妊娠期肝内胆汁淤积症胆汁酸、肝酶指标对妊娠结局的影响

目的探讨妊娠期肝内胆汁淤积症（ICP）不同胆汁酸和肝酶水平对围生儿妊娠结局的影响。方法依据胆汁酸和肝酶水平将本院的163例ICP患者分为轻度组、中度组和高度组,分析3组的分娩方式、常规指标（新生儿体重、胎龄、Apgar评分及并发症）和妊娠结局,并与正常孕妇作对照。结果ICP中度组和重度组的剖宫产率均高于正常孕妇组和轻度组（P〈0．01）,常规指标差于其余两组,且新生儿死亡、小于胎龄儿、早产和低体重的发生率均高于其余两组（P〈0．05）;除重度组的常规指标差于中度组外,其余均差异无统计学意义;除1minApgar评分外。轻度组的常规指标、分娩方式和妊娠结局均与正常孕妇组差异无统计学意义（P〈0．05）。结论中重度奸娠期肝内胆汁淤积症行剖宫产的机率较大．新生儿常规指标及妊娠结局较差．应加强预防及治疗。     

妊娠期肝内胆汁淤积症血清胆汁酸与肝功能检测的临床意义

目的探讨妊娠期肝内胆汁淤积症(ICP)患者血清总胆汁酸(TBA)和肝功能的改变特点,分析其临床意义。方法收集50例ICP患者和50名正常妊娠女子空腹血清,测定血清TBA含量,同时检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT),观察ICP患者血清TBA和肝功能异常与母儿并发症及妊娠结局的关系。结果 ICP组血清TBA(73.9±13.6)μmmol/L,显著高于对照组(7.8±2.1)μmol/L,(P<0.01);ICP组血清ALT和AST及GGT分别为(98.5±6.8)U/L和(84.2±5.6)U/L及(143.9±14.7)U/L,显著高于对照组(32.5±5.1)U/L和(25.3±5.2)U/L及(35.1±4.5)U/L,(P均<0.01)。ICP患者肝功能及血清TBA值异常,可使孕妇自觉症状加重,倒置胎儿宫内窘迫,胎儿宫内发育迟缓,早产,产时并发症等。结论血清TBA和肝功能是敏感的指标,反映了病情的严重性,对ICP的临床诊断,疗效判断及病情发展有重要参考价值,可进一步提高了我们对ICP的认识。     

妊娠期肝内胆汁淤积症胆汁酸对新生儿并发症及预后的影响

目的：探讨妊娠期肝内胆汁淤积症胆汁酸对新生儿并发症及预后的影响。方法选取2012年1月~2014年1月入院治疗的68例妊娠期肝内胆汁淤积症孕妇为肝内胆汁淤积症组,同期正常孕妇68例为健康对照组。观察比较两组孕妇胆汁酸、丙氨酸氨基转移酶,新生儿的胎龄、出生质量和宫内窘迫的发生率。结果肝内胆汁淤积症组孕妇的胆汁酸和丙氨酸氨基转移酶水平均高于健康对照组,差异有统计学意义(t=13.0045,P=0.0000;t=7.2784,P=0.0000);肝内胆汁淤积症组新生儿的胎龄和出生质量均明显低于健康对照组,差异有统计学意义(t=21.1026,P=0.0000;t=16.6681,P=0.0000);肝内胆汁淤积症组宫内窘迫发生率高于健康对照组,差异有统计学意义(字2=4.1676,P=0.0412)。结论妊娠期肝内胆汁淤积症孕妇的胆汁酸水平显著升高,可导致宫内窘迫发生率升高,新生儿胎龄短、出生质量低,整体预后效果不佳。     

Changes of acid phosphatase and alkaline phosphatase activities in the femur of rats dosed orally with stannous chloride

Acid phosphatase activity in femur of intact but not of thyroparathyroid-ectomized male rats was significantly increased by the oral administration of stannous chloride (3.0 mg Sn²⁺/100 g body weight, 6 times at 12-h intervals). Femoral alkaline phosphatase activity was markedly decreased in the intact rats, but was not significantly reduced in the thyroparathyroidectomized rats. It is suggested that the increase in femoral acid phosphatase activity is induced by parathyroid hormone (PTH).     

