血清精氨酸代琥珀酸裂解酶的测定在肝病诊断中的意义

目的探讨血清精氨酸代琥珀酸裂解酶（ASL）对肝病的诊断效能。方法测定291例肝病患者、247例非肝病患者和32名健康对照血清ASL和ALT、AST、GGT、LDH、ALP活性及TBil浓度；其中31例肝病患者进行了病理组织学检查。结果ROC曲线显示ASL对判断肝病的敏感度为100．0％，特异性为91．1％（分界值=8．0U／L）；ALT和AST的敏感度为97．60%和83．8％，特异性仅分别为24．7％和28．3％（分界值=40．0U／L）。ASL在不同肝病的变化情况是肝癌〉急性肝炎〉肝硬化〉慢性肝炎；ASL浓度[（86．9±26．5）u／L]与肝病理组织学炎症活动度计分（9．83±3．36）呈正相关（r=0．417，P=0．019）。结论ASL诊断肝病的敏感度、特异性优于AST和ALT，是肝病诊断的有用指标。     

γ-干扰素、腺苷脱氨酶对结核和非结核性胸腔积液的诊断价值

目的联合检测胸腔积液和血清 γ-干扰素浓度及腺苷脱氨酶水平,探讨其对结核和非结核性胸腔积液的鉴别诊断价值。方法应用酶联免疫吸附法和速率法,检测46例结核性胸液、42例非结核性胸液及其相应血清中IFN-γ浓度和ADA水平,并与30例对照组比较。结果结核性胸膜炎患者胸液IFN-γ浓度为（497．13±200．79）ng／L,明显高于癌性胸液组（72．16±78．58）ng／L和漏出性胸液组（13．61±5．92）ng／L（P〈0．001）。结核性胸膜炎患者胸液ADA水平（54．45±15．33U／L）明显高于癌性胸液组（18．67±16．54）U／L和漏出液组（8．97±1．96）U／L,P〈0．001。结论联合检测胸液INF-γ浓度和ADA活性对结核性胸腔积液的鉴别诊断有较高的临床应用价值。     

静脉应用胺碘酮致急性肝损害六例临床分析

目的分析静脉应用胺碘酮致急性肝损害的临床特点及转归。方法对我院2001年1月至2005年1月静脉应用胺碘酮后致急性肝损害6例患者应用的适应证、剂量、肝损害出现的时间及转归进行分析。结果6例患者出现急性肝损害前静脉应用胺碘酮剂量为290—3000（1322．5±973．8）mg。6例患者用药后（40±29）h肝酶开始升高，天门冬氨酸氨基转移酶（AST）峰值为199—9885（2992±3453）U／L，丙氨酸氨基转移酶（ALT）峰值为247—6750（2583±2402）U／L。停药护肝降酶治疗后（28±17）d肝酶降至正常。结论静脉应用胺碘酮可以导致急性肝损害，应及时监测肝脏功能。     

血浆置换对重型肝炎患者血清生长激素-胰岛素样生长因子轴的影响

目的了解重型肝炎患者血清生长激素-胰岛素样生长因子轴（GH—IGF）在血浆置换（PE）前后的变化和意义。方法治疗组46例重型肝炎患者均给予内科综合治疗及PE治疗，PE治疗前后分别测定血清GH、IGF-2及肝生化指标。正常对照组同时检测GH、IGF-2。结果重型肝炎组与正常组比较，血清GH水平明显升高[（3．99±2．87）ug／L对（1．53±0．89）ug／L，P〈0．01]，IGF-2水平明显降低[（0．32±0．13）ug／L对（0．44±0．14）ug／L，P〈0．01]。重型肝炎存活组与死亡组比较，GH升高差异无统计学意义，而IGF-2明显高于死亡组。PE治疗有效率为82．6％，肝功能及PTA好转（P〈0．05或P〈0．01），GH变化差异无统计学意义[（3．99±2．87）ug／L对（3．53±2．32）ug／L，P〉0．053，IGF-2明显升高[（0．32±0．13）ug／L对（0．41±0．14）ug／L，P〈0．01]，GH与IGF-2呈负相关（r=-0．35，P〈0．01）。结论重型肝炎患者GH—IGF轴发生显著改变，PE是治疗重型肝炎的方法之一，对GH—IGF轴具有调节作用。     

