非诺贝特对胆管结扎大鼠血生化及肝组织病理学的影响

目的探讨非诺贝特对胆管结扎大鼠血清肝脏生化指标、肝组织丙二醛含量及组织病理学的影响。方法采用胆总管结扎手术制备胆汁淤积大鼠模型。24只雄性W istar大鼠随机分为两组（每组12只）：A组为胆管结扎＋生理盐水组,B组为胆管结扎＋非诺贝特组（30 mg/kg）。术后7 d留取血标本及肝组织后处死。采用全自动生化分析仪检测肝脏生化指标;分光光度计检测肝组织丙二醛含量;光镜下观察肝脏组织病理变化。结果两组血清肝脏生化指标无显著统计学意义;B组大鼠肝组织MDA含量显著低于A组（P=0.001）;B组肝脏坏死面积较A组显著减轻（P〈0.05）,汇管区小胆管数目较A组明显减少（P〈0.05）。结论非诺贝特可显著降低MDA含量,减少肝脏坏死面积以及小胆管增生。     

非诺贝特对慢性心力衰竭大鼠心肌能量代谢和心室重构的影响

目的研究非诺贝特对慢性心力衰竭(CHF)大鼠心肌能量代谢和心室重构的影响。方法健康雄性Wistar大鼠随机选为假手术组18只;采用腹主动脉缩窄术制备CHF、并成功存活的38只再随机分为对照组20只、非诺贝特组18只[非诺贝特150 mg/(kg·d)],干预10周。计算左心室心肌重构指数、胶原容积分数(CVF)、心肌线粒体损伤程度分级用Flameng评分,免疫印迹法测过氧化物酶体增殖物激活受体α(PPARα)、中链酰基辅酶A脱氢酶(MCAD)、肌型肉碱棕榈酰转移酶1(MCPT 1)蛋白表达,RT-PCR测PPARα、MCAD和MCPT-1mRNA表达。结果与假手术组比较,对照组及非诺贝特组左心室心肌重构指数、CVF和Flameng评分均升高(P<0.05);非诺贝特组左心室心肌重构指数高于对照组、CVF和Flameng评分低于对照组(P<0.05);与假手术组比较,对照组、非诺贝特组心肌PPARα、MCPT-1、MCAD蛋白和基因表达均下调(P<0.05);非诺贝特组表达较对照组上调(P<0.05)。结论非诺贝特通过增强脂肪酸氧化,减轻线粒体损伤,改善心室重构,减轻心肌纤维化。     

非诺贝特与大鼠急性缺血性损伤心肌的能量代谢

目的 探讨异丙肾上腺素(180)致大鼠急性心肌缺血性损伤中过氧化物酶体增殖物激活受体α(PPARα)配体非诺贝特与心肌能量代谢的关系.方法 健康纯系雄性Wistar大鼠90只随机分为3组,每组30只,即正常对照组、Iso损伤组(采用腹腔内注射Iso复制急性心肌缺血损伤的动物模型)和非诺贝特(FF)保护组(在预先给予FF的基础上复制Iso致急性心肌缺血损伤的动物模型).HE染色光镜下观察大鼠心肌形态学改变.检测脏器指数变化.铜显色法测定大鼠血清和心肌组织中游离脂肪酸含量.Western blot法测定大鼠心肌组织中PPARα的蛋白表达水平.结果 FF保护组和:Iso损伤组均可见心肌坏死,心脏指数显著高于对照组,血清和心肌组织中游离脂肪酸含量增高明显,同时PPARα在心肌组织中的表达水平也明显低于对照组.FF保护组与Iso损伤组比较,前者心肌病理改变轻,心肌坏死面积分别为(7.36±2.60)%和(10.00±3.00)%,组间比较P<0.01.FF保护组心脏指数低于Iso损伤组,分别为(4.03±0.10)和(4.32±0.11),组间比较P<0.01.FF保护组和Iso损伤组血清中游离脂肪酸含量分别为(736.53±70.30)、(939.53±69.51)μmol/L,心肌组织中游离脂肪酸含量分别为(116.28±14.03)、(140.59±19.34)μmol/L,前者均明显低于后者,组间比较P均<0.01.FF保护组心肌组织中PPARα表达水平高于Iso损伤组,分别为215.08±9.61和191.97±10.74,组间比较P<0.01.结论 在急性心肌缺血性损伤中,存在脂肪酸的利用障碍,即能量生成障碍,非诺贝特可以通过活化PPARα参与急性缺血性损伤心肌的能量代谢,对急性缺血性损伤心肌具有保护作用.     

