Protective effects of pLNCX-SOD gene transfection on hepatocyte injury induced by obstructive jaundice in rats

BACKGROUND: H ydrophobic bile acids lead to the generation of oxygen free radicals in mitochondria. Accordingly, this study is to investigate if gene delivery of superoxide dismutase (SOD) will reduce hepatocyte injury caused by experimental cholestasis. METHODS: The recombinant of pLNCX-SOD gene packaged with lipofection of AMINE was transfected into hepatocytes in vitro, which stably expressed the SOD gene. RESULTS: After transfection, hepatocytes enhanced the protective effect against injury to bile and the toxicity of serum in obstructive jaundice. The inhibition of bile at the concentration of 2% (v∶v, bile: DMEM 1∶50) decreased obviously from (78.80±12.35)% to (43.35±9.69)% in 12 hours, from (82.55±11.27)% to (-26.64±7.66)% in 24 hours, and from (83.83±18.69)% to (-19.27±14.38)% in 48 hours, compared with that of the untransfected cells (P<0.01). The inhibition of serum at the obstructive jaudice concentration of 2.5% was obviously decreased from (89.72± 1.52)% to (14.68±14.33)% in 12 hours, from (92.2±11.27)% to (41.39±7.66)% in 24 hours, and from (94.25±8.96)% to (22.71±4.38)% in 48 hours (P<0.01). CONCLUSION: Hepatocytes transfected with the pLNCX-SOD gene could obviously be resistant to the toxicity of bile and serum from rat with obstructive jaundice.     

Protective effects of glutamine preconditioning on ischemia-reperfusion injury in rats

BACKGROUND:Hepatic ischemia-reperfusion injury is a common phenomenon in hepatic surgical procedures and can result in further severe damage.This study aimed to investigate the protective effects of glutamine preconditioning on hepatic ischemia-reperfusion injury in rats and its dose-dependency. METHODS:Thirty-two healthy male Wistar rats were randomly divided into four groups(n=8 per group).One group received 0.9%NaCl(control)and the other three received glutamine(Gln groups)4 hours before ischemia.The Gln...     

Reduction of urinary albumin excretion by thromboxane synthetase inhibitor, OKY-046, through modulating renal prostaglandins in patients with diabetic nephropathy

We evaluated the effects of thromboxane synthetase inhibitor, OKY-046, on urinary albumin and prostaglandin (PG) excretion in 14 patients with non-insulin-dependent diabetes mellitus (NIDDM).

Urinary excretion of 6-keto-PGF₁ (a stable metabolite of PGI₂), TXB₂ (a stable metabolite of TXA₂) and PGE₂ in NIDDM patients was comparable with that in control subjects. However, the urinary 6-keto-PGF₁/TXB₂ ratio in NIDDM patients with both micro- and macroalbuminuria was significantly (P < 0.001) lower than that in the controls.

By a single administration of OKY-046 (40 mg, i.v.) to the diabetic patients, urinary TXB₂ excretion significantly (P < 0.05) decreased from 169.7 ± 23.9 to 140.2 ± 17.9 ng/gCr, but urinary 6-keto-PGF₁ and PGE₂ excretion did not change significantly. The urinary 6-keto-PGF₁/TXB₂ ratio thus significantly (P < 0.01) increased from 1.02 ± 0.13 to 1.73 ± 0.41 as associated with significant increments in urine volume (P < 0.05), urinary sodium excretion (P < 0.01) and creatinine clearance (P < 0.05).

Of 14 diabetic patients, 7 with macroalbuminuria (albumin index exceeding 100 mg/gCr) were orally given OKY-046 (600 mg/day) for 8 weeks. After this period, the urinary albumin index significantly (P < 0.05) decreased from 524.9 ± 149.6 to 317.6 ± 90.6 mg/gCr. Urinary PG excretion did not change significantly, although the urinary 6-keto-PGF₁/TXB₂ ratio significantly (P < 0.01) increased from 1.33 ± 0.16 to 2.42 ± 0.65 and decreased to 1.09 ± 0.15 (P < 0.01) following termination of this drug. Similarly, creatinine clearance significantly (P < 0.01) increased, from 56.3 ± 14.1 to 69.4 ± 15.1 ml/min. During the period of 8 weeks, no significant alteration occurred in systemic blood pressure or glycemic control.

In conclusion, OKY-046 has a beneficial effect on albuminuria in diabetic nephropathy by modulating altered renal PGs synthesis, which leads to a change in renal hemodynamics.     

