肝脾舒对肝硬化大鼠内毒素血症的影响

目的探讨肝脾舒对肝硬化大鼠血浆内毒素是否有调节作用。方法雄性SD大鼠36只,随机分为正常组、模型组、肝脾舒组、杜秘克组,每组9只。正常组:每日腹腔注射生理盐水,模型组:采用40%CCl4橄榄油溶液腹腔注射制备肝硬化模型,肝脾舒组在此基础上每日给予肝脾舒灌胃,杜秘克组在模型组基础上每日给予杜秘克灌胃。取血检测血浆内毒素(LPS)水平。结果 3个月后模型组大鼠血浆内毒素水平较正常组升高(P<0.05);与模型组相比,肝脾舒组血清内毒素水平降低(P<0.05)。结论肝脾舒对肝硬化大鼠血浆内毒素水平有调节作用。     

双利肝配伍牛磺酸 精氨酸对四氯化碳急性肝损伤的作用及机制的研究

目的研究双利肝(丹参、大黄合剂)及其配伍牛磺酸、精氨酸对四氯化碳(CCl4)所致急性肝损伤的作用及机制。方法将实验动物随机分为4组:正常对照组、CCl4急性肝损伤组、双利肝治疗组、双利肝+精氨酸+牛磺酸治疗组,除正常对照组外,其余3组分别于实验第1天、第5天给予CCl4皮下注射,后两组分别给予双利肝、双利肝+精氨酸+牛磺酸合剂灌胃。于实验第8天处死动物,取血分别检测各组血浆内毒素(ET)、血清丙氨酸氨基转移酶(ALT)、γ-干扰素(IFN-γ)、白细胞介素-4(IL-4)、IL-2浓度。结果①CCl4急性肝损伤组与正常大鼠组相比,ET、ALT、IL-4水平明显增高(P<0.05或P<0.01),IL-2、IFN-γ水平明显降低(P<0.05)。②与CCl4急性肝损伤组相比,双利肝组ET、ALT、IL-4水平明显下降(P<0.05),IL-2、IFN-γ水平明显增高(P<0.05)。③双利肝+精氨酸+牛磺酸组的ET水平与CCl4急性肝损伤组相比明显降低(P<0.05),但效果不如单独双利肝组,而ALT水平下降却明显优于双利肝组。IL-4水平与双利肝组相比下降明显,IL-2、IFN-γ水平却有明显上升,但IFN-γ水平的变化差异无统计学意义。结论CCl4所致急性肝损伤大鼠存在肠源性内毒素血症(IETM),由此导致免疫功能紊乱,表现为Th1/Th2细胞失衡。经双利肝或双利肝伍用牛磺酸、精氨酸联合治疗,通过降低内毒素水平,调整Th1/Th2比例,从而增强细胞免疫功能,同时减轻肝损伤。由此提示对肝炎治疗若要取得满意疗效应采取综合治疗的对策。     

r-干扰素抗肝纤维化治疗57例

目的　 探讨r-干扰素的抗肝纤维化作用。 方法　 应用r -干扰素治疗慢性乙型肝炎及早期肝硬化 5 7例 ,每次 1MU ,肌肉注射 ,隔日 1次 ,疗程 6个月。治疗前后采用酶联免疫吸附检测血清透明质酸 (HA)、板层素 (LN)、Ⅲ型前胶原 (PCⅢ ) ,对其中 16例患者治疗前后肝穿刺活检、常规用苏木青 -伊红染色检测炎性分度、网状纤维染色测定肝纤维化的分级。 结果　 治疗后所有病例HA、LN、PCⅢ水平较治疗前有不同程度的下降 ;肝组织的纤维化程度改善。 结论　 应用r-干扰素治疗慢性乙肝可明显抑制肝纤维的生成与沉积 ,减轻肝纤维化。     

