口服钩藤总碱对高血压大鼠的肝毒性

<正>中药钩藤的主要有效部位是生物碱。研究表明[1],钩藤总碱有抗高血压作用。考虑到抗高血压治疗需长期用药并且钩藤总碱主要经肝代谢,实验考察了钩藤总碱对肝脏和肝功能的影响。1材料自发性高血压大鼠(SHR)40只,20周龄,♂,无创尾动脉测压收缩压不低于20.0 kPa。天麻钩藤饮颗粒(成都九芝堂金鼎药业有限公司,批号090418)。钩藤总碱(第88医院制剂室提取,总生物碱含量约95%,其中,钩藤碱含量11.9%,     

转氨酶指数判断抗结核药物肝毒性作用的临床意义探讨

报告57例肺结核在抗痨过程中出现血清转氨酶升高的住院病人。采用转氨酶指数(TI)作为肝功能损害程度的生化指标,探讨肺结核病人在使用含异烟肼和利福平的抗痨过程中出现肝功能损害时,TI对进一步治疗方案确定的指导作用。1 资料与方法1.1 一般材料 57例临床资料为1995年3月至1998年5月住院的肺结核病人,其中Ⅰ型7例,Ⅲ型38例,Ⅳ型12例。男45例,女12例;年龄16～74岁,平均43.8岁。有明显肝功能损害、乙肝两对半阳性或使用其他潜在性肝损害药     

纳美芬与门冬氨酸鸟氨酸联合治疗肝性脑病的临床疗效

目的观察纳美芬与门冬氨酸鸟氨酸联合治疗肝性脑病的疗效。方法纳入84例肝性脑病患者,随机分为对照组(门冬氨酸鸟氨酸20 g)和联合治疗组(纳美芬0.1 mg和门冬氨酸鸟氨酸10 g),均n=42。观察患者治疗前后的清醒时间、肝功能、血氨等变化。结果对照组和联合治疗组总有效率分别为54.8%和92.9%,两组比较有显著差异(P<0.05)。联合治疗组患者的清醒时间为(6.48±3.69)h,与对照组(27.11±8.21)h相比显著减少(P<0.05)。与对照组相比,联合治疗组患者的丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素和血氨水平均明显降低(P<0.05)。结论纳美芬与门冬氨酸鸟氨酸联用治疗肝性脑病疗效好,优于单用门冬氨酸鸟氨酸。     

垃圾渗滤液所致大鼠肝毒性研究

垃圾填埋过程中产生的垃圾渗滤液如处理不当将造成地下水污染,给附近居民的健康带来隐患[1].渗滤液的成份非常复杂,其中一些化合物含量虽然低,却有很强的毒性和"三致"效应[2-4].     

注射HBsAg-SCT质粒的HBV转基因小鼠血清转氨酶的检测分析

目的研究注射HBsAg-SCT质粒的HBV转基因小鼠血清中转氨酶水平的变化。方法选取遗传背景相同的HBsAg阴性正常鼠30只作为正常对照组,HBV转基因鼠30只为实验1组,注射HBsAg-SCT质粒的HBV转基因小鼠30只为实验2组。采集各组小鼠在8周龄时的血液,用全自动的生化分析仪检测小鼠血清丙氨酸转氨酶和天冬氨酸转氨酶水平。结果实验1组(HBV转基因小鼠未注射HBsAg-SCT质粒组)和实验2组(HBV转基因小鼠注射HBsAg-SCT质粒组)小鼠的血清丙氨酸转氨酶、天冬氨酸转氨酶与正常对照组比较,均显著升高(P<0.01);实验1组小鼠的血清丙氨酸转氨酶、天冬氨酸转氨酶与实验2组比较,无明显差异(P>0.05)。结论注射HBsAg-SCT质粒的HBV转基因小鼠血清转氨酶水平明显高于正常小鼠;但与未注射HBsAg-SCT质粒HBV转基因小鼠无明显差异。     