Protective effects of HGF-MSP chimer (metron factor-1) on liver ischemia-reperfusion injury in rat model

OBJECTIVE: It has been reported that metron factor-1 (MF-1), an engineered chimerical factor containing selected functional domains of hepatocyte growth factor and macrophage-stimulating protein (HGF–MSP), could prevent apoptosis and have an anti-inflammatory effect. In this study, we investigate the protective effect of MF-1 on liver ischemia-reperfusion (I/R) injury. METHODS: Overall 30 Sprague Dawley rats were randomly divided into three groups: the I/R model group (n = 12), the MF-1 treatment group (n = 12), and the sham-operated group (n = 6). Liver I/R injury was induced by clamping the blood supply to the left and median lobes of liver by an atraumatic clamp for 90 min, then removing the clamp and allowing reperfusion. Blood samples were obtained on days 1, 2, 3 and 7 to assess liver biochemistry and the histology of liver tissue. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), endothelial nitric oxide synthase and inducible nitric oxide synthase were measured. In addition, the anti-oxidative effect of MF-1 on hepatocytes was assessed in vitro. RESULTS: MF-1 treatment improved the rat survival rate significantly (P < 0.05). Liver biochemistry and histological changes were significantly ameliorated. MDA increased and SOD and NO decreased in the liver tissue. In vitro, MF-1 protected the human hepatic cell line HL-7702 from damage of oxidative stress. CONCLUSION: MF-1 could protect the liver from I/R injury, which might involve the reduction of oxygen free radicals and the increase of NO synthesis in an injured liver.     

促血小板生成素对大鼠脑缺血再灌注脑组织的保护作用

目的探讨促血小板生成素对大鼠局灶性脑缺血再灌注损伤后的保护作用及机制。方法采用线栓法阻断大鼠大脑中动脉血流制成局灶性脑缺血再灌注损伤模型。将60只雄性SD大鼠随机分成促血小板生成素(TPO)组、缺血再灌注组、假手术组和正常组。于缺血开始时TPO组给予TPO 5μg/kg腹腔注射;缺血再灌注组给予等剂量生理盐水。分别于再灌注6、12、24、48 h后断头取脑、切片,进行HE染色、Bcl-2免疫组化染色和细胞凋亡检测。结果缺血再灌注后,TPO组和缺血再灌注组大鼠缺血侧皮层可检测到凋亡细胞,且TPO组凋亡细胞数明显少于缺血再灌注组,差异有统计学意义(P0.05),而假手术组及正常组未检测到凋亡细胞;TPO组和缺血再灌注组缺血侧皮层Bcl-2阳性细胞数均高于假手术组及正常组,与缺血再灌注组相比,TPO组Bcl-2蛋白表达显著增高,差异有统计学意义(P0.05)。结论 TPO可抑制缺血再灌注损伤后缺血侧皮层的细胞凋亡,其机制可能是通过上调Bcl-2基因表达而实现。     

Hydrogen‐rich saline protects against liver injury in rats with obstructive jaundice

Background: Hydrogen selectively reduces levels of hydroxyl radicals and alleviates acute oxidative stress in many models. Hydrogen‐rich saline provides a high concentration of hydrogen that can be easily and safely applied. Aims: In this study, we investigated the effects of hydrogen‐rich saline on the prevention of liver injury induced by obstructive jaundice in rats. Methods: Male Sprague–Dawley rats (n=56) were divided randomly into four experimental groups: sham operated, bile duct ligation (BDL) plus saline treatment [5 ml/kg, intraperitoneal (i.p.)], BDL plus low‐dose hydrogen‐rich saline treatment (5 ml/kg, i.p.) and BDL plus high‐dose hydrogen‐rich saline treatment (10 ml/kg, i.p.). Results: The liver damage was evaluated microscopically 10 days after BDL. Serum alanine aminotransferase and aspartate aminotransferase levels, tissue malondialdehyde content, myeloperoxidase activity, tumour necrosis factor‐α, interleukin (IL)‐1β, IL‐6 and high‐mobility group box 1 levels were all increased significantly by BDL. Hydrogen‐rich saline reduced levels of these markers and relieved morphological liver injury. Additionally, hydrogen‐rich saline markedly increased the activities of anti‐oxidant enzymes superoxide dismutase and catalase and downregulated extracellular signal‐regulated protein kinase (ERK)1/2 activation. Conclusions: Hydrogen‐rich saline attenuates BDL‐induced liver damage, possibly by the reduction of inflammation and oxidative stress and the inhibition of the ERK1/2 pathway.     

