慢性乙型肝炎患者肝组织内诱导型一氧化氮合酶的表达与肝组织病变的关系

目的 探讨诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)在慢性乙型肝炎(chronic hepatitis B,CHB)患者肝组织内的表达及与肝组织病变的关系和临床意义.方法 应用免疫组织化学法检测74例CHB患者肝组织内iNOS的表达和分布情况,并分析其与患者肝功能、HBeAg、HBV DNA及肝组织病理分级和分期的关系.结果 CHB患者组与正常对照组相比,肝组织内iNOS表达明显增加(P＜0.01).CHB患者肝组织内iNOS表达强度与ALT水平、肝组织炎症程度和纤维化分期之间呈显著正相关(r=0.601,P=0.000;r=0.660,P=0.000;r=0.507,P=0.000).结论 CHB患者肝组织内iNOS表达显著增高,并随着肝脏炎症和纤维化程度的加重表达增强,与CHB病变进展密切相关.     

慢性乙型肝炎患者肝功能及血清HBeAg和HBV DNA载量与肝组织病理相关性的研究

目的 探讨慢性乙型肝炎患者肝功能、HBeAg及HBV DNA水平与肝组织病理炎症分级和纤维化分期的关系.方法 选择233例慢性乙型肝炎患者进行肝穿病理学检查,同时所有患者检测HBV DNA、HBeAg及肝功能,比较患者的肝功能、HBeAg及HBV DNA水平在不同病理炎症分级及纤维化分期中的差异情况.结果 不同的炎症分级患者中,ALT以C3组最高,G0～1组最低,各组间比较差异有统计学意义(P =0.016);TBil以G4组最高,G0～1组最低,各组间比较差异有统计学意义(P=0.000);HBV DNA载量各组间差异无统计学意义.不同的纤维化分期患者中,ALT各组间比较差异无统计学意义;TBil以S4组最高,S2组最低,各组间比较差异有统计学意义(P=0.039);HBV DNA载量各组间差异无统计学意义.炎症分级为G3～4的患者比例在HBeAg阳性组与阴性组差异无统计学意义.纤维化分期S3～4的患者比例在HBeAS阳性组(38%)比HBeAg阴性组(53%)低,两组差异有统计学意义(P=0.025).结论 慢性乙型肝炎患者血清HBV DNA水平的高低不能反映其肝脏炎症及纤维化程度,HBeAg阴性慢乙肝患者肝组织纤维化程度较高,TBil水平与肝组织炎症分级及纤维化分期均有良好的相关性,ALT水平与炎症分级有一定的关联性,但与纤维化分期无关.     

HBeAg阴性慢性乙型肝炎患者血清病毒载量与肝组织学改变的关系

目的 探讨HBeAg阴性慢性乙型肝炎患者血清HBV DNA水平与肝组织损害的关系.方法 以HBeAg阳性慢性乙型肝炎病例为对照,回顾分析HBeAg阴性慢性乙型肝炎患者血清HBVDNA水平与肝组织病理炎症分级、纤维化分期之间的关系.结果 HBeAg阴性与阳性组HBV DNA 平均含量分别为（5.38±1.27）log10拷贝/ml和（6.80±1.18）log10拷贝/ml,差异有统计学意义（P〈0.01）.与HBeAg阳性组比较,HBeAg阴性组肝组织炎症分级及纤维化分期较高（P〈0.01）.HBeAg 阴性患者HBV DNA水平与肝组织炎症分级及纤维化分期呈正相关（P〈0.01）.结论 HBeAg阴性慢性乙型肝炎病毒载量低,乙肝病毒载量与肝损害呈正相关.     