柴胡总皂苷肝毒性肝纤维化损伤机制研究

目的探讨柴胡总皂苷肝毒性损伤与肝脏纤维化的相关性,为阐明其肝毒性机制提供依据。方法大鼠连续15天灌胃高、中、低不同剂量,按等生药量计算,高、中、低剂量分别为300、150、50 mg.kg-1,末次药后取血和肝组织,检测血清及肝组织匀浆中羟脯氨酸含量的变化;并作大鼠肝脏组织Masson’s病理学检查。结果 15天给药结束后药物组大鼠血清和肝组织羟脯氨酸含量均明显升高,随给药剂量增加羟脯氨酸含量升高幅度增大,与正常对照组比较呈现不同程度的显著性差异;马松染色肝组织病理改变可见胶原纤维延伸明显,并互相连接包绕整个肝小叶,导致正常肝小叶结构破坏,假小叶形成。药物高、中、低剂量之间的肝毒性损伤程度有一定的剂量依赖关系,与空白组相比有明显差异。结论连续15天灌服一定剂量的柴胡总皂苷可导致大鼠明显的肝纤维化,柴胡总皂苷是其肝毒性主要物质基础,为柴胡总皂苷的肝毒性评价提供了实验依据,为其毒性预警和临床安全应用提供对策及科学依据。     

肝毒性生物标志物研究进展

药物肝毒性是医药界关注的重要问题。及时准确地评价药物的肝毒性,寻找特异性强、灵敏度高的肝毒性生物标志物对新药研发及保证临床用药安全具有重要意义。针对传统的肝毒性生物标志物（包括谷氨酸氨基转移酶、天冬氨酸氨基转移酶、谷氨酸脱氢酶等）,以及新发现的生物标志物（血清F蛋白、嘌呤核苷磷酸酶、激肽原对氧磷酶）进行综述,为药物肝毒性的研究及防治提供参考。     

脂肪肝诊断中转氨酶水平检验的临床价值分析

目的探讨转氨酶水平检验在脂肪肝诊断中的临床价值。方法选择2013年7月至2015年8月收治并确诊的75例脂肪肝患者作为观察组,选择75例同期健康体检者作为对照组,两组均采用全自动生化分析仪及配套试剂检测天冬氨酸转氨酶(AST)及丙氨酸转氨酶(ALT),对比转氨酶检测值及升高率。结果观察组AST、ALT检测水平明显高于对照组(65.36±5.30vs31.50±2.21,78.42±5.67vs35.14±2.48),且AST、ALT升高率也明显高于对照组(68.0%vs2.7%,58.7%vs4.0%),P<0.05,差异存在显著统计学意义。结论转氨酶水平检验能够为脂肪肝诊断提供重要的参考依据,临床价值较高。     

三七皂苷促进急性肝功能衰竭大鼠肝脏修复的实验研究

目的 探讨三七皂苷（PNS）对急性肝功能衰竭（AHF）大鼠肝脏修复的促进作用.方法 选择雄性Wistar大鼠262只,随机分为3组,其中模型组150只,PNS组100只,正常对照组12只.采用四氯化碳腹腔注射法（四氯化碳与橄榄油的体积比为1∶1）建立AHF模型,分别于造模后第1,3,7,14天共4个时间点开腹,采取下腔静脉血标本查血清丙氨酸氨基转移酶（ALT）及肝组织标本进行病理检查.结果 与模型组比较,PNS组动物肝脏组织损伤程度明显较轻,动物总死亡率明显较低（P＜0.05）,损伤后血清ALT水平恢复较快（P＜0.01）.结论 PNS可减轻AHF急性期肝损伤,降低死亡率,促进肝细胞的增生修复及肝组织的重构.     

Histological analysis of 70-nm silica particles-induced chronic toxicity in mice

Nano-sized silica is a promising material for disease diagnosis, cosmetics and drugs. For the successful application of nano-sized material in bioscience, evaluation of nano-sized material toxicity is important. We previously found that nano-sized silica particles with a diameter of 70 nm showed acute liver failure in mice. Here, we performed histological analysis of major organs such as the liver, spleen, lung, kidney, brain and heart in mice, chronically injected with 70-nm silica particles for 4 weeks. Histological analysis revealed hepatic microgranulation and splenic megakaryocyte accumulation in these 70-nm silica particles treated mice, while the kidney, lung, brain and heart remained unaffected. Thus, liver and spleen appear to be the major target organs for toxicity by the chronic administration of the 70-nm silica particles.     