复方中药对肝星状细胞胶原合成与降解的影响

目的观察中药复方丹参对肝星状细胞胶原合成与降解的影响.方法选择肝星状细胞系作为体外研究对象,MTT法观察药物对细胞增殖的影响,ELISA法检测细胞上清液Ⅰ、Ⅲ、V型胶原含量,RNA-cDNA分子杂交检测细胞内Ⅰ、Ⅲ、Ⅳ型胶原及TGF β1 mRNA稳态水平.逆转录多聚酶链反应检测间质胶原酶及金属蛋白酶组织抑制因子-1基因表达水平.结果中药复方丹参明显抑制肝星状细胞增殖且呈剂量依赖趋势,与对照组比较,中药组细胞上清液中Ⅰ、Ⅲ、Ⅳ型胶原含量明显降低,细胞内Ⅰ、Ⅲ、Ⅳ型胶原及TGF β1 mRNA稳态水平明显降低,间质胶原酶基因表达水平明显增强,金属蛋白酶组织抑制因子-1基因表达水平明显受到抑制(P＜0.01).结论中药复方丹参可能通过抑制肝星状细胞的增殖,抑制胶原的异常合成,促进异常沉积胶原的降解,从而起到抗肝纤维化的作用.     

肝性脊髓病一例报告

患者,男,45岁,因反复腹胀1年伴意识障碍及双下肢无力2月于2003年10月23日入院。1年前患者因胆结石长期服用中药过程中出现乏力、腹胀．在贵州省人民医院作腹部B超发现“肝硬化腹水”,在继续服中药4个月后出现双手震颤、神志不清,贵州省人民医院诊断为“肝性脑病”,尔后,患者因大量食用高蛋白饮食而再次发生肝性脑病。近2     

肝硬化患者血一氧化氮、一氧化氮酶检测及其与内毒素的关系

目的　探讨肝硬化患者血一氧化氮 (NO)、一氧化氮酶 (NOS)的含量及其与内毒素的关系。方法　分别应用酶法和比色法测定 4 9例肝硬化患者血 NO、NOS及内毒素的含量 ,并与 35名正常人作对照。结果　肝硬化患者血 NO、NOS、内毒素水平均明显高于正常人组 (P<0 .0 5～ 0 .0 1)。结论　肝硬化患者血 NO NOS水平的增高与内毒素含量的增高有着密切的关系     

肝硬化患者血浆一氧化氮和内毒素水平及意义

目的观察肝硬化患者血浆一氧化氮 (NO)和内毒素的水平 ,并分析其相关性。方法测定 42例肝硬化患者及 2 7例正常人的血浆一氧化氮及内毒素水平。结果肝硬化组血浆NO及内毒素水平高于正常组 (P <0 0 5 ,0 0 1) ,且随肝功能Child -Pugh分级增加而升高 ;血浆NO水平与内毒素水平呈正相关 (r=0 712 ,P <0 0 1)。结论肝硬化时 ,NO合成增加与内毒素诱导有关 ,同时与肝硬化病情严重程度密切相关。     

双利肝和甘氨酸对重症急性胰腺炎大鼠疗效的观察

目的观察抗肠源性内毒素血症(IETM)药物双利肝(Slg)和甘氨酸(G1y)对重症急性胰腺炎(SAP)的治疗效果。方法选用Wistar大鼠80只,雌、雄不限,体重(260±20)g。由山西医科大学实验动物中心提供。随机分为SO组、SAP组、SAP+Slg组和SAP+Gly组,每组20只。观察48h各组血浆内毒素(ET)、血清淀粉酶(AMY)、胰腺病理评分和病死率。结果SO组大鼠血浆ET、血清AMY、病理评分最低,长期存活,SAP组各项指标最高,双利肝和甘氨酸治疗组各项指标与SAP组相比具有统计学意义。结论双利肝和甘氨酸皆能降低IETM的水平,减轻胰腺病理损害,使SAP大鼠病死率下降。     