慢性乙型肝炎患者血清维生素E水平与肝组织病理的关系研究

目的 探讨慢性乙型肝炎(CHB)患者血清维生素E水平与肝组织病理的关系.方法 选择66例慢性乙型肝炎患者进行肝穿刺病理学检查,健康对照组10例.化学比色法检测血清维生素E表达水平,同时检测HBV DNA、HBeAg及肝功能.结果 与正常对照组相比,慢性乙型肝炎患者血清维生素E水平明显降低(P<0.01);HBeAg阳性组与HBeAg阴性组比较,血清维生素E水平无明显差别(P0.05).CHB患者血清维牛素E水平与肝脏组织炎症呈负相关关系(r=-0.451,P<0.05),而与肝脏组织纤维化程度无明显相关(r=0.02,P0.05).结论 维生素E作为体内重要的抗氧化剂,参与了慢性乙型肝炎的炎症过程.在肝脏炎症过程中,适当补充维生素E,可能有助于缓解病情.     

慢性乙型肝炎患者血清HBsAg水平与肝脏炎症和纤维化程度相关性研究

目的 探讨慢性乙型肝炎患者HBsAg水平与肝脏炎症和纤维化的关系.方法 301例确诊为慢性乙型肝炎的患者纳入研究,同时进行肝脏活检术检查和生物化学、铁蛋白、血清HBsAg、HBV DNA定量检测.Spearman等级相关分析血清HBsAg水平与肝脏炎症分级和纤维化分期间的关系;logistic回归分析法分析相关指标的诊断意义,受试者工作曲线法评价血清HBsAg水平预测肝脏炎症分级和纤维化分期的准确性.结果 体质量指数、年龄、性别、基因型和家族史对CHB患者肝脏炎症和纤维化无明显影响(P＜0.05).AST、ALT随着炎症、纤维化进展而升高,差异具有统计学意义(x2=71.193、96.344、47.847、63.981;P =0.000、0.000、0.000、0.000).纤维化为S4时,HBV DNA明显下降(x2=33.322,P=0.000).HBsAg水平随着炎症和纤维化程度加重而逐步下降(x2=68.173,15.719;P =0.000,0.000).HBsAg水平预测≤G3和≤S3的曲线下面积分别为0.732和0.793,特异度分别为0.778、0.891,灵敏度依次为0.685、0.633.结论 中国CHB患者HBsAg水平随着肝脏炎症分级和纤维化分期程度加重而逐渐下降.血清HBsAg水平对CHB患者肝脏炎症≤G3和纤维化≤S3的预测具有较高的特异性,且对纤维化的预测优于炎症.     

慢性HBV感染肝脏病理变化和生化ALT及病毒学关系

目的 探讨慢性HBV感染ALT、HBV DNA与肝脏病理的关系.方法 对81例慢性HBV感染患者检测血清ALT、HBV DNA.并进行肝活检病理检查.结果 肝脏炎症分级和纤维化分期与ALT明显相关(r值分别为0.683和0.419),与HBV DNA无相关性.随着肝脏炎症活动度和纤维化程度的加重,ALT有升高趋势(χ2趋势值分别为25.81和12.012),HBV DNA无升高趋势,而随着HBVDNA的升高,肝脏炎症活动度和纤维化程度并无加重趋势.肝组织HBsAg、HBcAg阳性组与阴性组的ALT、HBV DNA差异无统计学意义.结论 ALT与肝脏炎症活动度有明显相关性,仍是观察炎症变化的敏感指标,HBV DNA与肝组织炎症分级及纤维化分期无相关性.     

慢性乙型肝炎患者血清维生素E水平与肝组织病理的关系研究

目的 探讨慢性乙型肝炎(CHB)患者血清维生素E水平与肝组织病理的关系.方法 选择66例慢性乙型肝炎患者进行肝穿刺病理学检查,健康对照组10例.化学比色法检测血清维生素E表达水平,同时检测HBV DNA、HBeAg及肝功能.结果 与正常对照组相比,慢性乙型肝炎患者血清维生素E水平明显降低(P<0.01);HBeAg阳性组与HBeAg阴性组比较,血清维生素E水平无明显差别(P0.05).CHB患者血清维牛素E水平与肝脏组织炎症呈负相关关系(r=-0.451,P<0.05),而与肝脏组织纤维化程度无明显相关(r=0.02,P0.05).结论 维生素E作为体内重要的抗氧化剂,参与了慢性乙型肝炎的炎症过程.在肝脏炎症过程中,适当补充维生素E,可能有助于缓解病情.     

