人工肝支持系统治疗慢性重型肝炎34例临床研究

目的　研究人工肝支持系统血浆置换疗法治疗慢性重型肝炎的临床疗效 ,探讨血浆内毒素、转化生长因子 β1(TGF β1)、一氧化氮 (NO)、肝细胞生长因子 (HGF)在慢性重型肝炎发病机制中的作用。方法　将 5 9例慢性重型肝炎患者随机分为治疗组与对照组。两组入院后均给予内科综合治疗 ,治疗组 34例加用人工肝支持系统血浆置换治疗。观察治疗前后肝功能、血浆内毒素、TGF β1、NO、HGF水平变化。结果　治疗组治疗后肝功能明显改善 ,生存率较对照组提高 (P <0 0 5 ) ;血浆内毒素、TGF β1、NO水平较对照组明显下降 (P <0 0 5、P <0 0 1、P <0 0 1) ;血浆HGF水平上升较对照组明显 (P <0 0 1)。结论　人工肝支持系统血浆置换疗法能有效清除血浆内毒素、TGF β1、NO毒性物质和肝细胞再生抑制因子 ,提高血浆HGF含量 ,减轻肝细胞炎症、促进肝细胞再生 ,提高慢性重型肝炎生存率。     

TGF-β1、TNF-α mRNA在肝包虫囊肿周围人体纤维囊壁中的特异性分层表达

目的探讨TGF鄄β1、TNF鄄αmRNA在形成肝包虫囊肿周围人体纤维囊壁中的作用及其临床意义。方法采用原位杂交方法检测转化生长因子鄄β1(TGF鄄β1)及肿瘤坏死因子鄄α(TNF鄄α)的mRNA在40例肝包虫囊肿周围纤维囊壁中表达。结果TGF鄄β1、TNF鄄α在肝包虫囊肿周围纤维囊壁中出现特异性分层表达。靠近虫体侧纤维囊壁中,TGF鄄β1、TNF鄄α的阳性细胞表达率分别为(10.24±2.90)%、(16.22±2.84)%。靠近肝实质侧纤维囊壁中,TGF鄄β1、TNF鄄α的阳性细胞表达率分别为(37.51±7.45)%、(25.76±5.05)%。TGF鄄β1、TNF鄄α在2层中表达的差异均有显著意义(P<0.01)。靠近肝实质侧纤维囊壁中TGF鄄β1与TNF鄄α之间表达的差异也有显著意义(P<0.05)。结论肝包虫囊肿周围人体纤维囊壁分层,TGF鄄β1、TNF鄄α与肝实质侧纤维囊壁的形成有密切关系。     

人工肝支持系统治疗对重型肝炎患者血清TNF-α、IL-2、IL-10和IL-15水平的影响

目的 探讨重型肝炎患者人工肝支持系统(ALSS)治疗前后外周血中肿瘤坏死因子-α(TNF-α)、白细胞介素-2(IL-2)、白细胞介素-10(IL-10)、白细胞介素-15(IL-15)水平的变化。方法 应用血浆置换技术治疗重型肝炎患者59例，采用ELISA法于每次治疗前后检测TNF-α、IL-2、IL-10、IL-15水平，并观察其动态变化。结果 重型肝炎患者血清TNF-α水平明显高于对照组，IL-2水平明显低于对照组，ALSS治疗后TNF-α水平明显下降，而IL-2、IL-l0则呈上升趋势，治疗前后IL-15水平无明显变化。结论 ALSS治疗能降低重型肝炎患者TNF-α含量，并升高IN-2和IL-10水平，从而抑制炎性介质的产生，减轻免疫反应对肝细胞的损伤，提高重型肝炎的存活率。     