重型肝炎患者内毒素血症与并发高乳酸血症和低血糖的关系

目的：探讨重型肝炎患者内毒素血症与并发高乳酸血症和低血糖的关系及机制。方法：48例慢性重型肝炎患者作为实验组，20例体检健康者为对照组，分别检测其血清内毒素、乳酸、血糖、总胆红素及乳酸脱氢酶的活力。结果：48例慢性重型肝炎患者低血糖发生率为52．2％，发生低血糖的患者内毒素水平为（1.87±0．91）EU／ml，正常血糖患者内毒素水平为（1．01±0．21）EU／ml，两者比较差异有显著性意义（P〈0．05）；高乳酸血症发生率为93．5％，发生高乳酸血症的患者内毒素水平为（1．85±0．92）EU／ml，正常乳酸水平的患者内毒素水平为（1．03±0．04）EU／ml，两者比较差异有显著性意义（P〈0．05）；48例患者中乳酸脱氢酶升高者有30例，占62．5％，其血清乳酸水平为（10．92±3．27）mmol／L，乳酸脱氢酶正常的患者乳酸水平为（6．51±0．47）mmol／L，两者比较差异有显著性意义（P〈0．05）；乳酸脱氢酶升高者血糖为（1.61±1．47）mmol／L，乳酸脱氢酶正常的患者血糖为（3．91±0．58）mmol／L，两者比较，差异有显著性意义（P〈0．05）。20例正常人的血糖、乳酸、总胆红素值均在正常值参考范围内，与实验组比较，差异有显著性意义（P〈0．05）。结论：重型肝炎患者出现严重的内毒素血症时可通过影响乳酸脱氢酶的活性而增强机体糖酵解功能，导致高乳酸血症和低血糖的发生。     

肾综合征出血热患者血清可溶性细胞因子、粘附分子及肝肾功能的变化

目的探讨血清可溶性TNF-α、IL-1β、转化生长因子-β1（TGF-1β）、E-选择素（E-sel）和L-选择素（L-sel）在肾综合征出血热（HFRS）发病机制中的作用。方法41例HFRS患者（轻症组22例，重症组19例）纳入研究，按病期采血，分别采用放射免疫法检测TNF-α、IL-1β，ELISA法检测TGF-β1、E-sel和L-sel，自动生化仪检测肝、肾功能和PLT计数。结果从发热期至多尿期，血清IL-1β、TNF-α、E-sel和L-sel水平均升高，其峰值与对照组比较，分别为（0．56±0．10）μg／LH5（0．19±）．06）μg／L、（2．41±1．61）μg／L比（0．824-0．16）μg／L、（198．4±29．2）μg／L比（56．4±25．8）μg／L、（1372．5±137．3）μg／L比（1089．9±137．9）μg／L，差异有统计学意义（P值均〈0．01）。动态观察，上述细胞因子和粘附分子的变化曲线与ALT、BUN的变化趋势一致。血清TGF-1β、TGF-β1／IL-1β和TGF-β1／TNF-α比值在病程前三期均显著降低，与PLT的变化趋势相似。结论HFRS急性期血清IL-1β、E-sel、L-sel升高和TGF-β1水平下降是造成失控性全身炎性反应和肝、肾功能损害的重要因素，在HFRS发病机制中起重要作用；合理的对症治疗和适量使用免疫调节剂可改善预后。     