Exogenous alkaline phosphatase treatment complements endogenous enzyme protection in colonic inflammation and reduces bacterial translocation in rats

Alkaline phosphatase (AP) inactivates bacterial lipopolysaccharide and may therefore be protective. The small intestine and colon express intestinal (IAP) and tissue nonspecific enzyme (TNAP), respectively. The aim of this study was to assess the therapeutic potential of exogenous AP and its complementarity with endogenous enzyme protection in the intestine, as evidenced recently. IAP was given to rats by the oral or intrarectal route (700U/kgday). Oral budesonide (1mg/kgday) was used as a reference treatment. Treatment with intrarectal AP resulted in a 54.5% and 38.0% lower colonic weight and damage score, respectively, and an almost complete normalization of the expression of S100A8, LCN2 and IL-1β (p<0.05). Oral AP was less efficacious, while budesonide had a more pronounced effect on most parameters. Both oral and intrarectal AP counteracted bacterial translocation effectively (78 and 100%, respectively, p<0.05 for the latter), while budesonide failed to exert a positive effect. AP activity was increased in the feces of TNBS colitic animals, associated with augmented sensitivity to the inhibitor levamisole, suggesting enhanced luminal release of this enzyme. This was also observed in the mouse lymphocyte transfer model of chronic colitis. In a separate time course study, TNAP was shown to increase 2-3 days after colitis induction, while dextran sulfate sodium was a much weaker inducer of this isoform. We conclude that exogenous AP exerts beneficial effects on experimental colitis, which includes protection against bacterial translocation. AP of the tissue-nonspecific isoform is shed in higher amounts to the intestinal lumen in experimental colitis, possibly aiding in intestinal protection.     

金胆片对大鼠肝内胆汁淤积模型的预防作用

目的:探讨金胆片对α-萘异硫氰酸酯(ANIT)诱导大鼠肝内胆汁淤积的预防作用。方法:Wister大鼠随机分为正常对照组、模型对照组、阳性对照组、金胆片低、高剂量组。灌胃给予金胆片4 d后,采用ANIT诱导大鼠肝内胆汁淤积模型。造模后4 d测定大鼠胆汁流量和流速,以及血清总胆红素(TBIL)、直接胆红素(DBIL)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和总胆汁酸(TBA)等生化指标的含量。取大鼠肝组织进行切片,HE染色,显微观察病理学改变。结果:金胆片可以显著增加肝内胆汁淤积大鼠的胆汁流量和流速,降低血清TBIL、DBIL、ALT、AST和TBA水平(P<0.05);并可显著缓解胆汁淤积状态下的肝细胞损伤。结论:金胆片对肝内胆汁淤积具有一定的预防作用,具有较好的临床价值。     

Influence of ascorbic acid on acid and alkaline phosphatase activities in some metabolically active tissues of aspirin treated rats

ACP and ALP activities in plasma were increased in aspirin treated groups for a period of seven days. Ascorbic acid supplemented groups showed no significant change in plasma ACP activity, but a significant change in ALP activity was found. ACP and ALP activities in liver and kidney were decreased significantly in aspirin treated animals. ACP activities in liver and kidney in ascorbic acid supplemented groups showed no significant changes. No significant alteration of ALP activity in liver was found in ascorbic acid supplemented group but a significant changes was observed in kidney. Supplementation of ascorbic acid in high doses to rats fed aspirin can restore enzyme activities almost to the normal level.     