非诺贝特对梗阻性黄疸大鼠肝细胞凋亡、肝糖原含量的影响

目的探讨非诺贝特对胆管结扎大鼠血清肝脏生化指标、肝细胞凋亡、肝糖原含量的影响。方法采用胆总管结扎手术制备胆汁淤积大鼠模型。48只雄性W istar大鼠随机分为4组（每组均为12只）：A组为对照组,B组为胆管结扎组,C组为胆管结扎＋非诺贝特组（30 mg.kg-1.d-1）,D组为胆管结扎＋非诺贝特（60 mg.kg-1.d-1）。术后7 d留取血标本及肝组织后处死,分别用全自动生化分析仪测定血清ALT、AST、ALP、GGT、TBA,TUNEL法检测肝细胞凋亡数目以及过碘酸希夫（PAS）染色法检测肝糖原含量。结果 B、C、D组大鼠血清ALT、AST、ALP、GGT、TBA显著高于A组（P〈0.001）,B组与C组大鼠血清ALT、AST、ALP、GGT、TBA差异无统计学意义,D组血清AST、ALP、GGT、TBA显著低于B、C组（P〈0.01）,而ALT在D与C组之间差异无统计学意义（P=0.021〉0.01）。所有胆管结扎组大鼠肝细胞凋亡显著高于对照组（P〈0.001）,C组肝细胞凋亡显著低于B组（P=0.007〈0.01）,D组肝细胞凋亡显著低于B组（P=0.000〈0.001）,D组肝细胞凋亡显著低于C组（P=0.000〈0.001）。PAS反应显示,非诺贝特可增加梗阻性黄疸大鼠肝糖原合成。结论非诺贝特可显著改善梗阻性黄疸大鼠血清肝脏生化指标、肝细胞凋亡以及增加肝细胞糖原合成。     

Effect of L-arginine on calcium in hepatic mitochondrion in rats with obstructive jaundice

BACKGROUND: There is much debate over the regulation of mitochondrial calcium overload and reducing the impairment of energy metabolism in hepatic cells. It has not been reported whether L-arginine (L-Arg) can affect hepatic mitochondrial calcium overload. This study was undertaken to investigate the protective effect of L-Arg on Ca2+ handling of hepatic mitochondrion in rats with obstructive jaundice and to clarify its possible mechanism. METHODS: Seventy-two male SD rats were randomly divided into 3 groups: sham operation+normal saline group (SO group), common bile duct ligation+normal saline group (BDL group), and common bile duct ligation+ L-Arg group (L-Arg group). The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and Ca2+ in rat hepatic mitochondrion were examined at the 7th, 14th and 21st day after operation. RESULTS: The Ca2+ and MDA levels of hepatic mitochondrion increased significantly but their SOD content decreased markedly at each time point in the BDL group. Except at the 21st day, the Ca2+ and MDA, contents of hepatic mitochondrion were significantly lower, and SOD concentrations were higher in the L-Arg group than those in the BDL group at the 7th and 14th day (P<0.01). CONCLUSION: L-Arg has a protective effect on mitochondrion in the early and mid stages of obstructive jaundice.     

生黄合剂对大鼠心肌缺血再灌注损伤的保护作用

目的观察生黄合剂对大鼠心肌缺血再灌注损伤(MIRI)的保护作用。方法将48只SD大鼠随机分为6组,即空白对照组、模型组、阳性药物组及生黄合剂低、中、高剂量组,每组8只,分别给药7 d后,建立MIRI模型。检测大鼠血清乳酸脱氢酶(LDH)及心肌丙二醛(MDA)和超氧化物歧化酶(SOD)的含量,用TUNEL法检测心肌细胞凋亡情况,并观察心肌组织形态学改变。结果与模型组比较,生黄合剂能降低大鼠LDH及MDA的含量,增加SOD活性,降低心肌细胞凋亡指数,改善心肌组织病理损害。结论生黄合剂对大鼠MIRI具有保护作用,其机制可能为通过抗自由基作用来抑制MIRI诱导的细胞凋亡。     

Effects of a selective thromboxane synthetase inhibitor (OKY-046) in patients with coronary artery disease during exercise