慢性乙型肝炎患者血清维生素E水平与肝组织病理的关系研究

目的 探讨慢性乙型肝炎(CHB)患者血清维生素E水平与肝组织病理的关系.方法 选择66例慢性乙型肝炎患者进行肝穿刺病理学检查,健康对照组10例.化学比色法检测血清维生素E表达水平,同时检测HBV DNA、HBeAg及肝功能.结果 与正常对照组相比,慢性乙型肝炎患者血清维生素E水平明显降低(P<0.01);HBeAg阳性组与HBeAg阴性组比较,血清维生素E水平无明显差别(P0.05).CHB患者血清维牛素E水平与肝脏组织炎症呈负相关关系(r=-0.451,P<0.05),而与肝脏组织纤维化程度无明显相关(r=0.02,P0.05).结论 维生素E作为体内重要的抗氧化剂,参与了慢性乙型肝炎的炎症过程.在肝脏炎症过程中,适当补充维生素E,可能有助于缓解病情.     

慢性乙型肝炎患者血清维生素E水平与肝组织病理的关系研究

目的 探讨慢性乙型肝炎(CHB)患者血清维生素E水平与肝组织病理的关系.方法 选择66例慢性乙型肝炎患者进行肝穿刺病理学检查,健康对照组10例.化学比色法检测血清维生素E表达水平,同时检测HBV DNA、HBeAg及肝功能.结果 与正常对照组相比,慢性乙型肝炎患者血清维生素E水平明显降低(P<0.01);HBeAg阳性组与HBeAg阴性组比较,血清维生素E水平无明显差别(P0.05).CHB患者血清维牛素E水平与肝脏组织炎症呈负相关关系(r=-0.451,P<0.05),而与肝脏组织纤维化程度无明显相关(r=0.02,P0.05).结论 维生素E作为体内重要的抗氧化剂,参与了慢性乙型肝炎的炎症过程.在肝脏炎症过程中,适当补充维生素E,可能有助于缓解病情.     

慢性乙型肝炎患者血清维生素E水平与肝组织病理的关系研究

目的 探讨慢性乙型肝炎(CHB)患者血清维生素E水平与肝组织病理的关系.方法 选择66例慢性乙型肝炎患者进行肝穿刺病理学检查,健康对照组10例.化学比色法检测血清维生素E表达水平,同时检测HBV DNA、HBeAg及肝功能.结果 与正常对照组相比,慢性乙型肝炎患者血清维生素E水平明显降低(P<0.01);HBeAg阳性组与HBeAg阴性组比较,血清维生素E水平无明显差别(P0.05).CHB患者血清维牛素E水平与肝脏组织炎症呈负相关关系(r=-0.451,P<0.05),而与肝脏组织纤维化程度无明显相关(r=0.02,P0.05).结论 维生素E作为体内重要的抗氧化剂,参与了慢性乙型肝炎的炎症过程.在肝脏炎症过程中,适当补充维生素E,可能有助于缓解病情.     