血浆置换治疗慢性重型肝炎

目的：探讨血浆置换治疗慢性重肝炎的疗效机制。方法：将25例慢性重型肝炎患者分为治疗组与对照组，对照组入院后给予内科综合治疗，治疗组在内科综合治疗的基础上加血浆置换治疗。检测两组治疗前后的血氨、血浆内毒素、肿瘤坏死因子α（TNF－α）、转化生长因子β1（TGF－β1）、肝细胞生长因子（HGF）、血清氨基酸水平的变化。结果：治疗组血氨、血浆内毒素、TNF－α、TGF－β1治疗前后下降幅度较对照组明显（P＜0．05），而HGF浓度呈上升趋势；治疗组甲硫氨酸浓度下降较对照组明显（P＜0．05），其他氨基酸差异无显著性（P＞0．05），支链氨基酸与芳香族氨基酸比值无明显上升。结论：血浆置换可降低血氨、内毒素、TNF－α、甲硫氨酸等有害物质，抑制TGF－β1上升，而HGF上升，缓解炎症，抑制肝脏纤维化、促进肝细胞再生，为患者的自然恢复争取机会。     

人工肝支持系统治疗重型肝炎36例临床疗效分析

目的　研究人工肝支持系统 (ALSS)治疗重型肝炎的临床疗效。方法　对 3 6例重型肝炎患者在内科综合治疗基础上 ,应用人工肝支持系统 (ALSS)进行治疗 ,并检测治疗前后肝功能、胆碱酯酶 (CHE)、凝血酶原活动度 (PTA)、内毒素 (ET)及细胞因子的变化 ,观察治疗相关的不良反应及患者耐受情况 ,比较重型肝炎不同期应用人工肝支持系统的疗效。结果　治疗后患者乏力、腹胀、纳差等症状及肝功能明显改善 ,CHE、PTA显著上升 (P <0 .0 1) ;ET、TNF α、IL 8和sIL 2R明显降低 ,IL 10显著升高 ,IL 2水平无变化。重型肝炎早、中、晚期应用工肝支持系统治疗 ,存活率分别为85 .6%、70 %和 10 % ,人工肝治疗组总体存活率为 5 2 .8% ,显著高于对照组 ( 3 3 .3 % ) ,P <0 .0 1。结论　人工肝支持系统是治疗重型肝炎的有效手段 ,早、中期治疗可取得满意疗效     

肝组织与血清转化生长因子β1表达水平与病毒性肝炎患者肝纤维化的关系

目的 观察肝纤维化不同阶段转化生长因子β_1(TGF β_1)在肝组织内表达情况及血清水平,探讨TGF β_1与肝纤维化发生发展的关系,评价肝脏、血清TGF β_1及血清Ⅲ型胶原(PC Ⅲ)、透明质酸(HA)、层黏连蛋白(LN)、Ⅳ型胶原(C Ⅳ)反映肝纤维化情况。 方法 随机选取92例慢性病毒性肝炎患者,酶联免疫法检测TGF β_1血清水平,其中31例行肝组织活检,做TGF β_1的免疫组织化学染色和胶原纤维染色,并用多媒体彩色图文分析系统对肝脏TGF β_1和胶原进行图像分析定量。 结果 (1)按肝组织纤维化程度(S)分组,除S_2组与S_1组比较外,TGF β_1随纤维化分期加重而表达增加,F=13.46,P<0.05。按炎症活动度级别(G)分组,G_1组、G_2组、G_3组、G_4组之间两两比较差异无显著性。(2)肝组织TGF β_1水平与血清TGF β_1浓度呈正相关(r=0.896)。肝组织TGF β_1水平与肝组织胶原含量呈正相关(r=0.863),肝组织TGF β_1水平与血清PC Ⅲ、HA、LN、C Ⅳ之间均呈正相关,r分别为0.824、0.720、0.747、0.839。 结论 肝脏和血清TGFβ_1表达水平与肝组织纤维化程度密切相关,且较HA、LN、C Ⅳ三项常规指标在反映早期纤维化方面更敏感。     

