuretic responses to intrarenal angiotensin III in angiotension type 1 receptor-blocked rats. Rats received systemic candesartan for 24 hours before the experiment. After a 1-hour control, cumulative renal interstitial infusion of angiotensin III at 3.5, 7, 14, and 28 nmol/kg per minute (each dose for 30 minutes) or angiotensin III combined with aminopeptidase N inhibitor PC-18 was administered into 1 kidney. The contralateral control kidney received renal interstitial infusion of vehicle. In kidneys infused with angiotensin III alone, renal sodium excretion rate increased from 0.05+/-0.01 micromol/min in stepwise fashion to 0.11+/-0.01 micromol/min at 28 nmol/kg per minute of angiotensin III (overall ANOVA F=3.68; P<0.01). In angiotensin III combined with PC-18, the renal sodium excretion rate increased from 0.05+/-0.01 to 0.32+/-0.08 mumol/min at 28 nmol/kg per minute of angiotensin III (overall ANOVA F=6.2; P<0.001). The addition of intrarenal PD-123319, an angiotensin type 2 receptor antagonist, to renal interstitial angiotensin III plus PC-18 inhibited the natriuretic response. Mean arterial blood pressure and renal sodium excretion rate from control kidneys were unchanged by angiotensin III +/- PC-18 + PD-123319. Angiotensin III plus PC-18 induced a greater natriuretic response than Ang III alone (overall ANOVA F=16.9; P=0.0001). Aminopeptidase N inhibition augmented the natriuretic response to angiotensin III, suggesting that angiotensin III is a major agonist of angiotensin type 2 receptor-induced natriuresis.     

Effect of resveratrol on microcirculation disorder and lung injury following severe acute pancreatitis in rats

AIM: To investigate the mechanism of resveratrol underlying the microcirculation disorder and lung injury following severe acute pancreatitis (SAP). METHODS: Twenty-four rats were divided into 3 groups (SAP, sham and resveratrol groups) randomly. SAP model was established by injecting 4% sodium taurocholate l mL/kg through puncturing pancreatic ducts. Sham (control) group (8 rats) was established by turning over the duodenum. Resveratrol was given at 0.1 mg/kg b.m. intraperitoneally. Rats were sacrificed 9 h after SAP was induced. Blood samples were obtained for hemorrheological examination. Lung tissues were used for pathological observation, and examination of microvascular permeability, dry/wet ratio and myeloperoxidase (MPO) activity. Gene expression of intercellular adhesion molecule-1 (ICAM-1) was detected by RT-PCR. RESULTS: Compared with SAP group, resveratrol relieved the edema and infiltration of leukocytes in the lungs. Resveratrol improved markers of hemorrheology: high VTB (5.77±1.18 mPas vs9.49±1.34 mPas), low VTB (16.12±3.20 mPas vs30.91±7.28 mPas), PV (4.69±1.68 mPas vs 8.00±1.34 mPas), BSR (1.25±0.42 mm/h vs50.03±0.03 mm/h), VPC (54.67±3.08% vs 62.17±3.39%), fibrinogen (203.2?7.8 g/ L vs 51.3±19.1 g/L), original hemolysis (0.45±0.02 vs 0.49±0.02), and complete hemolysis (0.41±0.02 vs 0.43±0.02) (P<0.05). Resveratrol decreased the OD ratio of ICAM-1 gene (0.800±0.03 vs 1.188±0.10), dry/wet ratio (0.74±0.02 vs 0.77±0.03), microvascular permeability (0.079±0.006 vs 0.112±0.004) and MPO activity (4.42±0.32 vs 5.03±0.51) significantly (P<0.05). CONCLUSION: Resveratrol can improve the microcirculation disorder of the lung by decreasing leukocyte-endothelial interaction, reducing blood viscosity, improving the decrease of blood flow, and stabilizing erythrocytes in SAP rats. It may be a potential candidate to treat SAP and its severe complications (ALI).     

Pathophysiology of tricuspid insufficiency: analysis of the motion of the tricuspid valve annulus using 2-dimensional echocardiography

We investigated tricuspid annular motion in patients with pulmonary hypertension and in normal controls to determine the greatest minimal diameter and percentage shortening of the tricuspid annulus required for functional tricuspid regurgitation. 73 patients were studied by 2-dimensional echocardiography: a control group of 30 patients (group I); 43 patients had pulmonary hypertension, 9 of whom were still in sinus rhythm (group II), the other 34 patients had atrial fibrillation. 19 of these showed competent tricuspid valve with contrast echocardiography (group III), whereas the 15 remaining patients had functional tricuspid regurgitation (group IV). An analysis of shape and position changes of tricuspid annulus during the heart cycle was performed. The maximal diameter (mm/m2) in the apical 4 chamber view was in group I 17.5 +/- 1.4, in group II 20.7 +/- 3.2 (vs. group I p less than 0.05), in group III 19.0 +/- 3.4 (vs. group II NS) and in group IV 25.7 +/- 6.0 (vs. group III p less than 0.001). The values for the minimal annular diameter (mm/m2) were in group I 13.7 +/- 1.2, in group II 17.4 +/- 3.5 (vs. group I p less than 0.01), in group III 16.6 +/- 3.3 (vs. group II NS) and in group IV 23.6 +/- 5.7 (vs. group p less than 0.001). The percent decrease (%) in group I was 21.5 +/- 3.3, in group II 17.0 +/- 6.9 (vs. group I p less than 0.05), in group III 12.8 +/- 4.7 (vs. group II p less than 0.05) and in group IV 7.9 +/- 3.4 (vs. group III p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)