慢性乙型肝炎患者体内一氧化氮和一氧化氮合酶水平的研究

目的　探讨慢性乙型肝炎(慢乙肝)患者体内一氧化氮(NO)和一氧化氮合酶(NOS)水平及其意义。方法　检测37例慢乙肝患者NO、NOS[诱生型NOS(iNOS)和结构型NOS(cNOS) ]、肝功能、乙型肝炎病毒(HBV)DNA和HBV基因型(GT)并做出统计分析。结果　慢乙肝患者组与正常对照组比较,NO和iNOS的浓度均明显升高(P <0 0 5 ) ;丙氨酸转氨酶(ALT)异常组与正常对照组及ALT正常组比较:NO和iNOS的浓度均明显升高(P <0 0 5 ) ;ALT正常组与正常对照组比较:NO的浓度明显升高(P <0 0 5 ) ;cNOS在各组间比较差异无统计学意义。在慢乙肝患者中:NO和iNOS浓度与ALT水平呈明显正相关(r=0 36 7,r=0 4 74 )。NO和NOS与HBVDNA指标间均无明显相关关系。不同基因型组之间,NO和NOS的浓度差异无统计学意义(P >0 0 5 )。结论　在慢乙肝患者中,存在NO和iNOS水平升高的现象。慢乙肝患者ALT升高时,NO浓度高,对机体损伤重;慢乙肝患者ALT正常者,NO对机体无明显的损伤。NO和NOS与HBVDNA是相对独立的检测指标。NO水平与不同HBVGT患者病情及预后不同无明显关系。     

Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase

The inducible form of nitric oxide synthase (iNOS) is expressed in hepatic cells in pathological conditions. Its induction is involved in the development of liver fibrosis, and thus iNOS could be a therapeutic target for liver fibrosis. This review summarizes the role of iNOS in liver fibrosis, focusing on 1) iNOS biology, 2) iNOS-expressing liver cells, 3) iNOS-related therapeutic strategies, and 4) future directions.     

Determination of nitric oxide synthase activity and apoptosis of germ cells in different obstruction models

We aimed to determine the changes of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) immunoreactivity and apoptosis after proximal and distal obstruction models on ipsilateral and contralateral testicular tissues. Male albino Wistar rats were randomly divided into three groups (n=30): a control group which underwent sham operations (n=10), a unilateral vasal ligation (n=10) and a unilateral epididymal ligation group (n=10). iNOS and eNOS distribution and apoptosis were studied in both ipsilateral and contralateral testes using quantitative immunohistochemistry. Nitric oxide synthase activity was significantly affected in ipsilateral and contralateral testes cells after vasal and epididymal ligation. eNOS immunoreactivity increased markedly after ipsilateral vasal ligation (ILVL). Degeneration-related changes were also associated with changes in apoptotic rate. Analysis using the terminal dUTP nick end-labeling TUNEL method revealed that apoptotic cell numbers significantly increased after ILVL. p53 and bcl-2 immunoreactivity increased in both experimental groups compared with the sham-operated group. Changes in iNOS and eNOS immunolocalisation were strongly associated with cell damage, because germ cell degeneration was more prominent in the ILVL group. Altered p53 immunolocalisation was also associated with cell degeneration, and a rise in bcl-2 immunoreactivity might be considered to reflect a protective mechanism in the testis. These cellular changes could enlighten understanding of the interaction between testicular functioning and damage.     

参附注射液对肝脏缺血再灌注大鼠iNOS和NO水平的影响

目的探讨参附注射液(SF)对大鼠肝脏缺血再灌注损伤肝组织中诱导型一氧化氮合酶(iNOS)和血清一氧化氮(NO)的影响。方法32只Wistar大鼠随机分为参附实验组(SF组)和肝缺血再灌注组(IR组)。SF组腹腔注射参附注射液(10ml·kg-1),IR组大鼠给予相同剂量的生理盐水。两组均采用Pringle's法阻断肝门缺血15min再灌注1h、3h,测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)以及NO水平,并应用免疫组织化学法测定肝组织中iNOS表达。结果大鼠肝脏缺血15min再灌注1h和3h,SF组血清ALT、AST以及NO水平低于IR组(P<0.05),SF组肝组织iNOS阳性产物平均吸光度值、阳性面积百分率(%)明显低于IR组(P<0.05)。结论参附注射液抑制iNOS的表达,减少过量NO的生成,可能是其对肝脏缺血再灌注损伤的保护作用机制之一。     

Effect of inducible nitric oxide synthase on apoptosis in Candida-induced acute lung injury