非诺贝特微粒化胶囊联合辛伐他汀对混合型高脂血症的治疗

目的:观察非诺贝特微粒化胶囊联合辛伐他汀治疗混合型高脂血症的疗效和安全性。方法:冠心病及有高危因素的混合型高脂血症患者72例,分为两组:辛伐他汀组36例,口服辛伐他汀20mg,每日1次;非诺贝特微粒化胶囊加辛伐他汀组(联合治疗组)36例,在辛伐他汀基础上加服非诺贝特微粒化胶囊200mg,每日1次;两组疗程均为8周。观察治疗前后血脂变化和相关不良反应。结果:①两组治疗后血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)均有改善(P0.05～0.01),但联合治疗组治疗后LDL-C和TG改善情况优于辛伐他汀组(P0.05)。②联合治疗组TC、LDL-C、TG的达标率分别为58.3%、44.4%、50.0%,三项达标率为36.1%,明显高于辛伐他汀组的13.9%(P0.01)。③两组均没有出现严重不良反应。结论:非诺贝特微粒化胶囊联合辛伐他汀对混合型高脂血症的冠心病及有高危因素患者有较好调脂作用,值得在临床推广应用。     

微粒化非诺贝特调节老年代谢综合征患者血脂及尿酸代谢的研究

目的观察微粒化非诺贝特(非诺贝特)对老年代谢综合征患者血脂及尿酸代谢的影响,并探讨其潜在机制。方法入选131例老年代谢综合征患者,同时伴有高TG及高尿酸血症,每日顿服非诺贝特胶囊200 mg,疗程为4周。观察治疗前和治疗4周后主要血脂参数、血尿酸、24 h尿尿酸的变化及不良反应。结果非诺贝特治疗4周后:(1)患者血清TG下降最为显著,与基线比较下降49%,血清HDL-C水平升高18%,此外患者血清TC和LDL-C水平也有一定程度的下降(分别为11%和14%);(2)患者血尿酸水平由(472.5±74.8)μmol/L降至(325.0±82.1)μmol/L,下降幅度为31.2%。其中男性患者血尿酸水平下降32.6%,女性患者下降29.7%,差异均有统计学意义(P<0.01)。(3)患者24 h尿尿酸排泄明显增多,由(2 885.2±502.7)μmol/L增加至(3 701.7±768.2)μmol/L,排泄增加28.8%,其中男性24 h尿尿酸排泄高于女性(P<0.01)。结论非诺贝特具有同时改善老年代谢综合征患者的血脂及尿酸代谢异常的双重疗效,能明显促进尿尿酸排泄,且该作用与性别无关。     

非诺贝特对高胆固醇血症兔脂肪细胞摄取及降解氧化型低密度脂蛋白的影响

目的　观察兔脂肪细胞通过CD36摄取及降解氧化型低密度脂蛋白(OxLDL)的作用和非诺贝特对高胆固醇血症兔脂肪细胞OxLDL代谢的影响。方法　10只新西兰白兔给予高胆固醇饲料饲养8周后分为: (1)高胆固醇血症组:继续饲以高胆固醇饲料4周; (2)非诺贝特治疗组:在饲以高胆固醇饲料的基础上给予(30mg·kg-1·d-1 )非诺贝特4周。另选饲以普通饲料12周兔5只作为对照组。实验结束后,取皮下脂肪组织行脂肪细胞培养,放射配基法测定脂肪细胞对OxLDL的摄取及降解,RT PCR测定脂肪细胞CD36mRNA的表达。结果　喂饲胆固醇组血清总胆固醇、低密度脂蛋白胆固醇水平明显高于对照组(均P<0. 01),非诺贝特干预4周未对血脂产生影响,但能降低体重( -19%,P<0. 05 )。RT PCR示CD36在脂肪细胞分化过程中被诱导表达。放射配基实验发现兔脂肪细胞呈浓度依赖饱和型的摄取及降解OxLDL,细胞最大结合为2 065ng/mg细胞蛋白,解离常数(Kd)为4. 2mg/L;抗CD36抗体明显抑制脂肪细胞摄取(56% )及降解(54% )OxLDL;当125I OxLDL浓度为75mg/L时,对照组,高胆固醇组,非诺贝特治疗组脂肪细胞摄取125I OxLDL分别为3. 5, 2. 1, 2. 7μg/mg细胞蛋白, 降解125I OxLDL分别为2. 2, 1. 2,1. 7μg/mg细胞蛋白, 3组间差异有统计学意义(P<0. 05)。结论　CD36介导脂     