血清总胆汁酸和ALT测定在肝病中变化的研究

目的 探讨急性、慢性肝炎血清总胆汁酸测定的诊断价值。方法 回顾性地分析经临床和实验室诊断证实为急性肝炎患者55例、慢性肝炎患者56例,同时选取65例健康人作为对照组,对其血清总胆汁酸含量进行了测定,并与其血清丙氨酸氨基转移酶测定结果进行比较分析。结果 对照组、急性肝炎、慢性肝炎组血清总胆汁酸(umol/L)、丙氨酸氨基转移酶(U/L)测定结果(x±s)分别是:(4.10±2.32)、(18.75±13.89),(39.01±11.43)、(295.09±160.81),(17.60±7.52)、(81.21±55.26);急性肝炎、慢性肝炎患者血清总胆汁酸、丙氨酸氨基转移酶与健康人对照组比较有显著性差异(P<0.001)。结论 血清总胆汁酸测定对于急性、慢性肝炎患者与血清丙氨酸氨基转移酶同样具有高度灵敏性。     

Acute and chronic toxicity studies with monochlorobenzene in rainbow trout

The toxicity of monochlorobenzene (CB) was investigated in rainbow trout following acute intraperitoneal (i.p.) administration and chronic exposure via the water in a continuously flowing system for 15 or 30 days.In the acute study overt toxicity and hepatotoxicity were monitored over a 96-h time period. Variables measured to assess toxicity included weight changes, liver weight to body weight ratios, behavioral changes, alanine aminotransferase activity (GPT), sulfobromophthalein (BSP) retention, total plasma protein concentration and liver histopathology. In the chronic study the same measures of toxicity were followed as well as food consumption and alkaline phosphatase (AP) activity.Upon acute i.p. exposure the toxicant (9.8 mmol/kg) caused behavioral changes in the fish which were consistent with the known anesthetic properties of CB in mammals. Elevations in BSP retention and GPT activity, and histopathology indicated that CB was hepatotoxic in fish.The LC₅₀ of CB in trout exposed via the water for 96 h was 4.7 mg/l. Chronic exposure of trout to 2 or 3 mg/l CB resulted in similar behavioral changes as seen in the acute study. Liver toxicity was evident from elevations in GPT activity. BSP retention and AP activity appeared to be affected by the nutritional status of the trout as much as by the CB treatment. After 30 days of exposure to 3 mg/l CB, trout appeared to have developed some tolerance to the toxic effects.     

A 13-week oral dose subchronic toxicity study of gardenia yellow containing geniposide in rats.

Gardenia yellow powders A, B and C, containing geniposide at 0.284%, 0.938% and 2.783%, respectively, were administered orally to male and female SD rats as 3% feed admixtures for 13-weeks to evaluate any potential toxicity. Mean geniposide intake values were 5.72, 18.9 and 56.3mg/kg/day in groups receiving these feed admixtures, respectively. All animals survived the duration of the study. The following findings were evident in the gardenia yellow C group: chromatouria, slightly increased plasma total bilirubin, blackish brown discoloration of the kidneys and liver, brown pigments in the proximal tubular epithelium of the kidneys. Slightly increased plasma total bilirubin was considered to be due to interference of metabolite of geniposide with the system of measurement and not to be a toxic effect since there were no related changes in histopathology of the liver or in any blood chemistry parameters. Other findings were limited to pigmentations or discolorations attributable to metabolites of geniposide. No treatment-related effects were evident on body weight, food consumption, ophthalmology, hematology or organ weights in any group. Therefore, it was concluded that 3-month ingestion of the gardenia yellow powder containing geniposide at 2.783% (approximately 60 mg/kg/day as geniposide intake) does not cause any severe toxic effects.     