肝苏颗粒对实验性黄疸大鼠肝功能的保护及其机制

目的 观察肝苏颗粒对实验性黄疸大鼠的保护作用及其机制的初步探讨。方法 采用α-萘异硫氰酸酯（ANIT）灌胃制备大鼠黄疸模型，共60只大鼠，设正常组、模型组、熊去氧胆酸（UDCA）组、肝苏颗粒小剂量组和肝苏颗粒大剂量组，检测不同组血清ALT、TBil和一氧化氮（NO）、IL-6的变化，流式细胞仪检测肝细胞凋亡，免疫组化检测肝细胞Bcl-2、Bax蛋白的表达。结果 肝苏颗粒大、小剂量治疗组和UDCA组与模型组比较，ALT及TBil降低明显，ALT分别为（547．20±79．41）U／L、（573．34±68．79）U／L、（535．60±69．39）U／L、（642．30±92．70）U／L，TBil分别为（47．10 ± 11．54）μmol／L,（50．87±13．46）μmol／L、（45．22±14．46）μmol／L.（66．19±10．67）μmol／L，差异有统计学意义（P〈0．05或P〈0．01）。肝苏颗粒治疗组和UDCA组NO、IL-6水平与模型组比较下降显著，差异有统计学意义（P〈0．01或P〈0．05）。肝苏颗粒治疗组、UDCA组与模型组比较，肝细胞凋亡率下降，差异有统计学意义（P〈0．01或P〈0．05）；肝苏颗粒大剂量治疗组、uDCA组Bcl～2和Bax阳性表达及Bax／Bcl-2相对比率明显低于模型组，差异有统计学意义（P〈0．01或P〈0．05）。结论 肝苏颗粒对实验性黄疽大鼠的肝功能具保护作用，影响血清NO、IL-6及抑制肝细胞凋亡可能是其退黄、恢复肝脏功能的作用机制之一。     

非小细胞肺癌患者术后血清VEGF动态变化与血小板的相关性研究

背景与目的已有研究表明：非小细胞肺癌（non-small cell lung cancer, NSCLC）患者手术切除原发肿瘤后其血清中血管内皮生长因子（vascular endothelial growth factor, VEGF）浓度显著升高,血小板可能是血清中VEGF的主要来源。本研究的目的是探讨NSCLC患者术后血清VEGF浓度的动态变化及其与血小板之间的关系。方法应用酶联免疫吸附试验（enzyme linked immunosorbent assay, ELISA）检测法,监测76例非小细胞肺癌患者术前、术后1天及7天血清VEGF的浓度,同期检测血小板的浓度。结果①NSCLC患者术前、术后1天及7天血清VEGF分别为（842．06±52724）pg／mL、（1119．28±609．62）pg／mL、（1574．09±873．38）pg／mL,组间比较差异具有统计学意义（P=0．000）;②NSCLC患者术前、术后1天及7天血小板计数分别为（230．42±82．56）×10^0/L、（196．47±8148）×10^9/L、（237．90~86．94）×10^9/L,术后1天最低（P=0．000）,③术后7天在血小板高于均数组血清VEGF浓度为（1842．86±1006．63）pg／mL,低于均数组为（1398．81±734．00）pg／mL,两组有统计学差异（P=0．043）。结论NSCLC患者术后血清VEGF浓度显著升高,血小板计数高的患者中,其血清VEGF浓度升高更为明显。     