复方鳖甲软肝片联合当飞利肝宁片治疗肝纤维化116例疗效评价

目的评价复方鳖甲软肝片联合当飞利肝宁片治疗肝纤维化的临床疗效。方法选择慢性肝炎肝纤维化代偿期患者232例,随机分为治疗组和对照组,各116例。两组患者均予以常规护肝治疗,治疗组加用复方鳖甲软肝片和当飞利肝宁片,对照组加用护肝片,疗程均为6个月。记录治疗后症状、体征、肝功能及血清透明质酸(HA)、Ⅲ型前胶原肽(PCⅢ)、甘氨胆酸(CG)、Ⅳ型胶原(ⅣC)、影像学改变等情况。结果与治疗前比较,治疗组HA,PCⅢ,CG,ⅣC水平均显著下降,与对照组比较,差异也有统计学意义(P<0.05)。结论复方鳖甲软肝片联合当飞利肝宁片能减轻患者症状、改善肝功能和肝纤维化,是治疗肝纤维化的有效药物。     

贺普丁联合复方鳖甲软肝片治疗乙型肝炎失代偿期肝硬化临床观察

目的 :观察乙型肝炎所致的失代偿期肝硬化应用贺普丁联合复方鳖甲软肝片的治疗效果。方法 :18例患者乙肝病毒 HBV DNA均阳性 ,其中 HBs Ag+抗 - HBc+HBe Ag阳性者 (大三阳 ) 14例 ,HBs Ag+抗 - HBc+HBe阳性者(小三阳 ) 4例 ,Child- pugh分级中 B级 13例 ,C级 5例 (贺普丁持续使用 1a,复方鳖甲软肝片从观察期起 3个月～ 9个月使用 ,共用 0 .5 a)。结果 :治疗 1a 17例患者 HBV DNA持续阴性 ,肝功能保持正常 ,Child- pugh分级下降≥ 2 ,1例患者治疗 9个月时 HBV DNA再次转阳 ,肝功能再次波动。结论 :贺普丁加复方鳖甲软肝片可改善失代偿期肝硬化患者的肝功能 ,抑制病毒复制 ,阻止或减轻肝纤维化 ,安全有效。     

川芎嗪治疗脑梗死的临床机制研究

目的:探讨川芎嗪治疗脑梗死的机制。方法:选取60名健康志愿者为A组,68例脑梗死患者为B组,测定其血浆中肿瘤坏死因子(TNF -α)、内皮素-1(ET -1)和一氧化氮(NO)含量,比较B组应用川芎嗪治疗前、后各项指标的变化,并与A组进行比较。结果:与A组比较,B组血浆TNF -α、ET -1含量显著升高,NO含量显著降低(P<0 05) ;经川芎嗪治疗后,B组血浆TNF -α、ET -1含量显著降低,NO含量显著升高(P<0. 05)。结论:川芎嗪可影响脑梗死患者血浆TNF -α、ET -1和NO的含量水平,并可能是其治疗脑梗死的主要作用机制。     

Endotoxin causes up-regulation of endothelin receptors in cultured hepatic stellate cells via nitric oxide-dependent and -independent mechanisms

Hepatic stellate cells (HSC) and their transformed phenotype found in the chronically injured liver play important roles in hepatic physiology and pathology. HSC produce and react to a potent contractile peptide endothelin-1 (ET-1) and also synthesize a vasorelaxant nitric oxide (NO) upon stimulation with endotoxin. However, whether endotoxin affects ET-1 system of HSC and if this is a mechanism of endotoxin-induced hepatic injury is not known. We characterized synthesis of ET-1 and NO and ET-1 receptors in cultured quiescent and transformed HSC subjected to endotoxin treatment. Endotoxin (1 - 1000 ng ml(-1)) stimulated synthesis of ET-1 and NO and up-regulated ET-1 receptors in both cell types. Inhibition of NO synthesis by N(G)-monomethyl-L-homoarginine strongly inhibited endotoxin-induced increase in ET-1 receptors in transformed HSC but produced small additional increase in quiescent HSC. Inhibition of soluble guanylyl cyclase by 1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one blocked the effect of endotoxin on ET-1 receptors in both cell types. Moreover, ET-1 receptors were increased in both cell types during earlier time points (1 - 4 h) of endotoxin treatment in the absence of the stimulation of NO synthesis. These results demonstrate that endotoxin up-regulates ET-1 receptors in HSC by NO-dependent and -independent mechanisms. Such effects of endotoxin can be of importance in acute endotoxemia and during chronic injury of the liver.     