The optimum pH of serum alkaline phosphatase after induced cholestasis in the male rat, mouse and rabbit

The optimum pH of serum alkaline phosphatase (alk. P., EC 3.1.3.1) was investigated in adult male rats, mice and rabbits after fasting or after the induction of cholestasis by a single oral dose of 200 mg/kg alpha-naphthylisothiocyanate (ANIT). The nature of serum alk.P. was also studied with the inhibitory effects of three L-amino acids (L-phenylalanine, L-homoarginine and L-cystine) and by electrophoresis. In the rat, fasting as well as ANIT-treatment shifted the optimum pH of alk.P. from 9.4 to 10.0 due to a decrease in intestinal isoenzymes or due to newly appeared liver isoenzymes, while no shifting occurred in mouse and rabbit.     

茵栀黄口服液对雌激素诱导的妊娠期大鼠肝内胆汁淤积的影响

目的:探讨茵栀黄口服液对雌激素诱导的妊娠期大鼠肝内胆汁淤积的影响。方法:将妊娠12 d的SD大鼠随机分为正常对照组、模型对照组、阳性对照组和茵栀黄口服液高、中、低剂量组。肌内注射苯甲酸雌二醇(EB),1 h后灌胃给药,1周后测定妊娠大鼠胆汁流量和血清总胆汁酸(TBA)、总胆红素(TBIL)、碱性磷酸酶(AKP)、雌激素(E2)水平。结果:茵栀黄口服液可以增加EB诱导的肝内胆汁淤积妊娠大鼠的胆汁流量,显著降低血清中TBA、TBIL、AKP和E2水平。结论:茵栀黄口服液可以改善EB诱导的妊娠期大鼠肝内胆汁淤积状况,其作用可能是通过降低大鼠体内的雌激素水平而产生。     

Hepatic extraction of bile acids in rats

The hepatic extraction ratio (E_h) of five common bile acids was determined by comparison of the area under the plasma concentration time curve (AUC) after administration into the femoral and portal veins of rats. Taurocholic acid (TCA), glycocholic acid (GCA), cholic acid (CA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) were studied. Using equimolar doses of the bile acids (9.3 μmoles), the effects of both conjugation and the number and position of hydroxyl groups on E_h were compared. TCA had the highest E_h (about 80 per cent) followed in order by GCA (65 per cent), CA (55 per cent) and CDCA (55 per cent), with DCA exhibiting the lowest E_h (40 per cent). This suggests that conjugation has a more important effect on hepatic extraction of bile acids than the number of hydroxyl groups.     

被动吸烟对妊娠肝内胆汁淤积症的影响

目的　探讨被动吸烟与妊娠肝内胆汁淤积症 (ICP)之间的关系。方法　随机选取妊娠后发生ICP孕妇 5 0例 ,其中被动吸烟组孕妇 2 1例 (被动吸烟 ICP组 )和无吸烟及被动吸烟组孕妇 2 9例 (正常 ICP组 )。对瘙痒发生时间 <2 8周 ,血清胆酸 >正常值 5倍 ,血清胆红素平均值以及早产、宫内窘迫发生率和新生儿体重 ,两组进行比较。结果　被动吸烟 ICP组孕妇瘙痒发生时间 <2 8周的发生率及血清胆红素平均值较正常 ICP组明显升高 (P<0 .0 5 ) ;血清胆酸 (CG)的变化两组无差异 (P>0 .0 5 ) ;宫内窘迫发生率被动吸烟 ICP组明显高于正常ICP组 (P<0 .0 5 ) ;新生儿体重被动吸烟 ICP组明显低于正常 ICP组 (P<0 .0 5 ) ;早产发生率两组无差异 (P>0 .0 5 )。结论　被动吸烟导致 ICP孕妇临床症状加重 ,新生儿宫内窘迫发生率和胎儿宫内发育迟缓增加。这些不良后果可能与被动吸烟引起 ICP孕妇血清 NO含量进一步减少也有关系。     

妊娠期肝内胆汁淤积症的处理与妊娠结局

目的:探讨妊娠期肝内胆汁淤积症的处理以及对妊娠结局的影响,以防范医疗风险.方法:总结分析典型病例的诊治经过与妊娠结局,并复习文献.结果:例1在引产待产过程中胎儿死亡,再次妊娠时发病早、病情重,药物及综合治疗可延长孕龄,仍发生早产、胎膜早破和胎粪污染,需及时剖腹产.结论:本病医疗风险极大,无有效治疗方法来控制病情发展,掌握终止妊娠的时机和方法最关键.母亲预后好,围产儿发病率和死亡率高.     