慢性乙型肝炎病毒携带者的病理与临床及预后分析

目的了解慢性HBV携带者的肝脏组织病理与临床的关系,探讨其临床转归和影响预后的因素。方法对90例行肝穿刺活组织检查的慢性HBV携带者的临床和病理资料进行分析并持续随访观察。结果（1）90例患者平均随访时间118（29～260）周。（2）15例（16．7％）患者肝穿刺检查示无肝脏组织学病变,75例患者有炎症病变,其中G1期54例（60．0％）,G2期21例（23．3％）；肝纤维化分期S1期42例（46．7％）,S2期21例（23．3％）。（3）肝纤维化分期S2期的患者平均年龄为（45．9±16．4）岁,与S0期和S1期患者平均年龄[分别是（38．9±13．6）岁和（42．7±14．8）岁]相比较,差异有统计学意义（P＜0．05）。（4）炎症分级为G0期患者的血清ALT水平[（13．4±3．6）U/L]与G1和G2期患者的血清ALT水平[分别为（27．3±4．3）U/L和（31．8±7．2）U/L]相比较,差异有统计学意义（P＜0．05）。（5）肝组织炎症分级与HBeAg阳性与否及血清HBV DNA定量水平无关（P＞0．05）,肝组织纤维化分期与血清HBV DNA定量水平无关（P＞0．05）。纤维化程度高者以HBeAg阴性者为多,差异有统计学意义（P＜0．05）。（6）超声定量检查脾脏长度和厚度在肝纤维化分期S2期与S0、S1期患者比较,差异有统计学意义（P＜0．05）。（7）随访中60例血清ALT持续正常（A组）,22例血清ALT短暂升高（B组）,8例血清ALT持续升高（C组）。肝穿刺活组织检查时肝纤维化分期S2期患者所占百分比在A组和B组低于C组患者,但S0期患者所占百分比高于C组患者,差异有统计学意义（P＜0．05）。（8）年龄、肝纤维化分期是进展为肝硬化的独立预测因素。结论多数慢性HBV携带者肝脏组织学有轻度炎症,不伴有或伴有轻度肝纤维化,且肝纤维化随病程发展有不同程度进展。随访研究表明这些携带者中部分在近期内需要抗病毒治疗。     

肝硬化患者腹水中细菌DNA的检测及临床意义

目的 利用PCR测序方法检测肝硬化患者腹水中的细菌DNA，探讨肝硬化患者发生细菌移位的高危因素及其后果。方法 在细菌16SrRNA基因保守区设计一对通用引物，对37份肝硬化患者腹水标本进行扩增，腹水中细菌DNA阳性者纯化后经核苷酸测序鉴别细菌种类；同时对患者的临床症状及实验室检查结果进行统计分析。结果 37份腹水标本中有9份获得530bp细菌DNA片段，占24．3％。测序共检测出4种细菌，其中大肠埃希菌6例，表皮葡萄球菌、溶血性链球菌、阴沟肠杆菌各1例；统计分析表明，腹水中细菌DNA阳性和阴性两组肝硬化患者在Child-Pugh积分（12．3±0．8，10．9±1．2）、上消化道出血的发生率（3例，1例）、血清TBil水平[（395．5±216．6）μmol／L，（192．7±206．3）μmol／L]、凝血酶原活动度[（31．3±9．7）％，（50．4±15．1）％]、腹水总蛋白浓度[（4．1±2．8）g／L，（7．9±5．2）g／L]、外周血WBC总数[（12．3±7．5）×10^9／L，（5．3±4．1）×10^9／L]等方面比较，差异有统计学意义（P〈0．05）。结论 PCR测序方法可应用于肝硬化患者腹水中细菌DNA的检测及细菌移位的研究；肝功能损害、腹水调理活性低下和上消化道出血是肝硬化患者发生细菌移位的高危因素和后果。     