We studied the levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), platelet aggregability, beta-thromboglobulin and platelet factor 4 in 30 coronary artery disease (CAD) patients and 21 normal subjects during exercise. During treadmill exercise, 13 of 30 CAD patients reported chest pain. We administered a selective thromboxane synthetase inhibitor (OKY-046) for 2 weeks to 10 CAD patients with exercise-induced chest pain and studied its effects. At rest, the plasma TXB2 levels and platelet aggregation were significantly lower in normal subjects than in CAD patients, and there was no difference between CAD patients with and without exercise-induced chest pain. On treadmill testing, plasma TXB2 levels and platelet aggregation increased significantly only in the CAD patients with exercise-induced chest pain. Plasma 6-keto-PGF1 alpha levels in normal subjects were significantly higher than those in CAD patients both at rest and during exercise. After administration of OKY-046, mean exercise time increased significantly from 7.5 to 8.6 min (p less than 0.001). Plasma TXB2 level and platelet aggregation decreased significantly after OKY-046 administration both at rest and during exercise. These results suggest that a marked increase in TXA2, with only a minimal change in PGI2, during exercise may contribute to exercise-induced myocardial ischemia, and that OKY-046 is useful in the treatment of CAD patients.     

sCD40L在大鼠梗阻性黄疸肝损伤中的作用

目的探讨可溶性CD40L（soluble CD40L,sCD40L）在大鼠梗阻性黄疸肝损伤中的作用及其与肝损伤严重程度的相关性。方法 雄性SD大鼠18只,随机分为模型组、抗CD40L单克隆抗体（anti-CD40LmAb）组和假手术组各6只。模型组开腹后游离出胆总管双重结扎即关腹;单抗组同样方法造模后给予腹腔注射anti- CD40LmAb;假手术组仅予游离出胆总管即关腹。分别检测3组大鼠术后不同时间的血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBIL）、结合胆红素（DBIL）水平,以及肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）、sCD40L的浓度。结果 与模型组相比,单抗组血清ALT、AST、TNF-α、IL-8及sCD40L显著减低（P〈0．05）,而TBIL及DBIL水平差异无统计学意义（P〉0．05）。血清sCD40L与TNF-α、IL-8的水平呈正相关。结论 sCD40L可能参与梗阻性黄疸免疫肝损伤的启动阶段,阻断CD40／CD40L途径可能成为肝损伤治疗的有效方法之一,sCD40有望成为肝损伤程度的新指标。     

COX-2在对乙酰氨基酚致大鼠药物性肝损伤中的作用

目的探讨COX-2在对乙酰氨基酚致大鼠药物性肝损伤中的作用。方法选择40只SD大鼠随机分成对照组、塞来昔布对照组（A组）、对乙酰氨基酚组（B组）、对乙酰氨基酚＋塞来昔布组（C组）,每组10只。单次给药,24小时后采集血液测定ALT、AST、ALP、TBA等生化指标,之后处死大鼠,取其肝脏组织行病理学检查,应用免疫组织化学染色方法检测COX-2的表达。结果 B组肝损伤明显,C组肝损伤较B组严重。对照组大鼠肝脏组织未见COX-2的阳性表达;B组有7例COX-2表达呈阳性,阳性率为70.0%;C组仅有1例COX-2表达呈阳性,阳性率为11.1%。结论 COX-2在对乙酰氨基酚所致大鼠急性肝损伤肝组织中表达明显升高,阻断COX-2后,肝损伤加重。COX-2表达增高可能是机体对抗对乙酰氨基酚所致大鼠急性肝损伤的一种保护性机制。     

COX-2与氯丙嗪所致大鼠药物性肝损伤的研究

目的探讨COX-2在氯丙嗪所致大鼠药物性肝损伤中的作用。方法 40只SD大鼠随机分成空白对照组、西乐葆对照组、氯丙嗪组、氯丙嗪+西乐葆组,每组10只。单次给药,24 h后采集血液测定肝脏生化指标,之后处死大鼠,取肝脏组织做病理检查以及应用免疫组织化学染色方法检测COX-2的表达。结果氯丙嗪组肝损伤明显,氯丙嗪+西乐葆组肝损伤较氯丙嗪组严重。对照组大鼠肝脏组织未见COX-2的阳性表达;氯丙嗪组有8例COX-2呈阳性表达,阳性率为80%,氯丙嗪+西乐葆组有2例COX-2呈阳性表达,阳性率为20%。结论 COX-2在氯丙嗪所致大鼠急性肝损伤肝组织中表达明显升高,阻断COX-2后肝损伤加重,COX-2表达增高可能是机体对抗氯丙嗪所致大鼠急性肝损伤的一种保护性机制。     