Excessive nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) aggravates acute lung injury (ALI) by producing peroxinitrite. We previously showed that the expression of iNOS and lung injury were suppressed by inhalation of a novel iNOS inhibitor, ONO-1714, in mice with Candida-induced ALI, and that nitric oxide produced by iNOS and apoptosis of epithelial cells were found to have a crucial role in Candida-induced ALI. In the present study, we investigated the effect of NO on the apoptosis of alveolar epithelial cells in Candida-induced ALI. Mice were pretreated by inhalation of ONO-1714 or saline (vehicle control of ONO-1714), and were given an intravenous injection of Candida albicans to induce ALI. After 24 h from injection of Candida albicans, we performed bronchoalveolar lavage and removed lung tissues. We assessed apoptosis on the basis of TUNEL staining and caspase 3 activity. Our results showed that apoptosis was suppressed by inhibition of iNOS-derived NO production by ONO-1714 inhalation. The augmented production of NO increased FasL, TNF-alpha, and mRNA production of Bax of lung that induced apoptosis of alveolar epithelial cells. Inhibition of iNOS-derived NO production by ONO-1714 inhalation ameliorated Candida-induced ALI and improved survival by suppressing apoptosis of alveolar epithelial cells.     

Effects and Mechanism of Action of Inducible Nitric Oxide Synthase on Apoptosis in a Rat Model of Cerebral Ischemia‐Reperfusion Injury

Inducible nitric oxide synthase (iNOS) is a key enzyme in regulating nitric oxide (NO) synthesis under stress, and NO has varying ability to regulate apoptosis. The aim of this study was to investigate the effects and possible mechanism of action of iNOS on neuronal apoptosis in a rat model of cerebral focal ischemia and reperfusion injury in rats treated with S‐methylisothiourea sulfate (SMT), a high‐selective inhibitor of iNOS. Seventy‐two male Sprague‐Dawley (SD) rats were randomly divided into three groups: the sham, middle cerebral artery occlusion (MCAO) + vehicle, and MCAO + SMT groups. Neurobehavioral deficits, infarct zone size, and cortical neuron morphology were evaluated through the modified Garcia scores, 2,3,5‐triphenyltetrazolium chloride (TTC), and Nissl staining, respectively. Brain tissues and serum samples were collected at 72 hr post‐reperfusion for immunohistochemical analysis, Western blotting, Terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin Nick End Labeling assay (TUNEL) staining, and enzyme assays. The study found that inhibition of iNOS significantly attenuated the severity of the pathological changes observed as a result of ischemia‐reperfusion injury: SMT reduced NO content as well as total nitric oxide synthase (tNOS) and iNOS activities in both ischemic cerebral hemisphere and serum, improved neurobehavioral scores, reduced mortality, reduced the infarct volume ratio, attenuated morphological changes in cortical neurons, decreased the rate of apoptosis (TUNEL and caspase‐3‐positive), and increased phospho (p)‐AKT expression in ischemic penumbra. These results suggested that inhibition of iNOS might reduce the severity of ischemia‐reperfusion injury by inhibiting neuronal apoptosis via maintaining p‐AKT activity. Anat Rec, 299:246–255, 2016. © 2015 Wiley Periodicals, Inc.     

血清谷氨酰转肽酶含量测定在慢性乙型肝炎中的临床意义

目的探讨血清谷氨酰转肽酶（GGT）含量变化在慢性乙型肝炎（CHB）不同程度肝脏病理损害中的变化规律及临床意义。方法测定70例CHB患者血清ALT、AST、GGT水平，同时行肝活体组织检查，对肝脏进行炎症分级和纤维分期。分析ALT、AST、GGT与CHB之间的关系。结果（1）ALT、AST、GGT随炎症程度和纤维化程度的上升而上升，但到G4和s4后则下降。GGT随ALT、AST的升高而升高，ALT、AST和GGT的相关系数分别为：0．322、0．328（P〈0．05）。在保肝治疗后，ALT较快降至正常且GGT保持在一个较低水平的为轻度CHB，而随着ALT下降，GGT仍持续在一个较高水平的为中度及重度CHB，其中重度CHB的GGT水平有所波动。结论血清GGT比ALT、AST更准确的反映肝脏的炎症程度，GGT的活动度给临床判断慢乙肝的炎症提供了重要的判断依据。     