肺血栓栓塞症患者凝血纤溶系统及肺血管内皮功能的变化

目的探讨肺血栓栓塞症(PTE)患者体内凝血纤溶系统及肺血管内皮功能的变化及其临床意义。方法采用酶联免疫吸附测定(ELISA)检测80例PTE患者(急性大面积PTE组20例、非大面积PTE组60例)、40名正常人(对照组)的血D-二聚体(D-D)、组织型纤溶酶原激活剂(t-PA)、纤溶酶原激活剂抑制物1(PAI-1)、血浆蛋白S(Ps)、血浆蛋白C(Pc)、凝血酶调节蛋白(TM)、抗心磷脂抗体(ACA)、同型半胱氨酸(Hcy)含量;采用发色底物法检测抗凝血酶Ⅲ活性(AT-Ⅲ)。结果急性大面积PTE组患者血D-D、t-PA、PAI-1、Ps、TM、含量分别为(1.46±0.62)mg/L、(11.4±6.9)μg/L、(88.2±27.5)μg/L、(22.40±9.40)mg/L、(6.8±1.1)μg/L,非大面积PTE组分别是(0.92±0.27)mg/L、(6.6±1.5)μg/L、(60.1±26.1)μg/L、(23.90±10.70)mg/L、(6.3±1.5)μg/L,均显著高于正常对照组的(0.38±0.10)mg/L、(4.7±1.4)μg/L、(35.7±9.2)μg/L、(16.10±6.20)mg/L、(3.0±0.5)μg/L(分别P<0.01、<0.05)。急性大面积PTE组患者血AT-Ⅲ含量为(86.0±11.8)%,非大面积PTE组为(90.1±9.0)%,显著低于正常对照组的(102.6±9.20)%(P分别<0.01、0.05)。两PET组患者ACA-IgG、IgM、IgA显著高于正常对照组,差异有统计学意义(P<0.05)。结论PTE患者存在凝血纤溶系统功能失衡和肺血管内皮损伤。     

Effects of tirofiban plus heparin versus heparin alone on troponin I levels in patients with acute coronary syndromes

Elevated serum troponins following an acute coronary syndrome (ACS) predict a poor clinical outcome. Glycoprotein (GP) IIb/IIIa inhibitors reduce adverse clinical outcomes in patients with ACS, although their effect on serum troponin I (TnI) in this setting has not been described. We therefore studied the effects of the GP IIb/IIIa inhibitor tirofiban on serum TnI levels in a group of patients in the Platelet Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial. Serial blood samples were obtained in 53 patients receiving the combination therapy of tirofiban/heparin and in 52 receiving heparin alone, and were analyzed for baseline, peak, and mean concentrations of TnI. Baseline TnI levels were not different between the combination therapy and heparin-only groups (1.6 +/- 3.0 vs 3.1 +/- 6.7 ng/ml, p = 0.15). The peak TnI level was significantly lower in the combination therapy group than in the heparin group (5.2 +/- 8.3 vs 15.5 +/- 29.1 ng/ml, p = 0.017), and mean levels over the initial 24-hour period were also significantly lower in the combination therapy group (3.2 +/- 5.0 vs 8.5 +/- 14.8 ng/ml, p = 0.016). In univariate analysis, combination therapy was associated with lower TnI levels, whereas in a multivariate model, the lower peak and mean TnI levels as a consequence of tirofiban/heparin compared with heparin monotherapy remained significant (peak, p = 0.029; mean, p = 0.035). Among patients with negative TnI at baseline, treatment with the combination of tirofiban/heparin compared with heparin monotherapy still resulted in significantly lower peak (2.5 +/- 5.4 vs 14.6 +/- 32.8 ng/ml, p = 0.024) and mean (1.2 +/- 2.6 vs 6.9 +/- 15.8 ng/ml, p = 0.029) TnI levels. In patients with ACS, therapy with the combination of tirofiban and heparin (compared with heparin treatment alone) resulted in lower serum TnI levels, suggesting reduced myocardial injury.     

急性肺血栓栓塞症患者溶栓抗凝治疗后深静脉血栓的变化

目的 观察急性肺血栓栓塞症(PTE)患者溶栓抗凝治疗后深静脉血栓(DVT)的变化.方法 从急性PTE溶栓与抗凝治疗多中心研究中选取确诊的于溶栓抗凝治疗前后行下肢静脉超声检查的PTE患者362例,观察治疗前后深静脉血栓的变化.结果溶栓抗凝治疗后14 d与治疗前相比,DVT明显减少(x2=22.667,P<0.001),但有11.6%的患者出现新发或再发DVT.溶栓治疗者血流改善率为56.5%,抗凝治疗者为47.8%,二者间差异无统计学意义(x2=1.435,P=0.231).3个月随访,有30.4%的患者DVT仍未恢复正常,另有10.4%的患者经超声检查发现DVT.结论 溶栓抗凝治疗后14 d,DVT的治愈率较低,新发或再发率较高,溶栓治疗的血流改善与抗凝治疗相仿.短期治疗尚不能显著改善DVT的预后.     