肠内营养对梗阻性黄疸幼鼠肠屏障功能损害的保护作用

目的探讨肠内营养对梗阻性黄疸(OJ)幼鼠肠屏障损害的保护作用。方法48只Wistar幼鼠随机分为正常对照组,假手术组,OJ组和OJ+能全素组。OJ+能全素组给予肠内营养10d,总热量为610kJ/(kg.d),氮量1.0g/(kg.d)。实验结束时检测其血清内毒素(LPS)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平,取腹腔液做细菌培养。结果OJ组血清LPS、TNF-α、IL-6水平显著高于正常对照组和假手术组,LPS、TNF-α水平显著高于OJ+能全素组,OJ+能全素组上述指标与正常对照组和假手术组间差异无显著性。对照组细菌培养阳性1例(1/12)、假手术组2例(2/10)、OJ组7例(7/8)、OJ+能全素组4例(4/8),OJ组与对照组、假手术组相比,P<0.05,差异有显著性。结论肠内营养有助于减轻OJ幼鼠肠屏障功能的损害。     

Effects of aerosol administration of a thromboxane synthetase inhibitor (OKY-046) on bronchial responsiveness to acetylcholine in asthmatic subjects

Bronchial hyperresponsiveness is one of the major clinical features of bronchial asthma. We previously reported that oral administration of a selective thromboxane synthetase inhibitor, OKY-046, reduced bronchial hyperresponsiveness to acetylcholine in asthmatic subjects. In this study, the effect of aerosol administration of OKY-046 on bronchial hyperresponsiveness was evaluated in ten inpatients with intrinsic asthma. Acetylcholine inhalation tests were performed before and after four days of inhalation of OKY-046 (100 mg/day). The provocative concentration of acetylcholine producing a 20 percent fall in forced expiratory volume in 1 s (PC20-FEV1) and that causing a 35 percent fall in respiratory conductance (PC35-Grs) were measured as indexes of bronchial responsiveness. There was a significant increase in PC20-FEV1 (p less than 0.001) and PC35-Grs (p less than 0.02) after inhalation of OKY-046 from 0.79 (GSEM, 1.41) Mg/ml and 0.96 (GSEM, 1.35) mg/ml to 1.20 (GSEM, 1.41) mg/ml and 1.74 (GSEM, 1.32) mg/ml, respectively. There was no significant difference in forced vital capacity (FVC), FEV1, or respiratory resistance (Rrs) baseline values before and after inhalation of OKY-046. Platelet aggregation was not inhibited by the treatment in other five inpatients. Thus, prophylactic administration of aerosol OKY-046 may be available for treatment of asthma by reduction of bronchial hyperresponsiveness. Further studies are needed to determine the optimum dose.     

The effect of CV-4151, a selective inhibitor of thromboxane synthetase,on prostanoid formation and platelet aggregation in humans

Summary The pharmacokinetics and pharmacologic effects of a potent, selective inhibitor of thromboxane synthetase, CV-4151 [(E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid] on prostanoid formation and platelet aggregation were studied in 42 healthy male volunteers. The drug was well tolerated. After oral administration of 10 to 100 mg of CV-4151, peak plasma levels of 1–6 g/mL were reached in a dose-dependent mannor within 1 hour. Elimination followed first-order fashion with elimination half-life of about 1 hour. Serum levels of thromboxane B₂ reduced to 4% to 15% of control at 2 hours after drug ingestion dose-dependently. Serum levels of 6-Keto-prostaglandin F₁ increased to about four to six times basal levels. Platelet aggregation induced by collagen and arachidonate was inhibited in most eases. Such pharmacologic effects outlasted serum drug levels. In repeated administration, stable inhibition of serum thromboxane B₂ production and platelet aggregation in proportion to the enhancement of serum 6-keto-prostaglandin F₁ production was observed although no drug accumulation was found. These results indicate that CV-4151 may be suitable for clinical trials in cardiovascular diseases in which imbalance between thromboxane and prostacyclin may be involved in the pathogenesis.First Department of Medicine, Osaka University School of Medicine     

Zileuton,a 5-lipoxygenase inhibitor,increases production of thromboxane A2 and platelet aggregation in patients with asthma