血小板活化因子在病毒性肝炎中的变化及意义

目的　探讨血小板活化因子 (PAF)、血清肿瘤坏死因子α(TNF α)、丙二醛 (MDA)和血浆内毒素 (ET)等指标在病毒性肝炎中的变化和意义。方法　分别采用反相高效液相色谱测定法(rHPLC)和生物学法、双抗体夹心酶联免疫吸附试验 (ELISA)、鲎试验 (LLT)、硫化巴比妥酸法 (TBA)对 6 0例健康对照者、2 1例急性肝炎、85例慢性肝炎、2 6例重型肝炎患者进行血PAF、TNF α、ET和MDA等指标的测定、分析。结果　rHPLC法与生物学法比较 ,两者呈较好的相关性 (r =0 .912 )。肝炎患者血PAF、TNF α、内毒素和MDA值均明显高于正常对照组 (P <0 .0 1)。重型肝炎患者血中PAF水平与ET、TNF α水平呈显著正相关 (r =0 .892 ,P <0 .0 1;r =0 .76 7,P <0 .0 1) ;血清TNF α水平与内毒素水平成正相关 (r =0 .86 3,P <0 .0 1)。结论　rHPLC法测定PAF可靠 ,能正确地反映血中PAF水平 ;联合测定血PAF、MDA、ET、TNF α有助于检测病毒性肝炎的进行性损害程度及预后判断 ,有助于推动病毒性肝炎的基础与临床研究。     

慢性乙型肝炎患者血清中TGF—β1及TNF—α含量与肝纤维化程度的关系探讨

目的：观察分析慢性乙型肝炎患者血清中TGF－β1、TNF－α的含量与肝纤维化程度的关系,寻求肝纤维化的诊断.工从细胞因子角度探讨肝纤维化的发病机理。方法：采用酶联免疫吸附试验法（ELISA）和放射免疫分析法（RIA）分别测定30例正常人员、45例慢性乙型肝炎及10例肝硬化患者血清中TGF－β1和TNF－α的含量。结果：①慢性乙型肝炎轻、中、重复度及肝硬化患者血清TGF－β1、TNF－α水平均不同程度高于对照组（P＜0．01或P＜0．05）,并且随着肝损害程度的加重逐渐升高,与肝损害程度呈正相关关系（P＜0．01）②血清中TGF－β1、TNF－α水平与肝纤维化程度呈正相关关系（P＜0．01）。结论：①血清TGF－β1、TNF－α水平随着肝纤维化程度加重而升高,与肝纤维经发展发展密相关。②对血清中TGF－β1、TNF－α水平同时测定,可作为诊断肝纤维化的血清学指标。③寻找有效的方法拮抗TGF－β1、TNF－α对抗纤维2经治疗具有重要意义。     

人工肝支持系统治疗重型肝炎患者血清IL-6、IL-12和TNF-α水平变化

目的　观察重型肝炎患者经血浆置换(PE)治疗前后血清IL 6、IL 12、TNF α水平变化。方法　使用血浆置换技术治疗重型肝炎74例,采用ELISA法检测IL 6、IL 12、TNF α。结果　PE治疗后IL 6、TNF α与治疗前比较明显降低,IL 12较治疗前明显升高(P <0 .0 1)。本组重型肝炎的成活率为66.2 %。结论　PE治疗后能降低血清IL 6、TNF α水平,提高IL 12水平,减轻重型肝炎时肝细胞的损伤,提高重型肝炎的存活率。     

反义转化生长因子βⅡ型受体表达质粒对实验性肝纤维化的影响

目的 观察反义转化生长因子βⅡ型受作(TGF βRⅡ)表达质粒对实验性肝纤维化的影响。方法 运用重组DNA技术中构建反义TGF βRⅡ真核细胞表达质粒,采用猪血清腹腔注射制备免疫性大鼠肝纤维化模型,实验动物分为肝纤维化模型组、反义TGF βRⅡ治疗组、pCDNA3对照组及正常对照组。反义TGF βRⅡ质粒和pCDNA3空质粒与糖化多聚赖氨酸偶联后经尾静脉分别导入大鼠体内,通过northern blot、RT-PCR、Western blot检测外源导入质粒在肝组织中的表达,检测血清转化生长因子β1(TGFβ1)、肝组织羟脯氨酸测定,Ⅰ、Ⅲ型胶原免疫组织化学与Van Gieson染色观察反义TGF βRⅡ质粒对大鼠肝纤维化的影响。 结果 反义TGF βRⅡ表达质粒可在肝组织中获得确切表达,其表达可使反义治疗组血清TGF β1含量下降,反义TGF βRⅡ治疗组为(23.16 ± 3.13)ng/ml,模型组为(32.96±3.79)ng/ml,F=36.73,P<0.01。肝组织羟脯氦酸含量下降,治疗组为(0.17±0.01)mg/g,模型组为(0.30±0.03)mg/g,F=15.48,P<0.01。减少了肝组织Ⅰ、Ⅲ型胶原的沉积,治疗组Ⅰ型胶原为650.26±51.51,Ⅲ型胶原为661.5 8±55.28,模型组Ⅰ型胶原为1209.44±16.60,Ⅲ型胶原为1175.14±121.44,F值分圳为69.87、70.46,P<0.01。并促进反义治疗组肝脏病理形态一定程度的改善。     