Genetic variations of bile salt transporters as predisposing factors for drug-induced cholestasis, intrahepatic cholestasis of pregnancy and therapeutic response of viral hepatitis

INTRODUCTION: Drug-induced cholestasis, intrahepatic cholestasis of pregnancy and viral hepatitis are acquired forms of liver disease. Cholestasis is a pathophysiologic state with impaired bile formation and subsequent accumulation of bile salts in hepatocytes. The bile salt export pump (BSEP) (ABCB11) is the key export system for bile salts from hepatocytes. AREAS COVERED: This article provides an introduction into the physiology of bile formation followed by a summary of the current knowledge on the key bile salt transporters, namely, the sodium-taurocholate co-transporting polypeptide NTCP, the organic anion transporting polypeptides (OATPs), BSEP and the multi-drug resistance protein 3. The pathophysiologic consequences of altered functions of these transporters, with an emphasis on molecular and genetic aspects, are then discussed. EXPERT OPINION: Knowledge of the role of hepatocellullar transporters, especially BSEP, in acquired cholestasis is continuously increasing. A common variant of BSEP (p.V444A) is now a well-established susceptibility factor for acquired cholestasis and recent evidence suggests that the same variant also influences the therapeutic response and disease progression of viral hepatitis C. Studies in large independent cohorts are now needed to confirm the relevance of p.V444A. Genome-wide association studies should lead to the identification of additional genetic factors underlying cholestatic liver disease.     

血清总胆汁酸测定诊断妊娠肝内胆汁淤积症的临床意义分析

目的：分析血清总胆汁酸（TBA）测定诊断妊娠肝内胆汁淤积症（ICP）的临床意义。方法选取本院收治的42例ICP孕妇作为观察组,另选择同期体检的40例健康孕妇为对照组,分别检测两组孕妇的血清TBA、ALT、AST、TBiL水平,并对比分析两组孕妇血清TBA、ALT、AST、TBiL指标水平和异常率及观察组孕妇不同孕周条件下血清TBA水平。结果观察组孕妇血清TBA、ALT、AST水平均高于对照组（P〈0.05）,且相较于ALT、AST,血清TBA对应的P值最小。观察组孕妇血清TBA、ALT、AST异常率均高于对照组（P〈0.05）,且相较于ALT、AST,血清TBA对应的P值最小。观察组孕妇血清TBA指标异常率高于ALT、AST异常率（P〈0.05）。随着妊娠肝内胆汁淤积症孕妇孕期的进展,血清TBA水平逐渐升高（P〈0.05）。结论相较于ALT、AST,血清TBA测定诊断ICP的灵敏性和特异性更好,可作为ICP患者常规检测项目之一。     

川芎嗪对妊娠期肝内胆汁淤积的疗效观察

目的探讨川芎嗪对妊娠期肝内胆汁淤积症（ICP）的治疗作用。方法将60例ICP患者随机分为对照组和观察组,对照组采用熊去氧胆酸等常规治疗,观察组在常规治疗基础上加用川芎嗪,对照组2例失访,最终纳入统计的为对照组28例,观察组30例,观察两组患者瘙痒和血液生化的改善情况。结果观察组瘙痒和血液生化的改善优于对照组,两组差异有统计学意义（P〈0.05或P〈0.01）。结论川芎嗪适合于ICP的治疗。     