Leukotrienes, generated from arachidonic acid via the lipoxygenase pathway, play an important role in the pathophysiology of asthma. Therefore, leukotriene inhibitors, such as Zileuton, are used in the treatment of asthma. However, thromboxanes, generated from arachidonic acid via the cyclooxygenase pathway, play an important role in platelet aggregation and thrombosis. Therefore, we studied whether Zileuton, by shifting arachidonic acid to the cyclooxygenase pathway, enhances thromboxane production and, hence, platelet aggregation. Blood samples were collected from 10 asthmatic patients before and 2 weeks after standard Zileuton treatment. Spontaneous platelet aggregation was measured in platelet-rich plasma. Platelet-rich plasma was also used to determine thromboxane B(2), a stable metabolite of thromboxane A(2), as the indirect measure of thromboxane A(2) because thromboxane A(2) is too unstable for assay. Baseline thromboxane B(2) and platelet aggregation values in the 10 asthmatic patients were normal. Treatment with Zileuton for 2 weeks significantly increased thromboxane B(2) levels from baseline levels of 267 +/- 54 microg/l to 389 +/- 62 microg/l after 2 weeks of treatment (P < 0.0002). Spontaneous platelet aggregation also increased significantly from baseline values of 4.2 +/- 2.4% to 6.8 +/- 2.8% after 2 weeks of treatment (P < 0.0001). These results establish that Zileuton, an effective drug for asthma, adversely affects in vitro platelet function. The findings suggest that this drug, and perhaps related agents also, may pose a thrombotic risk; clinical attention will be needed to address this possibility.     

缺血后处理对大鼠肝脏缺血再灌注损伤的保护作用

目的探讨缺血后处理对大鼠肝脏缺血再灌注损伤的保护作用。方法将75只SD大鼠随机分为假手术组、缺血再灌注组和缺血后处理组,建立大鼠肝脏局部缺血再灌注模型。检测大鼠血清、肝组织丙二醛（MDA）、超氧化物歧化酶（SOD）水平,并行肝组织病理学和超微结构检查及免疫组化法检测内源性一氧化氮合成酶（eNOS）的表达。结果与缺血再灌注组相比,缺血后处理组血清ALT和AST水平及肝组织MDA明显降低（P＜0．01）,而SOD水平则显著升高（P〈0．01）;肝组织病理损伤减轻,在再灌注7min时IPO组肝组织eNOS蛋白表达比IR组增强。结论缺血后处理可通过抑制再灌注后氧自由基的过量生成和再灌注损伤保护激酶通路,从而减轻肝细胞损伤。     

肝组织解偶联蛋白2在梗阻性黄疸及胆道再通实验大鼠模型中的表达及意义

目的研究梗阻性黄疸及胆道再通大鼠肝组织解偶联蛋白(UCP)2的表达及意义,探讨梗阻性黄疸对能量代谢障碍与氧化损伤的影响。方法 36只健康雄性大鼠随机分为6组,每组6只:假手术组(A组)、梗阻性黄疸1周组(B组)、梗阻性黄疸2周组(C组)、梗阻性黄疸1周再通1周组(D组)、梗阻性黄疸10 d再通1周组(E组)、梗阻性黄疸2周再通1周组(F组)。检测各组动物血清ALT、DBil、TBil水平;光镜下观察肝脏形态学改变;采用逆转录-聚合酶链反应(RT-PCR)法检测大鼠肝脏UCP-2mRNA的表达。结果胆道梗阻后,B、C 2组血清TBil、DBil、ALT水平较A组均升高(P值均0.05),C组升高较B组明显(P值均0.05)。光镜下可见B、C组肝细胞肿胀,炎性细胞浸润,汇管区伴胆管增生,C组出现典型的肝细胞片状坏死。B、C 2组肝组织UCP-2 mRNA表达较A组升高(P值均0.05),C组升高较B组明显(P0.05)。胆道再通组后,D、E、F 3组血清TBil、DBil、ALT水平呈不同程度下降。光镜下观察肝脏形态改变也明显趋于正常。D组肝细胞UCP-2 mRNA的表达高于B组(P0.05),F组的表达低于C组(P0.05),D组的表达低于E、F 2组(P值均0.05),E、F 2组差异无统计学意义(P0.05)。结论梗阻性黄疸时肝脏UCP-2 mRNA表达升高,随梗阻时间延长其升高趋势明显。解除梗阻时间早,则肝细胞再生活跃,UCP-2 mRNA表达暂时升高;解除梗阻时间迟,则肝组织损伤严重,再生缓慢,UCP-2 mRNA表达进行性下降,但仍高于正常。提示肝组织UCP-2 mRNA表达升高可能是梗阻性黄疸能量代谢紊乱的主要原因之一。