甘氨酸对梗阻性黄疸大鼠血清中TNF-α及肝细胞凋亡的影响

目的观察甘氨酸对梗阻性黄疽大鼠血清中肿瘤坏死因子（TNF-α）及肝细胞凋亡的影响。为临床应用甘氨酸治疗梗阻性黄疽提供理论依据。方法成年雄性大鼠54只，随机分为3组：假手术对照组（A组）；胆总管结扎组（B组）；（C）胆总管结扎＋甘氨酸组（C组）。每组术后再随机分设7、14、21d三个时相点采集标本，检测血清TNF—α和大鼠肝脏细胞凋亡情况。结果B组各时相点血清TNF-α含量及肝细胞凋亡指数（HAI）明显高于A组，且血清TNF-α含量及HAI呈正相关：C组各时相点血清TNF-α音量及HAI亦高于A组，但低于B组（P〈0．01）。结论甘氨酸能有效抑制大鼠梗阻性黄疽时血清TNF-α的产生及肝细胞的凋亡。     

bcl-2基因在阻塞性黄疸大鼠肝组织细胞凋亡中作用的研究

目的　探讨阻塞性黄疸大鼠肝组织损害的机制．方法　用末端脱氧核苷酸转移酶（ＴｄＴ） 介导的ｄＵＴＰ 缺口末端标记技术（ＴＵＮＥＬ） 和免疫组织化学方法检测阻塞性黄疸大鼠肝脏组织细胞凋亡状态及凋亡相关基因ｂｃｌ２ 的表达．结果　胆总管结扎后,随结扎时间的延长细胞凋亡增加,结扎１４ ｄ 后细胞凋亡达高峰,凋亡指数（ＡＩ） 达５８－２３ ±１－５８ ,各组ＡＩ差异有显著性意义（ Ｐ＜ ０－０５） ． 在阻塞性黄疸过程中,ｂｃｌ２ 蛋白表达越强,ＡＩ就越少．结论　ｂｃｌ２ 蛋白参与了阻塞性黄疸肝组织中细胞凋亡的调节,并在阻塞性黄疸肝损害的发生和发展中起重要作用．     

白介素-10对梗阻性黄疸大鼠肝组织转化生长因子β1表达和肝细胞凋亡的影响

目的:探讨白介素-10(IL-10)对梗阻性黄疸大鼠肝细胞凋亡的作用.方法:Wistar♂大鼠随机分为假手术(SO)组、梗阻性黄疸(OJ)组和IL-10组.OJ组和IL-10组结扎切断胆总管建立梗阻性黄疸模型,SO组仅游离胆总管.IL-10组术后第1天开始每天腹腔内注射IL-10(4μg/kg).实时荧光定量PCR法检测肝组织转化生长因子β1(TGF-β1)mRNA的水平,免疫组织化学法检测肝组织TGF-β1蛋白表达情况.末端脱氧核甘酸介导生物素标记(TUNEL)法检测大鼠肝细胞凋亡情况,并检测血清TBIL、DBIL、ALT和AST水平.结果:胆总管结扎术后3d,与SO组相比,OJ组大鼠血清转氨酶、肝组织TGF-β1表达水平及肝细胞凋亡率均明显升高(ALT:91.83U/L±21.47U/Lvs47.67U/L±12.79U/L;AST:208.67U/L±32.36U/Lvs75.17U/L±11.96U/L;TGF-β1mRNA:7.48±1.51vs1.21±0.79;TGF-β1蛋白:6.11%±1.11%vs1.26%±0.64%;凋亡:15.06%±1.17%vs3.94%±0.46%;均P<0....     