妊娠期肝内胆汁淤积症对妊娠结局的影响

目的 探讨妊娠期肝内胆汁淤积症对妊娠结局的影响.方法 70例确诊为肝内胆汁淤积症的妊娠期妇女设为研究组,选取同一时期70例健康妊娠妇女设为对照组.对两组妊娠期妇女的妊娠结局进行比较.结果 (1)研究组孕产妇血清胆汁酸、谷氨酸氨基转移酶、天冬氨酸氨基转移酶水平分别为(65.61±13.5) μmol/L、(134.31±24.7) U/L、(97.35±21.54) U/L,均高于对照组的(3.34±0.41) μmol/L、(36.16±4.15) U/L、(23.34±4.45) U/L,差异具有统计学意义(P＜0.01);(2)研究组孕产妇妊娠期高血压疾病发病率为21.42％,胎膜早破发生率为17.14％,产后出血发生率为15.71％,显著高于对照组的7.14％、5.71％、4.29％,差异具有统计学意义(P＜0.05);(3)研究组新生儿窒息发生率为27.14％,羊水污染发生率为35.71％,宫内窘迫发生率为22.86％,低体重儿所占比例为30.00％,与对照组相比,均显著升高,差异具有统计学意义(P＜0.01).结论 妊娠期肝内胆汁淤积症可以增加围生期并发症的发生率,严重影响胎儿的预后,加强对妊娠期肝内胆汁淤积症的监测具有重要临床意义.     

A novel protein with alkaline phosphatase and protease inhibitor activities in Streptomyces hiroshimensis

A novel alkaline phosphatase (S-ALP) was found in the culture filtrate of Streptomyces hiroshimensis IFO 12785. Purification was achieved on Sephadex G-75 column, palmitoylated gauze column, and Superdex 75 HR column chromatographies. The molecular weight of S-ALP was estimated to be 14200 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The isoelectric point is 9.2. S-ALP had maximum enzyme activity at pH 9.5. S-ALP efficiently catalyzed both p-nitrophenyl phosphate and p-nitrophenyl phosphorylcholine substrates, particularly the latter. The N-terminal amino acid sequence (25 residues) of S-ALP was 60 to 72% identical to that of Streptomyces subtilisin inhibitor-like proteins. S-ALP exhibited trypsin inhibition in addition to a strong inhibition of subtilisin.     

不同程度妊娠期肝内胆汁淤积症对胎儿及新生儿的影响研究

目的：探讨不同程度妊娠期肝内胆汁淤积症（ICP）对胎儿及新生儿的影响。方法：回顾性分析上述产妇围生期临床资料,比较正常产妇与不同程度ICP患者肝功能、胎儿宫内窘迫的发生、羊水污染状况、新生儿状况及新生儿并发症等。结果：无论轻度还是重度ICP组患者体内TBI水平均明显高于正常对照组,胎儿窘迫、羊水污染、新生儿窒息、新生儿低体重以及新生儿多种并发症的发生率明显升高,差异有统计学意义（P〈0.05）,且与ICP患者的轻重程度呈正相关。结论：在妊娠晚期评估ICP患者病情严重程度,对及时治疗和选择安全有效的妊娠方式,减少ICP患者及新生儿不良事件的发生具有明确的临床意义。     

碱性磷酸酶和骨碱性磷酸酶在儿童缺钙中的临床应用

目的 探讨碱性磷酸酶和骨碱性磷酸酶在儿童缺钙中的临床应用.方法 回顾性分析我院收治的74儿童缺钙患者临床资料,将其设为试验组.将同期我院收治的68例健康儿童者作为对照组.测定及分析两组血钙、碱性磷酸酶及骨碱性磷酸酶水平的差异.结果 试验组患者血钙低发生率为58.1％(43/74),高于对照组的17.6％(12/68),差异有统计学意义(x2=24.45,P＜0.05).血钙低者碱性磷酸酶及骨碱性磷酸酶显著高于血钙正常者,差异有统计学意义(P＜0.05).结论 血钙、碱性磷酸酶及骨碱性磷酸酶均可反映儿童缺钙情况,但血钙水平并不能完全反映缺钙与否,低血钙者的碱性磷酸酶、骨碱性磷酸酶较血钙正常者显著升高,其对评价患者是否缺钙具有较高的临床价值,尤其对血钙正常者,值得临床选择.