p38 MAPK通路在TNF-α诱导人脐静脉内皮细胞分泌ET-1与eNOS中的作用及通心络干预影响

目的观察p38 MAPK信号通路在肿瘤坏死因子-α(TNF-α)诱导人脐静脉内皮细胞(HUVEC)表达内皮素-1(ET-1)与内皮型一氧化氮合酶(eNOS)中的作用及通心络干预影响。方法分别采用放免法及ELISA法测定不同浓度TNF-α(0、2.5、5、10、15、20μg·L-1)在不同时间点(0、1、2、4、8、12、24h)干预后HUVEC培养上清液中ET-1和eNOS含量;分别采用Western blot和Realtime RT-PCR方法检测TNF-α干预24h后HUVEC中ET-1、eNOS蛋白及mRNA表达;采用Western blot方法检测TNF-α干预10min、30min、60min后HUVEC磷酸化p38 MAPK蛋白表达。结果不同浓度TNF-α随时间延长均明显增加HUVEC培养上清液中ET-1含量,降低eNOS含量;TNF-α升高细胞中ET-1蛋白及mRNA水平、降低eNOS蛋白及mRNA水平、在各时间点均可升高细胞p-p38 MAPK蛋白表达。通心络可降低TNF-α诱导的HUVEC培养上清ET-1含量、降低细胞中ET-1蛋白及mRNA的异常升高;增加HUVEC培养上清中eNOS的表达、增加细胞中eNOS蛋白及mRNA的表达;明显抑制TNF-α诱导的细胞p-p38 MAPK表达。结论p38 MAPK信号通路参与了TNF-α诱导HUECV细胞分泌ET-1和eNOS,通心络对内皮细胞保护作用机制与抑制该通路有关。     

Effects of atorvastatin on fine particle-induced inflammatory response, oxidative stress and endothelial function in human umbilical vein endothelial cells

The study is to explore the toxicity of organic extracts and water-soluble fraction of fine particles on human umbilical vein endothelial cells (HUVECs). The exposure doses were 100, 200 and 400 μg/ml, respectively, for two kinds of fractions. Moreover, atorvastatin was used for intervention study. HUVECs were stimulated by 400 μg/ml organic and water soluble extracts, respectively, immediately followed by treatment with atorvastatin in concentrations of 0.1 μmol/L, 1 μmol/L and 10 μmol/L, respectively. Cell viability, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), reactive oxygen species (ROS) and the expression of interleukin-6 beta (IL-6), tumor necrosis factor-α (TNF-α), endothelin-1 and P-selectin were determined in cells. The results showed that MDA and ROS increased in HUVECs after exposed to organic extracts and water-soluble fraction, whereas cell viability, NO and SOD decreased. The mRNA expression of IL-6, TNF-α, endothelin-1 (ET-1) and P-selectin increased after exposed to different fractions. Meanwhile, at the same exposure dose, water-soluble fraction caused more significant increase of MDA, IL-6, TNF-α and P-selectin and decrease of cell viability and NO when compared to organic extracts. Compared to no atorvastatin group, the levels of MDA, ROS and the expression of IL-6, TNF-α, ET-1 and P-selectin decreased in HUVECs in adding atorvastatin group, but cell viability, NO and SOD increased, which indicated that atorvastatin attenuated fine particle-induced inflammatory response, oxidative stress and endothelial damage. The results hinted that the inflammatory response, oxidative stress and endothelial dysfunction might be the mechanisms of cardiovascular injury induced by different fractions of ambient fine particles.     