人工肝支持系统治疗重型肝炎应用研究

目的　为进一步探索人工肝支持系统（ＡＬＳＳ） 治疗重型肝炎临床应用疗效,并研究其机制。方法　对８８ 例重型肝炎患者应用ＡＬＳＳ 治疗,并检测治疗前、后肝功能,内毒素含量等,并对部分患者检测血清乙型肝炎病毒（ＨＢＶ） 含量、氨基酸谱等。比较重型肝炎不同期应用ＡＬＳＳ治疗效果。结果　ＡＬＳＳ治疗后,重型肝炎患者肝功能明显改善,血内毒素由治疗前（６２ ．４１ ±２８ ．１８）ｎｇ／Ｌ降至治疗后（４３ ．５６ ±２２ ．１５）ｎｇ／Ｌ（ Ｐ＜ ０ ．００１） ,ＨＢＶ 量由（２ ５８８ ±１ ５３４）ｃｏｐｉｅｓ／ｍｌ 降至（１ ８１５ ±６２０）ｃｏｐｉｅｓ／ｍｌ（ Ｐ＜ ０ ．０５） 。蛋氨酸和芳香族氨基酸浓度下降,ＢＣＡＡ／ＡＡＡ 比值由１ ．１８ 上升至１ ．５２（ Ｐ＜ ０ ．０５） 。早、中、晚期重型肝炎应用ＡＬＳＳ治疗治愈好转率分别为９０ ．９ ％ 、７１ ．０ ％ 、２０ ．５ ％ 。结论　ＡＬＳＳ治疗重型肝炎疗效可靠,在早、中期治疗最为适宜。     

慢性肝病患者肠道通透性和炎症因子变化的研究

目的 探讨慢性肝病患者肠黏膜屏障及炎症细胞因子的变化.方法 收集各种慢性肝病患者和正常人的血清,统一采用酶联免疫吸附法和改良分光光度法检测血清D-乳酸(D-Lac)、二胺氧化酶(DAO)、内毒素(ET)、降钙素原(PCT)和肿瘤坏死因子(TNF)水平.结果 各组患者人口学特征无明显差别(P>0.05),从肝炎病毒携带者...     

High-density lipoproteins reduce the effect of endotoxin on cytokine production and systemic hemodynamics in cirrhotic rats with ascites

BACKGROUND/AIMS: Hypersensitivity to endotoxin is a recognized feature in cirrhosis. High-density lipoproteins (HDL) have a high capacity to inactivate endotoxin. The aim was to determine if HDL reduces the effect of endotoxin on cytokine production and systemic hemodynamics in experimental cirrhosis. METHODS: The study was performed in control and rats with carbon-tetrachloride induced cirrhosis with ascites. Hemodynamic parameters were determined before and after several doses of endotoxin. The effects of 25 microg/kg of endotoxin on the serum concentration of TNFalpha and mean arterial pressure (MAP) were determined after treatment with HDL (80 mg/kg) or saline. RESULTS: Whereas endotoxin decreased MAP only at doses of 100 and 1000 microg/kg in control rats, in cirrhotic rats significant hypotension occurred at doses of 25, 50, 100 and 1000 microg/kg. Following the administration of endotoxin (25 microg/kg) the serum levels of TNFalpha were 140 times higher in cirrhotic than in control rats (89?835+/-21?090 vs. 625+/-137 pg/ml; P<0.001). Serum TNFalpha was 80% lower in cirrhotic rats pretreated with HDL (18?890+/-5012 pg/ml; P<0.001) than in those pretreated with saline. The administration of endotoxin (25 microg/kg) was associated with a significant lower decrease of MAP in cirrhotic rats pretreated with HDL than in those receiving saline (11.9+/-3.5 vs. 24.7+/-4.3%; P<0.05). CONCLUSIONS: HDL attenuates the increased effect of endotoxin on cytokine production and systemic hemodynamic in cirrhosis.     