Hyper-CK-emia in pediatric celiac disease: prevalence and clinical importance

Hyper-transaminasemia (HT) is a well-known laboratory sign of celiac disease (CD); however, hyper-creatine phosphokinase (CK)-emia (HCK) is not so familiar. As there are reported cases of myopathy associated CD in the literature, we aimed to investigate serum CK levels of children with CD. Newly diagnosed 126 children were included. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and CK levels were determined. Mean age was 8.7+/-4.4 years (11 mo to 18 y). Of patients, 77 (61.1%) had classic form, 49 (38.9%) had atypical form. Elevated levels of AST, ALT, and CK, respectively, were found in 65 (51.6%), 45 (35.7%), and 50 (39.7%) patients. Isolated HCK was detected in 9 (7.1%) patients. AST, ALT, and CK were all elevated in 29 (23.0%) children. Mean serum AST, ALT, and CK levels were found as 56.1+/-53.7 U/L (11 to 403), 44.7+/-44.0 U/L (7 to 290), and 258.0+/-686.5 U/L (36 to 5956), respectively. In 95 (75.4%) children, AST/ALT value was greater than 1, and in 19 (15.1%) it was greater than 2. We found positive correlations with the level of CK and AST, and ALT (P=0.01). CK level was inversely correlated with hemoglobin and cholesterol levels (P=0.013 and 0.007). In conclusion, this is the first study, which determined elevated serum levels of CK in CD and demonstrated that HCK is as common as HT in children with CD. We emphasize that HT seen in CD is not necessarily a sign of liver injury, but may also be due to myopathy.     

Normal serum alanine aminotransferase activity in uncomplicated obesity

AIM: To evaluate serum alanine aminotransferase (ALT) activity in a well-characterized group of uncomplicated obese subjects and its correlation with insulin resistance, plasma adiponectin, and leptin concentrations. METHODS: One hundred and five uncomplicated obese subjects (87 women, 18 men, age 34.3±9.6 years, BMI 39.9±8.3 kg/m2)were studied. Serum ALT activity was evaluated. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp (M index) and fasting insulin. Plasma leptin and adiponectin levels were also measured. RESULTS: Serum ALT concentration in the whole group of uncomplicated obese subjects was 17.73±6.33 U/L with none of the subjects presenting ALT levels greater than 43 U/L and only 9 (11%) women and 3 (19%) men showed ALT levels >19 and >30 U/L for women and men, respectively. No significant difference was detected in serum ALT levels between severe obese subjects (BMI >40 kg/m2) and those with BMI <40 kg/m2 (18.63±6.25 vs 17.26±6.02 U/L). ALT was significantly correlated with fasting insulin (r=0.485, P= 0.02) and triglycerides (r= 0.358, P=0.03). CONCLUSION: Serum ALT activity is practically normal in uncomplicated obese subjects, independently of their obesity degree. These findings suggest the role of obesityrelated comorbidities and not of BMI as main risk factors for elevated ALT levels in obese subjects.     