Antifibrotic effect of meloxicam in rat liver: role of nuclear factor kappa B,proinflammatory cytokines,and oxidative stress

This study was aimed at investigating the antifibrotic effect of meloxicam in CCl4-induced liver fibrosis and elucidating its underlying mechanism. Forty male rats were equally randomized for 8-week treatment with corn oil (negative control), CCl4 (to induce liver fibrosis), and/or meloxicam. Meloxicam effectively ameliorated the CCl4-induced alterations in liver histology, liver weight to body weight ratio, liver functions, and serum markers for liver fibrosis (hyaluronic acid, laminin, and PCIII). Meloxicam significantly abrogated CCl4-induced elevation of messenger RNA (mRNA) expressions for collagen I and alpha smooth muscle actin (α-SMA) and hepatic contents of hydroxyproline, transforming growth factor beta (TGF-β), and tissue inhibitor of matrix metalloproteases (TIMP-1). Meloxicam mitigated CCl4-induced elevation in hepatic levels of nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), total nitric oxide (NO), interleukin-l beta (IL 1β), and prostaglandin E2 (PGE2). Meloxicam modulated CCl4-induced disturbance of liver cytochrome P450 subfamily 2E1 (CYP2E1) and glutathione-S-transferase (GST). The attenuation of meloxicam to liver fibrosis was associated with suppression of oxidative stress via reduction of lipid peroxides along with induction of reduced glutathione content and enhancement of superoxide dismutase, glutathione peroxidase, and catalase activities. This study provides an evidence for antifibrotic effect of meloxicam against CCl4-induced liver fibrosis in rat. The antifibrotic mechanism of meloxicam could be through decreasing NF-κB level and subsequent proinflammatory cytokine production (TNF-α, NO, IL-1 beta, and PGE2) and, hence, collagen deposition through inhibition of TIMP-1 and TGF-β. Abrogation of oxidative stress and modulation of liver-metabolizing enzymes (CYP2E1 and GST) were also involved.     

肺动脉高压与脑利钠肽、血管内皮功能和炎性细胞因子的相关性

摘 要：目的 通过观察肺动脉高压（PAH）患者的肺动脉收缩压（PASP）与脑利钠肽（BNP）、血管内皮功能和炎性细胞因子的相关性,进一步探讨PAH发病机制。方法 测定92例PAH患者和50例健康者的肺动脉收缩压（PASP）、血浆BNP、内皮素-1（ET-1）、血清一氧化氮（NO）、超敏C反应蛋白（hs-CRP）和肿瘤坏死因子-α（TNF-α）等指标。结果 PAH患者的血浆BNP、ET-1、血清hs-CRP和TNF-α显著高于对照组（P<0.05）,血清NO显著低于对照组（P<0.05）。PAH患者的PASP与血浆BNP（r=0.574）、hs-CRP（r=0.423）、ET-1（r=0.402）和TNF-α（r=0.366）呈显著正相关;与血清NO水平呈显著负相关（r=-0.378）。结论 PAH的发生发展过程是BNP、内皮系统和炎性反应等多因素综合作用的结果。     

Ascorbic acid suppresses endotoxemia and NF-κB signaling cascade in alcoholic liver fibrosis in guinea pigs: A mechanistic approach