人丙氨酸氨基转移酶基因(ALT1)的克隆、表达、纯化及酶活性的鉴定

目的克隆、表达、纯化重组人丙氨酸氨基转移酶(ALT1),并测定该酶活性,为建立特异性的ALT分型检测方法奠定基础。方法通过RT-PCR从肝癌细胞中扩增丙氨酸氨基转移酶(ALT1)基因,并将其克隆至pET-28 a表达载体中。重组表达质粒pET28 a-ALT1,转化大肠杆菌BL21,经1.0mmol.L-1IPTG诱导,表达可溶性重组融合蛋白,通过硫酸铵沉淀、镍离子柱亲和色谱及QHP柱色谱3步纯化,并检测融合蛋白活性。结果经过表达条件的优化增加了可溶性蛋白的表达,纯化后目的蛋白纯度达到85%,经测定重组蛋白具有很高的丙氨酸氨基转移酶活性(200 U.mg-1)。结论通过基因克隆及大肠杆菌表达,能得到活性较高的丙氨酸氨基转移酶蛋白。     

4epatic cytochrome P450s play a major role in monocrotaline-induced renal toxicity in mice

Aim：Monocrotaline （MCT） in plants of the genus Crotalaria induces significant toxicity in multiple organs including the liver, lung and kidney. Metabolic activation of MCT is required for MCT-induced toxicity. In this study, we attempted to determine whether the toxicity of MCT in kidney was a consequence of the metabolic activation of MCT in the liver. Methods： Liver-specific cytochrome P450 reductase-null （Null） mice, wild-type （WT） mice and CYP3A inhibitor ketoconazole-pretreated WT （KET-WT） mice were examined. The mice were injected with MCT （300, 400, or 500 mg/kg, ip）, and hepatotoxicity and nephrotoxic- ity were examined 24 h after MCT treatment. The levels of MCT and its metabolites in the blood, liver, lung, kidney and bile were deter- mined using LC-MS analysis. Results： Treatment of WT mice with MCT increased the serum levels of alanine aminotransferase, hyaluronic acid, urea nitrogen and creatinine in a dose-dependent manner. Histological examination revealed that MCT （500 mg/kg） caused severe liver injury and mod- erate kidney injury. In contrast, these pathological abnormalities were absent in Null and KET-WT mice. After injection of MCT （400 and 500 mg/kg）, the plasma, liver, kidney and lung of WT mice had significantly lower MCT levels and much higher N-oxide metabolites contents in compared with those of Null and KET-WT mice. Furthermore, WT mice had considerably higher levels of tissue-bound pyr roles and bile GSH-conjugated MCT metabolites compared with Null and KET-WT mice. Conclusion： Cytochrome P450s in mouse liver play a major role in the metabolic activation of MCT and thus contribute to MCT-induced renal toxicity.     

硒对硫唑嘌呤引起小鼠肝损伤的保护作用

小鼠灌胃给予Aza 10mg·kg~(-1)·d~(-1)及合用Selmg·kg~(-1)·d~(-1),连续用药1wk和2wk时观察血浆ALT,全血GSH,肝组织匀浆中MDA含量和GSH-Px活力变化.结果1wk和2wk时Aza组小鼠ALT、MDA均明显高于正常对照组,GSH、GSH-Px则明显低于对照组;加Se组则与之相反,ALT、MDA均降到正常,GSH、GSH-Px也明显升高,接近正常.光镜下见Aza组肝细胞明显变性坏死,加Se组则损害很轻微,接近正常.表明Se对Aza的肝损伤有保护作用.     

丙种球蛋白无反应型川崎病的预测指标

目的：寻找能预测川崎病患儿对丙种球蛋白（简称丙球,IVIG）治疗无反应的生物学指标.方法：回顾性分析310例IVIG治疗敏感及IVIG治疗无反应的川崎病患儿的病例资料.采用单因素方差分析,使用曲线下面积获得这些因素的临界值.对单因素分析结果提示与IVIG无反应有显著相关的因素,进行多元Logistic逐步回归分析.结果：在这310名患儿中,IVIG无反应型的有30例（占9.7％）,这部分患儿C反应蛋白、白细胞、中性粒细胞比值、谷草转氨酶、谷丙转氨酶、总胆红素和氨基末端脑钠肽前体高于对IVIG敏感的川崎病患儿.与川崎病对IVIG敏感的患儿相比,川崎病IVIG无反应型患儿血钠、高密度脂蛋白水平更低.结论：通过多元logistic回归分析证实,ALT≥84 IU/L,总胆红素≥15.39 μmmol/L是丙球无反应型川崎病的两个独立的预测因子.因此,ALT以及总胆红素水平升高可能是丙球无反应型川崎病患儿的有用的预测指标.