腺苷脱氨酶诊断结核性胸膜炎价值的再评价

目的 探讨胸腔积液和血清中腺苷脱氨酶(ADA)对鉴别结核性胸膜炎及恶性胸腔积液的临床价值.方法 回顾性分析91例经内科胸腔镜胸膜活检病理确诊为结核性胸腔积液(结核组49例)和恶性胸腔积液(恶性组42例)患者的胸腔积液及血清中ADA活性,应用受试者工作曲线(ROC曲线)确定结核性胸膜炎患者胸腔积液ADA的最佳临界值.结果 结核组胸腔积液ADA活性和胸腔积液ADA与血清ADA比值分别为(46±26)U/L和4.1±4.0,明显高于恶性组的(16±8)U/L和1.7±1.2,差异均有统计学意义(t值分别为7.383和3.852,均P＜0.01),结核组和恶性组的血清ADA活性分别为(13±5)U/L和(12±6)U/L,差异无统计学意义(t=1.582,P＞0.05).应用ROC曲线确定胸腔积液ADA诊断结核性胸膜炎的最佳临界值为28.7 U/L,灵敏度为75.5%,特异度为95.2%.结论 胸腔积液ADA活性可以作为鉴别结核性和恶性胸腔积液的重要指标,对结核性胸膜炎有较高的临床诊断价值,而血清ADA活性对鉴别两者无临床意义.     

丝裂原激活蛋白激酶信号通路在肝脏缺血预处理细胞保护效应中的作用

目的 研究p44/42丝裂原激活蛋白激酶(MAPK)信号通路在肝脏缺血预处理细胞保护效应中的作用。方法 建立体内和体外肝脏缺血预处理模型,应用蛋白激酶C(PKC)抑制剂和MAPK抑制剂,通过检测p44/42MAPK磷酸化水平,细胞活力,血清天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)的活性变化,同时观察光镜细胞形态学损害,对相关数据进行统计学处理。 结果 体内和体外的缺血预处理两部分实验都观察到相似的结果。和缺血再灌注组比较,预处理组的p44/42 MAPK磷酸化水平显著增高,肝细胞结构损伤改变较小,血清ALT、AST水平显著降低,缺血再灌注组的ALT、AST水平分别为(762.8±130.5)U/L和(820.9±111.3)U/L,预处理组的ALT、AST水平分别为(281.0±35.6)U/L和(407.7±73.7)U/L;和缺血预处理组相比,PKC抑制剂组和丝裂原蛋白激酶(MEK)抑制剂组相应的观察指标呈相反的变化,p44/42 MAPK磷酸化激活显著减少,肝组织细胞结构出现较明显的损伤改变,血清ALT、AST水平显著升高,PKC抑制剂组和MEK抑制剂组的ALT、AST水平分别为(645.61±90.4)U/L、(678.6±136.5)U/L和(466.2±82.8)U/L、(732.9±91.1)U/L。 结论 肝脏缺血预处理细胞保护作用中,p44/42 MAPK通路起到至关重要的作用。     

Pathophysiology of impaired right and left ventricular function in chronic embolic pulmonary hypertension: changes after pulmonary thromboendarterectomy

STUDY OBJECTIVES: This study sought to evaluate the pathophysiology of left and right heart failure in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who were hospitalized to undergo pulmonary thromboendarterectomy (PTE). DESIGN: Thirty-nine patients (16 women and 23 men; mean +/- SD age, 55+/-12 years) with severe CTEPH were examined before and 13+/-8 days after PTE by way of transthoracic echocardiography and right heart catheterization. MEASUREMENTS AND RESULTS: Examination results confirmed in all cases that before surgery the right ventricles were enlarged and systolic function was impaired. Moderate to severe tricuspid valve regurgitation was observed. Left ventricular eccentricity indexes reflected a leftward displacement of the interventricular septum. End-diastolic left ventricular size and systolic function had decreased, and the left ventricular filling pattern showed impaired diastolic function. After surgery, mean pulmonary artery pressure was significantly lower (48+/- 10 mm Hg vs. 25+/-7 mm Hg; p<0.05). The calculated end-diastolic and end-systolic right ventricular areas had decreased: 30+/-7 cm(2) vs 21 +/-5 cm(2) (p<0.05) and 24+/-6 cm(2) vs. 14+/-4 cm(2) (p<0.05), respectively. Right ventricular fractional area change had increased (20+/-7% vs. 33+/-8%; p<0.05). Most of the patients exhibited a marked decrease in the severity of tricuspid regurgitation. Septal motion, left ventricular systolic function, and diastolic filling pattern returned to normal values (early to late diastolic left ventricular inflow ratio, 0.70+/-0.33 vs. 1.35+/-0.51; p<0.05). The mean cardiac index also improved (2.7+/-0.6 L/min/m(2) vs. 3.7+/-0.8 L/min/m(2)). CONCLUSIONS: In CTEPH, functions are impaired in the right as well as the left ventricles of the heart. Improved lung perfusion and the reduction of right ventricular pressure overload are direct results of PTE, which in turn bring a profound reduction of right ventricular size and a recovery of systolic function. Normalization of interventricular septal motion as well as improved venous return to the left atrium lead to a normalization of left ventricular diastolic and systolic function, and the cardiac index improves.     