慢性乙肝病毒感染者肝脏病理与临床特征研究

目的 探讨肝活检病理组织学对慢性乙型肝炎病毒（HBV）携带者和血清ALT轻度升高慢性乙型肝炎患者（CHB）的临床意义.方法 105例慢性HBV感染患者全部进行肝组织活检,并按血清ALT水平分为3组：ALT≤0.5×正常参考值上限（ULN）为A组,0.5×ULN＜ALT≤1×ULN为B组,1×ULN＜ALT＜2×ULN为C组;对3组肝脏炎症程度及纤维化程度比较,并对不同肝组织炎症程度、纤维化程度与患者基本情况的关系进行分析.结果 105例患者中炎症程度≥G2者占40.95%,其中ALT正常的患者有30.43%≥G2;纤维化程度≥S2者占26.67%,其中ALT正常的患者中≥S2者占17.39%.血清ALT及透明质酸随肝脏炎症程度加重及纤维化分期的增加而增加（P＜O.05）.结论 密切随访血清ALT和透明质酸可协助了解肝脏病变情况,肝脏病理学依据仍然是决定是否抗病毒治疗的有力依据.     

Increased apoptosis in infiltrating mononuclear cells of colorectal cancer: a mechanism for tumor escape

CONTEXT: Disturbance in apoptosis has been proposed as one of the mechanisms involved in the immune response targeting tumor outgrowth. How colorectal cancer cells escape from attack by the immune system is not yet fully understood. OBJECTIVE: To investigate apoptotic molecules associated with colorectal cancer counterattack. DESIGN AND SETTING: Tissue samples of colon from 12 patients with colorectal cancer were collected and analyzed by immunostaining. In addition to tumorous tissues, corresponding nontumorous specimens of colon were obtained as controls. MAIN OUTCOME MEASURES: We examined the expression of Bcl-2, Bcl-xl, Bax, caspase-3, and inducible nitric oxide synthase in infiltrating mononuclear cells of colorectal cancer tissues and also in colorectal cancer tissues. The TUNEL assay was used to detect in situ apoptosis. RESULTS: Apoptosis was barely detectable in specimens of colorectal cancer, which was consistent with an increase in Bcl-2 level and a decrease in caspase-3 level. In contrast, infiltrating mononuclear cells of tumorous tissues showed a marked increase in apoptosis compared with those of nontumorous tissues. The increased apoptosis might have resulted from an imbalance of antiapoptotic and proapoptotic molecules, as reflected by reduction of Bcl-2 level and elevation of Bax level. The elevated caspase-3 levels found in this study could be a downstream effector of the Bcl-2 and Bax apoptotic pathways. A significant increase in inducible nitric oxide synthase observed in the infiltrating mononuclear cells might contribute to immunosuppression seen in colorectal cancer. CONCLUSION: It is tempting to speculate that aberrant expression of apoptotic molecules and inducible nitric oxide synthase in infiltrating mononuclear cells provides the underlying mechanism through which colorectal cancer cells escape attack by the immune system and subsequently grow without control.     

麻黄水提物对肺炎克雷伯菌所致重症肺炎幼龄大鼠细胞因子、间质纤维化以及NF-κB活化的影响

目的 探究麻黄水提物(ephedra water extract,EWE)对肺炎克雷伯菌所致重症肺炎幼龄大鼠细胞因子、 间质纤维化及NF-κB活化的影响.方法 采用肺炎克雷伯菌标准株菌液构建重症肺炎模型,EWE灌胃(100、200、400 mg/kg)治疗,10 d后检测各组幼鼠肺功能,以及外周血中炎性细胞因子白介素-...