Low secretion of tumor necrosis factor alpha, but no other Th1 or Th2 cytokines, by peripheral blood mononuclear cells correlates with chronicity in reactive arthritis.

OBJECTIVE: To determine Th1 and Th2 cytokine production in patients with reactive arthritis (ReA) in relation to disease outcome and in comparison with rheumatoid arthritis (RA). METHODS: Secretion of tumor necrosis factor alpha (TNFalpha), interferon-gamma, interleukin-10 (IL-10), and IL-4 by peripheral blood mononuclear cells (PBMC) from 53 patients with early ReA (disease duration <8 weeks, 64% HLA-B27 positive) and 30 patients with early, untreated RA (disease duration <6 months) was determined by enzyme-linked immunosorbent assay (ELISA) after ex vivo stimulation. Intracellular cytokine staining with quantification of positive T cells by fluorescence-activated cell sorting (FACS) was performed in 12 ReA patients and 12 RA patients. In 27 ReA patients, cytokine secretion was measured again after 3 months. Patients were followed up for 1 year, and cytokine patterns were correlated with disease duration. RESULTS: TNFalpha secreted by whole PBMC and by T cells was significantly lower, by ELISA and by FACS, in ReA patients than in RA patients, while no significant differences were detected for the other cytokines. ReA patients with a disease duration of > or =6 months showed significantly lower TNFalpha secretion than patients with a disease duration of <6 months (mean +/- SD 385 +/- 207 pg/ml versus 684 +/- 277 pg/ml; P = 0.003). Furthermore, low TNFalpha secretion after 3 months also correlated significantly with a more chronic course of disease. HLA-B27 positive patients secreted less TNFalpha than did those who were B27 negative (338 +/- 214 pg/ml versus 512 +/- 207 pg/ml; P = 0.05), and patients with a more chronic course had a higher frequency of B27 positivity (47% versus 80%; P = 0.01). Among the 27 HLA-B27 positive patients, TNFalpha secretion in those with a disease duration of > or = 6 months was lower than that in the 7 with a disease duration of <6 months (308 +/- 167 pg/ml versus 562 +/- 308 pg/ml; P = 0.04). CONCLUSION: Low TNFalpha secretion and HLA-B27 status correlate with longer disease duration in ReA patients, possibly with an additive effect. The diminished TNFalpha production might reflect a state of relative immunodeficiency contributing to bacterial persistence in ReA.     

Protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis

AIM: To investigate the protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis (SAP). METHODS: One hundred and eighty SD rats were randomly assigned to the model group, Baicalin-treated group, octreotide-treated group and sham operation group. The mortality, plasma endotoxin level, contents of blood urea nitrogen (BUN), creatinine (CREA), phospholipase A2 (PLA2), nitrogen monoxide (NO), tumor necrosis factor (TNF)-alpha, IL-6 and endothelin-1 (ET-1) in serum, expression levels of renal Bax and Bcl-2 protein, apoptotic indexes and pathological changes of kidney were observed at 3, 6 and 12 h after operation. RESULTS: The renal pathological changes were milder in treated group than in model group. The survival at 12 h and renal apoptotic indexes at 6 h were significantly (P<0.05) higher in treated group than in model group [66.67% vs 100%; 0.00 (0.02)% and 0.00 (0.04)% vs 0.00 (0.00)%, respectively]. The serum CREA content was markedly lower in octreotide-treated group than in model group at 3 h and 6 h (P<0.01, 29.200+/-5.710 micromol/L vs 38.400+/-11.344 micromol/L; P<0.05, 33.533+/-10.106 micromol/L vs 45.154+/-17.435 micromol/L, respectively). The expression level of renal Bax protein was not significantly different between model group and treated groups at all time points. The expression level of renal Bcl-2 protein was lower in Baicalin-treated group than in model group at 6 h [P<0.001, 0.00 (0.00) grade score vs 3.00 (3.00) grade score]. The Bcl-2 expression level was lower in octreotide-treated group than in model group at 6 h and 12 h [P<0.05, 0.00 (0.00) grade score vs 3.00 (3.00) grade score; 0.00 (0.00) grade score vs 0.00 (1.25) grade score, respectively]. The serum NO contents were lower in treated groups than in model group at 3 h and 12 h [P<0.05, 57.50 (22.50) and 52.50 (15.00) micromol/L vs 65.00 (7.50) micromol/L; P<0.01, 57.50 (27.50) and 45.00 (12.50) micromol/L vs 74.10 (26.15) micromol/L, respectively]. The plasma endotoxin content and serum BUN content (at 6 h and 12 h) were lower in treated groups than in model group. The contents of IL-6, ET-1, TNF-alpha (at 6 h) and PLA2 (at 6 h and 12 h) were lower in treated groups than in model group [P<0.001, 3.031 (0.870) and 2.646 (1.373) pg/mL vs 5.437 (1.025) pg/mL; 2.882 (1.392) and 3.076 (1.205) pg/mL vs 6.817 (0.810) pg/mL; 2.832 (0.597) and 2.462 (1.353) pg/mL vs 5.356 (0.747) pg/mL; 16.226 (3.174) and 14.855 (5.747) pg/mL vs 25.625 (7.973) pg/mL; 18.625 (5.780) and 15.185 (1.761) pg/mL vs 24.725 (3.759) pg/mL; 65.10 (27.51) and 47.60 (16.50) pg/mL vs 92.15 (23.12) pg/mL; 67.91+/-20.61 and 66.86+/-22.10 U/mL, 63.13+/-26.31 and 53.63+/-12.28 U/mL vs 101.46+/-14.67 and 105.33+/-18.10 U/mL, respectively]. CONCLUSION: Both Baicalin and octreotide can protect the kidney of rats with severe acute pancreatitis. The therapeutic mechanisms of Baicalin and octreotide might be related to their inhibition of inflammatory mediators and induction of apoptosis. Baicalin might be a promising therapeutic tool for severe acute pancreatitis.     

Inflammatory cytokines and the possible immunological role for lipoproteins in chronic heart failure

AIMS: We studied the clinical and immunological importance of fasting cholesterol, HDL, LDL and triglycerides in patients with chronic heart failure in relation to plasma concentrations of tumor necrosis factor-alpha (TNFalpha), soluble TNF receptor-1 and -2 (sTNF-R1 and -R2), and a ratio potentially indicating recent endotoxin bioactivity (soluble [s] CD14/total cholesterol). METHODS AND RESULTS: Fifty-eight stable, non-oedematous patients with established heart failure and 19 controls were studied prospectively. Concentrations of sTNF-R1 and sCD14 were higher in patients than in controls (1238+/-96 vs. 632+/-72 pg/ml, P=0.005 and 3401+/-120 vs. 2775+/-139 pg/ml, P=0.007, respectively), whereas those of TNFalpha (9.3+/-1.1 vs. 6.7+/-0.6 pg/ml) and sTNF-R2 (2464+/-145 vs. 1920+/-303 pg/ml) were not. Cholesterol (5.6+/-0.1 vs. 5.5+/-0.2 mmol/l) and LDL (3.5+/-0.1 vs. 3.6+/-0.2 mmol/l) were not different (both P>0.75). Patients had lower HDL (1.10+/-0.04 vs. 1.4+/-0.06 mmol/l, P=0.0004) and higher triglycerides (2.1+/-0.1 vs. 1.1+/-0.1 mmol/l, P=0.0006). Aetiology and the presence of cardiac cachexia did not influence the lipid profile. Correlations in patients: cholesterol vs. TNFalpha (r=-0.40, P=0.003), vs. sTNF-R1 (r=-0.24, P=0.08), vs. sTNF-R2 (r=-0.29, P<0.04); sCD14 vs. TNFalpha (r=0.44, P=0.005), vs. sTNF-R1: (r=0.65, P<0.0001), vs. sTNF-R2 (r=0.59, P<0. 0001). The sCD14/cholesterol ratio related powerfully to TNFalpha (r=0.60), sTNF-R1 (r=0.74), and sTNF-R2 (r=0.65, all P<0.0001). This sCD14/cholesterol ratio emerged as the strongest predictor of TNFalpha, sTNF-R1 and -R2 (all P<0.01), independently of renal and hepatic function, and conventional measures of disease severity. A cholesterol level <5.2 mmol/l (n=18) significantly predicted a poor clinical outcome (P<0.04, RR 3.5, 95% CI 1.1-11.0) independently of peak VO(2) (P=0.07), NYHA class (P=0.08), aetiology (P=0.14), and age, body wasting, sodium, LVEF, heart rate, and blood pressure (all P>0.20, follow-up 12 months, event rate 26%). CONCLUSION: Our data supports previous findings that lower, rather than higher cholesterol levels are associated with poor clinical outcome in patients with chronic heart failure. This relationship is unrelated to heart failure aetiology, and suggests that the classic risk profile is not longer relevant in established heart failure. The little-recognised ability of all lipoprotein fractions to bind endotoxin and to serve as natural buffer substances may explain this relationship between lower lipoprotein levels, higher cytokine concentrations and impaired prognosis.     