复方861治疗慢性乙型肝炎肝纤维化与早期肝硬化的临床研究

目的观察复方861对慢性乙型肝炎肝纤维化、早期肝硬化患者的抗肝纤维化效果.方法采用随机、双盲、安慰剂对照的方法,以治疗前后肝穿病理组织学为评价指标,对6家医院的慢性乙型肝炎肝纤维化患者136例,按照随机编码分别服用复方861胶囊或安慰剂胶囊共24周,观察治疗前后患者症状、体征、肝功能、肝纤维化指标[IV胶原(C Ⅳ)、层黏连蛋白(L N)、Ⅲ型前胶原N端肽(P ⅢP)、透明质酸(HA)]、基质金属蛋白酶1、2、9(MMP1、2、9)及金属蛋白酶组织抑制因子(TIMP1、2)水平以及肝病理组织学的变化.结果 5 2例治疗组、5 0例安慰剂组的患者完成治疗前后肝穿刺.治疗组患者治疗前、后血清丙氨酸氨基转移酶(ALT)分别为(68.2±68.6)U/L和(45.9±26.1)U/L、天冬氨酸氨基转移酶(AST)分别为(60.4 ± 62.6)U/L和(46.7 ± 39.0)U/L,安慰剂组患者治疗前、后血清ALT分别为(65.3±48.3)U/L和(85.4±115.5)U/L,AST分别为(60.4±44.6)U/L和(77.6±89.6)U/L,两组比较差异均有显著性,t=2.315和t=2.168,P＜0.05.治疗组血清HA、PⅢP、CⅣ、LN水平均较治疗前有所下降,但与安慰剂组相比,差异无显著性.治疗组治疗前、后血清TIMP1分别为(172.0±79.6)ng/m1和(133.5 ± 66.8)ng/ml,MMP9分别为(116.1±88.2)ng/ml和(80.4±79.0)ng/ml,较治疗前均明显下降,f=2.723和t=2.433,P＜0.05.复方861治疗前、后血清TIMP1/MMP1比值分别为4 8.3±96.3和19.9 ± 28.0,较治疗前下降,而对照组则较治疗前升高,治疗前后差值相比,两组差异有显著性,t=2.248,P＜0.05.治疗组治疗前、后肝组织炎症计分分别为14.0±6.0和10.2±6.1、纤维化计分分别为11.9±6.5和8.2=4.5,病理图像分析胶原相对含量分别为18.9%±9.5%和14.9%± 8.4%,t值为3.354～2.202,P值均＜0.05;S2期逆转率为38.9%,S 3期为53.3%,S4期为78.6%,总逆转率52.0%;安慰剂组分别为14.3%、25.0%、41.7%、20.0%,两组差异有显著性,x2值为9.766～4.478,P值均＜0.05.复方861治疗组未见明显不良反应.结论复方861治疗慢性乙型肝炎肝纤维化、早期肝硬化是可以逆转的.