Alcohol consumption increases the small intestinal bacterial overgrowth (SIBO) and intestinal permeability of endotoxin. The endotoxin mediated inflammatory signaling plays a major role in alcoholic liver fibrosis. We evaluated the effect of ascorbic acid (AA), silymarin and alcohol abstention on the alcohol induced endotoxemia and NF-κB activation cascade pathway in guinea pigs (Cavia porcellus). Guinea pigs were administered ethanol at a daily dose of 4 g/kg b.wt for 90 days. After 90 days, ethanol administration was stopped. The ethanol treated animals were divided into abstention, silymarin (250 mg/kg b.wt) and AA (250 mg/kg b.wt) supplemented groups and maintained for 30 days. The SIBO, intestinal permeability and endotoxin were significantly increased in the ethanol group. The mRNA expressions of intestinal proteins claudin, occludin and zona occludens-1 were significantly decreased in ethanol group. The mRNA levels of inflammatory receptors, activity of IKKβ and the protein expressions of phospho-IκBα, NF-κB, TNF-α, TGF-β₁ and IL-6 were also altered in ethanol group. The expressions of fibrosis markers α-SMA, α₁ (I) collagen and sirius red staining in the liver revealed the induction of fibrosis. But the supplementation of AA could induce greater reduction of ethanol induced SIBO, intestinal barrier defects, NF-κB activation and liver fibrosis than silymarin. The possible mechanism may be the inhibitory effect of AA on SIBO, intestinal barrier defect and IKKβ, which decreased the activation of NF-κB and synthesis of cytokines. This might have led to suppression of HSCs activation and liver fibrosis.     

Escin attenuates acute lung injury induced by endotoxin in mice

Endotoxin causes multiple organ dysfunctions, including acute lung injury (ALI). The current therapeutic strategies for endotoxemia are designed to neutralize one or more of the inflammatory mediators. Accumulating experimental evidence suggests that escin exerts anti-inflammatory and antiedematous effects. The aim of this study was to evaluate the effect of escin on ALI induced by endotoxin in mice. ALI was induced by injection of lipopolysaccharide (LPS) intravenously. The mice were given dexamethasone or escin before injection of LPS. The mortality rate was recorded. Tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO) were measured. Pulmonary superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, glutathione (GSH), malondialdehyde (MDA) contents, and myeloperoxidase (MPO) activity were also determined. The expression of glucocorticoid receptor (GR) level was detected by Western blotting. Pretreatment with escin could decrease the mortality rate, attenuate lung injury resulted from LPS, down-regulate the level of the inflammation mediators, including NO, TNF-α, and IL-1β, enhance the endogenous antioxidant capacity, and up-regulating the GR expression in lung. The results suggest that escin may have potent protective effect on the LPS-induced ALI by inhibiting of the inflammatory response, and its mechanism involves in up-regulating the GR and enhancing the endogenous antioxidant capacity.     

Beta-谷甾醇通过抑制TNF-α-NF-κB和TβR1-Smad2/3信号通路抗小鼠肝纤维化损伤

目的探讨Beta-谷甾醇对四氯化碳(carbon tetrachloride,CCL 4)诱导的小鼠肝纤维的作用与机制。方法50只C57BL/6♂小鼠随机分成5组:正常组、CCL 4组、Beta-谷甾醇低中高剂量组(BS-L/M/H),每组10只。腹腔注射CCL 4制肝纤维化模型,共30 d,于前15 d灌胃不同剂量Beta-谷甾醇。处死后,观察大体形态,测量肝指数,HE和Masson染色观察肝组织和胶原纤维,Elisa测血清(ALT)、(AST)变化,免疫组化和Western blot检测α-SMA、CollagenⅠ的表达,Elisa和Western blot检测信号通路TNF-α-NF-κB和TβR1-Smad2/3的变化。结果与正常组比,BS各组显著性地抑制了CCL 4引起的肝指数、ALT、AST、α-SMA、collagenⅠ的增高,该作用呈量效依赖性(P<0.05或P<0.01),BS各组肝形态、炎症细胞浸润与胶原纤维变化也呈剂量依赖性优于模型组,同时,BS-M降低了信号通路中TβR1、Smad2/3、TNF-α和p-NF-κB因子的表达(P<0.05)。结论Beta-谷甾醇呈剂量依赖抑制CCL 4诱导的小鼠肝纤维化,且其作用机制与抑制TNF-α-NF-κB和TβR1-Smad2/3信号通路相关。