微生态制剂对重型肝炎患者血清细胞因子的影响

目的 研究微生态制剂对重型肝炎患者临床症状、血清生物化学指标和细胞因子的影响. 方法 112例重型肝炎患者,随机分为治疗组58例和对照组54例,治疗组在内科综合治疗的基础上加用双歧杆菌、嗜酸乳杆菌、肠球菌三联活菌胶囊和乳果糖口服4周,对照组单用内科综合治疗.观察两组患者治疗前后的临床症状、肝功能改善情况,采用酶联免疫吸附法检测治疗前后肿瘤坏死因子(TNF)α、白细胞介素(IL)-2、-6、-10的水平.结果 治疗组临床症状和肝功能改善均优于对照组,血清TNFα、IL-6水平治疗组分别为(109.4±14.7)pg/ml和(84.3±20.1)pg/ml,对照组分别为(128.7±18.8)pg/ml和(109.1±18.7)pg/ml,治疗组比对照组明显降低,t值分别为2.924、2.996,P值均＜0.01,差异有统计学意义.IL-2、-10治疗组分别为(59.8±12.2)pg/ml和(30.6±6.6)pg/ml,对照组分别为(47.1±6.7)pg/ml和(22.5±6.1)pg/ml,治疗组比对照组明显升高,t值分别为2.979、3.055,P值均＜0.01,差异有统计学意义.结论 微生态制剂能降低TNFα、IL-6含量,升高IL-10、-2水平,抑制炎性介质的产生和减轻免疫反应对肝细胞的损伤,从而改善临床症状和肝功能.     

人工肝支持系统对慢性乙型重型肝炎患者骨髓干细胞分化因子水平的影响

目的 探讨人工肝支持系统(ALSS)对慢性乙型重型肝炎患者血清骨髓干细胞(BMSC)分化因子水平的影响.方法 将50例慢性乙型重型肝炎患者分为ALSS组25例和对照组25例,对照组入院后予内科综合治疗,ALSS组在相同内科综合治疗的基础上于入院1周内开始接受ALSS治疗.采用ELISA法检测两组患者入院时和入院2周时的BMSC分化因子水平.统计学处理采用t检验.结果 ALSS组治疗前血清肝细胞生长因子(HGF)为(689.10±337.68)ng/L,成纤维细胞生长因子-4 (FGF-4)为(124.88±87.67) ng/L,表皮生长因子(EGF)为(323.85±44.40) ng/L,碱性成纤维细胞生长因子(bFGF)为(9.29±1.38)ng/L,治疗后血清HGF为(1081.50±356.66) ng/L,FGF-4为(110.76-79.71) ng/L,EGF为(347.80±71.73)ng/L,bFGF为(9.57±1.15) ng/L,其中HGF显著升高(t=10.042,P＜0.01),且升高幅度大于对照组(t=6.670,P＜0.01),FGF-4、EGF及bFGF改变差异无统计学意义.对照组HGF、FGF-4、EGF及bFGF在治疗前后均差异无统计学意义.结论 ALSS治疗可以提高慢性乙型重型肝炎患者血清HGF水平,同时不影响FGF-4、EGF和bFGF水平,可能有助于BMSC以转分化机制参与重型肝炎的肝细胞修复和再生.     