急性胆道感染诱发肝细胞凋亡的实验研究

目的研究急性胆道感染过程中是否存在肝细胞凋亡,并探讨肝细胞凋亡的可能机制。方法 30只实验大鼠适应喂养7 d后随机分为5组,每组6只,其中1组为对照组,余下4组为实验组。实验组通过胆总管注入大肠埃希菌,建立急性胆道感染模型,并于注入大肠埃希菌6、12、24及48 h后处死。对照组动物胆总管内注入1 ml生理盐水,6 h后处死。取各组肝组织,制作切片。HE染色,光镜下观察;Tunnel染色,计数调亡肝细胞,免疫组织化学试验检测bcl-2及Bax的表达,各组数据组间比较采用方差分析,进一步两两比较采用LSD-t检验以及Dunnett's T3法。结果对照组肝组织无明显病理变化,而实验组各组可见肝细胞凋亡改变。各实验组与对照组相比,Tunnel染色阳性表达差异均有统计学意义(P0.05),24及48 h组Tunnel染色阳性表达较12h组明显增加,差异有统计学意义(P0.05)。对照组与实验组间Bax表达差异有统计学意义(P0.05),在实验组间随着时间延长表现出增多的趋势,但差异无统计学意义(P0.05)。而Bcl-2在对照组和6及12 h实验组间差异无统计学意义(P0.05),但随着时间的延长,24及48 h组与12 h组比较差异有统计学意义(P0.05)。结论急性胆道感染后肝细胞在短时间内即会出现细胞凋亡,并且贯穿于急性胆道感染始终,基因层面表现为Bax表达增强,Bcl-2表达减弱。Bax与Bcl-2等凋亡相关基因表达的改变与肝细胞凋亡存在时间上的一致性,表明肝细胞凋亡可能与Bax与Bcl-2等基因有关。     

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.     

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.     

Effect of obstructive jaundice on hemodynamics in the liver and its clinical significance

BACKGROUND:Many diseases can cause obstructive jaundice and then lead to a series of pathologic disorders. Thus preoperative assessment of liver function is of utmost importance.Traditional assessment is to monitor related indicators of liver function,but it is invasive and needs to be performed repeatedly.Color Doppler flow imaging (CDFI)was used to monitor blood flow of the hepatic artery and portal vein,a non-invasive method which can be used repeatedly. METHODS:Twenty cases of obstructive jaundice were ...     

Preoperative transhepatic portal vein embolization for impaired residual hepatic function in patients with obstructive jaundice

Fifty patients with obstructive jaundice with biliary tract carcinoma who underwent percutaneous transhepatic portal vein embolization (PTPE) were studied to evaluate the clinical utility of PTPE in preparation for extensive liver resection. PTPE was performed 2–3 weeks before surgery, via the standard contralateral approach in the first seven patients and via the ipsilateral approach, devised by the authors, in the last 43 patients. The following portal branches in which embolization was planned were all successfully embolized: the right portal vein in 35 patients; the right portal vein plus the left medial portal branch in 6; the left portal vein and the right anterior portal branch in 3; the left portal vein in 2; the right anterior portal branch in 3; and the right posterior portal branch in 1. There were no procedure-related complications. Helical computed tomography demonstrated compensatory hypertrophy of the non-embolized segments. After PTPE, 35 of the 50 subjects underwent major hepatectomy with or without portal vein resection and/or pancreatoduodenectomy; the remaining 15 were found to have peritoneal dissemination or liver metastasis, and no resection was performed. Of the 35 hepatectomized patients, 3 died of posthepatectomy liver failure, and 1 patient died of pneumonia with pulmonary lymphangitis carcinomatosis; the other 31 patients were discharged in good condition. The hospital death rate was 11.8% (4/35), and mortality directly related to the surgery was 8.6% (3/35). PTPE appears to have the potential to increase the safety of extensive liver resection for patients with obstructive jaundice.     

Protective effects of thromboxane A2 synthetase inhibitor (OKY-046) on hepatic ischemia-reperfusion injury in rats with obstructive jaundice

The effects of OKY-046, a thromboxane A₂ synthetase inhibitor, on complete hepatic ischemia with obstructive jaundice were studied in male Wistar rats in vivo. The objective of this study was to investigate the influence of OKY-046 (i) on the hepatic microcirculation, as measured by tissue partial oxygen pressure (tPO₂), and (ii) on the release of interleukin-8 (IL-8) in hepatic tissue after reperfusion. Fourteen days after bile duct clamping, the rats were subjected to 30-min warm complete liver ischemia and then reperfusion. The rats were divided into three groups; one group received no treatment (controls, group C), one group received OKY-046 from 15 min before hepatic ischemia to the end of the experiment (group OKY), and the third group received gadolinium chloride (group Gd), injected intravenously to evaluate the contribution of the Kupffer cell to IL-8 production. Group OKY maintained significantly higher tPO₂ levels 5, 10, and 15 min after declamping compared to group C (P<0.05). The IL-8 level in liver tissue in group OKY was lower than that in group C, but the difference was not significant. Group Gd exhibited the lowest IL-8 level of the three groups (P < 0.05). These findings demonstrated that OKY-046 improved the hepatic microcirculation during the reperfusion period, influenced the Kupffer cells in terms of the avoidance of hypoxia, and depressed the concentration of IL-8 in liver tissue.     

Effect of salvia miltiorrhizae on apoptosis and NF-κB p65 expression in the liver of rats with severe acute pancreatitis or obstructive jaundice

Objective: To investigate the therapeutic effects and mechanism of salvia miltiorrhizae in the treatment of severe acute pancreatitis (SAP) or obstructive jaundice (OJ). Methods: SAP rat models were prepared and randomly divided into the model control group and treated group. The sham‐operated group was also set. At 3 h, 6 h and 12 h after operation, the mortality rate, the pathological changes in the liver, the contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, the expression levels of Bax and NF‐κB p65 proteins in the liver, and the apoptosis index of hepatic cells in SAP rats in each group were observed. On days 7, 14, 21 and 28 after operation, the above parameters and the contents of TBILI (total billirubin), DBILI (direct bilirubin) and r‐GT (r‐glutamyl transpeptidase) in serum in OJ rats were observed. Results: The contents of serum ALT (at 6 h and 12 h after operation) and AST (at 3 h and 12 h after operation) as well as the staining intensity of NF‐κB p65 protein (at 12 h after operation) in the liver of SAP rats in the treated group were significantly lower than those in model control group (all P < 0.01). The pathological severity scores (on 21 d and 28 d after operation) in the liver, the contents of serum ALT (on 14 d and 21 d after operation), AST (on 21 d after operation), TBILI (on 21 d and 28 d after operation), DBILI (on 28 d after operation) and r‐GT (on 21 d after operation), and the apoptosis index of hepatic cells in OJ rats in treated group were significantly lower than those in model control group (all P < 0.05). The positive rates of Bax protein (on 28 d after operation) in treated group was significantly lower than model control group (P < 0.05). Conclusions: Salvia miltiorrhizae is able to improve the liver function of SAP or OJ rats, suppress the expression of NF‐κB p65 protein in the liver of SAP rats, and inhibit apoptosis in OJ rats, thereby showing some protective effects on the liver of SAP or OJ rats.     

108例阻塞性黄疸的超声诊断分析

目的 探讨超声在阻塞性黄疸诊断中的价值.方法 对我院2004-2007年收治并手术的108例阻塞性黄疸患者的超声声像图进行回顾性分析和总结.结果 阻塞性黄疸超声诊断与手术病理结果符合102例(94.4%),其中胆管结石65例,诊断符合率100%;胆管狭窄2例,诊断符合率66.6%;胰腺炎1例,诊断符合率50.0%;胆囊炎(向后压迫)3例,诊断符合率100%;胰头癌14例,诊断符合率87.5%;壶腹癌11例,诊断符合率91.7%;胆管癌6例,诊断符合率85.7%.结论 超声诊断阻塞性黄疸与手术病理结果符合率高,可作为阻塞性黄疸检查的首选方法,结合临床可提高诊断率.     

以黄疸为特征的原发性肝淀粉样变性1例报告

淀粉样变性是由不溶性淀粉样蛋白沉积在组织器官中引起的一类进行性、预后不良的疾病,主要可分为原发性（淀粉样物质为免疫球蛋白的轻链,AL型） 和继发性（淀粉样物质为淀粉A 蛋白,AA 型）.AL 型常累及肝、肾、脾、心脏、胃肠及皮肤等多个组织器官,以往的尸解发现95%的原发性淀粉样变性患者都有肝脏淀粉样物质沉积.