The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men

Testosterone has immune-modulating properties, and current in vitro evidence suggests that testosterone may suppress the expression of the proinflammatory cytokines TNFalpha, IL-1beta, and IL-6 and potentiate the expression of the antiinflammatory cytokine IL-10. We report a randomized, single-blind, placebo-controlled, crossover study of testosterone replacement (Sustanon 100) vs. placebo in 27 men (age, 62 +/- 9 yr) with symptomatic androgen deficiency (total testosterone, 4.4 +/- 1.2 nmol/liter; bioavailable testosterone, 2.4 +/- 1.1 nmol/liter). Compared with placebo, testosterone induced reductions in TNFalpha (-3.1 +/- 8.3 vs. 1.3 +/- 5.2 pg/ml; P = 0.01) and IL-1beta (-0.14 +/- 0.32 vs. 0.18 +/- 0.55 pg/ml; P = 0.08) and an increase in IL-10 (0.33 +/- 1.8 vs. -1.1 +/- 3.0 pg/ml; P = 0.01); the reductions of TNFalpha and IL-1beta were positively correlated (r(S) = 0.588; P = 0.003). In addition, a significant reduction in total cholesterol was recorded with testosterone therapy (-0.25 +/- 0.4 vs. -0.004 +/- 0.4 mmol/liter; P = 0.04). In conclusion, testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol. Twenty of these men had established coronary disease, and because total cholesterol is a cardiovascular risk factor, and proinflammatory cytokines mediate the development and complications associated with atheromatous plaque, these properties may have particular relevance in men with overt vascular disease.     

Gut-derived endotoxemia: one of the factors leading to production ofcytokines in liver diseases

AIM To understand the relationship between levels of endotoxin and cytokines in serum and to clarify thecause of cytokines change in liver diseases.METHODS Serum endotoxin level was determined by quantitative limulus amebocyte lysate chromogenicassay in 89 cases of acute and chronic liver diseases. Cytokines (TNF-a, IL-2, IL-6, IL-8, G-CSF) wereassayed by ELISA. Patients were divided into two groups based on oral administration of lactulose or not.Mean concentration of endotoxin and cytokines was compared before and 20 days after lactulose treatment.RESULTS The highest serum level of endotoxin was found in patients with cirrhosis (69.3±23.6pg/mL)and the lowest in patients with chronic hepatitis (28.4±7.9pg/mL), the moderate in patients with acutehepatitis (44.6±14.3pg/mL) (P<0.01). Serum levels of TNF-a, IL-2, IL-6, IL-8, G-CSF were higher inpatients with acute hepatitis than those with chronic hepatitis (P<0.05). No difference was noted betweenchronic hepatitis and cirrhosis (P >0.05). In all cases, serum levels of endotoxin were positively correlatedwith the concentration of TNF-a (r=0.555, P<0.05), IL-6 (r=0.531, P<0.01), IL-8 (r=0.440,P<0.05) and G-CSF (r =0.440, P<0.05), but not with IL-2 (r =0.10l, P<0.05). The decrease of serumlevels of endotoxin was greater in patients taking lactulose than controls (25.6±14.4pg/mL, n = 49 cases vs.10.9±9.Spg/mL, n = 40 cases, P < 0.01), the recovery from endotoxemia was higher in group withlactulose treatment than in controls (94.7%, n = 19 vs 36.4%, n = 22, P < 0.01 ). The decrease ofendotoxin resulted in decreases of TNF-a, IL-6, IL-8, G-CSF, ALT, AST and TB.CONCLUSION Endotoxemia is common in liver diseases, which could induce production and release ofcytokine from monocytes and macrophages and has harmful effects on hepatocytes. Treatment with lactulosecould decrease serum levels of endotoxin and cytokines, suggesting that lactulose could protect liver cells frominjury by reducing the absorption of endotoxin in intestine.