Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

斑蝥素脂质体凝胶剂的研制与质量评价

目的 :研究斑蝥素脂质体凝胶的制备工艺 ,并初步评价其质量。方法 :用均匀设计法优选斑蝥素脂质体 (LC)的最佳处方及制备工艺 ,借助数字显微镜及病理图像分析系统 (MoticB5 professionalseries)观测其外观、大小及分布 ;用离心法结合GC法测定其包封率及渗漏率 ;并进一步将其制成凝胶剂 ,初步观察其稳定性 ,并以家兔为试验对象与对照品 (较膏剂 )比较其皮肤刺激性 ,用大鼠离体皮肤的扩散实验与对照品比较斑蝥素的透皮扩散情况。结果 :所得脂质体外观圆整 ,粒径分布均匀 ,平均包封率为 (79.7± 1 .2 ) %(n =5 ) ,稳定性良好 ;所得凝胶剂为半透明粘稠状胶体 ,与对照品相比皮肤刺激性显著减小 ,2 4h后皮肤内斑蝥素的滞留量显著增加 (为对照组的 2 .6倍 ) ,而透皮扩散的量极微。结论 :该脂质体凝胶制备工艺可行 ,质量稳定 ,检测方法可靠 ,高效、低毒 ,可望成为临床治疗斑秃的新制剂。     

复方斑蝥胶囊对原发性肝癌患者免疫功能及临床疗效的影响

目的探讨复方斑蝥胶囊对原发性肝癌患者临床疗效及免疫功能的影响。方法选取2017年3月—2019年3月住院治疗的中晚期原发性肝癌患者共100例,按随机数字表法分为对照组与治疗组,每组各50例。对照组给予肝动脉插管栓塞化疗(Transcatheter arterial chemoembolization,TACE)治疗,治疗组在对照组治疗基础上给予复方斑蝥胶囊治疗。观察两组患者治疗前后临床效果、肿瘤标志物甲胎蛋白(A-fetoprotein,AFP)、癌胚抗原(Carcino-embryonic antigen,CEA)、糖抗原199(carbohydrate antigen 199,CA199)含量,免疫细胞因子血管内皮生长因子(vascular endothelial growth factor,VEGF)和缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)水平及生活质量变化。结果治疗后,对照组总有效率为76%;治疗组总有效率为84%。治疗组总有效率明显高于对照组,差异有统计学意义(P<0.05)。治疗后对照组患者AFP、CA199含量降低,与治疗前比较,差异有统计学意义(P<0.05),CEA值虽有降低,但差异无统计学意义(P>0.05);治疗后治疗组患者血清中AFP、CEA、CA199含量显著降低,与治疗前比较,差异有统计学意义(P<0.05);且治疗组患者治疗后AFP、CEA、CA199含量降低程度优于对照组,差异有统计学意义(P<0.05)。两组患者治疗后血清中VEGF、HIF-1α含量均明显降低,与治疗前比较,差异有统计学意义(P<0.05);且治疗组患者血清中VEGF、HIF-1α含量降低优于对照组,差异有统计学意义(P<0.05)。治疗后治疗组KPS评分升高患者24例(48%),ZPS评分升高患者25例(50%),与对照组比较差异有统计学意义(P<0.05)。结论复方斑蝥胶囊联合TACE能显著提高原发性肝癌患者的临床效果,抑制肿瘤细胞的增殖,提高生存率,改善生活质量。     

去甲斑蝥素致大鼠腹腔炎症与多脏器功能失常综合征

目的：探讨去甲斑蝥素致大鼠失控炎症在多脏器功能失常综合征（ＭＯＤＳ）发病中的作用。方法：将去甲斑蝥素（一种能刺激皮肤发泡以收集巨噬细胞的致炎物质，１５ｍｇ／ｋｇ）注入６０只Ｗｉｓｔａｒ大白鼠腹腔，动态观察其对炎性介质以及器官形态和功能的影响。结果：与对照组比较，实验组动脉血氧分压（ＰａＯ２）和血小板计数明显下降，谷丙转氨酶（ＧＰＴ）和血肌酐（ＳＣｒ）明显升高，１２０小时后上述指标均接近对照组；１２小时和２４小时大鼠死亡率分别为１５％和２０％；肿瘤坏死因子（ＴＮＦ）和磷脂酶Ａ２（ＰＬＡ２）在注射后２４小时和１２小时达最高值；肺、心、肝、肾、肠等器官出现病理改变。结论：去甲斑蝥素可能通过激活巨噬细胞、释放ＴＮＦ等炎性介质诱发全身炎症和ＭＯＤＳ。     

毛细管气相色谱法测定抗鼻咽癌口服液中斑蝥素的含量

目的:建立了抗鼻咽癌口服液中斑蝥素的含量测定方法。方法:选用DB-5弹性石英毛细管柱(30 m×0.25 mm,0.25μm);检测器为FID检测器;柱温为150℃,保持25 min;气化室温度为250℃;检测器温度为320℃;载气为氦气;柱头压力为140 kPa;分流比为30∶1。结果:斑蝥素在0.02~0.24μg范围内呈良好的线性关系,r=0.999 8(n=6);样品的平均加样回收率为97.24%,RSD=1.35%(n=6)。结论:本法简便、快速,可用于抗鼻咽癌口服液的质量控制。     

加温合并喜树碱、斑蝥素对荷Lewis肺癌小鼠的作用

本文探讨了加温合并喜树碱、斑蝥素对荷Ｌｅｗｉｓ肺癌ＮＩＨ小鼠的抗肿瘤作用以及热耐受性对其作用的影响。结果：①喜树碱１６ｍｇ／ｋｇ或斑蝥素０．４５ｍｇ／ｋｇ合并２５ｍｉｎ加温能抑制肿瘤生长，在４１～４３℃范围内随温度的升高而加强；②在加温４３℃，２５ｍｉｎ时，加温合并喜树碱１２ｍｇ／ｋｇ或斑蝥素０．４５ｍｇ／ｋｇ产生相加作用；③热耐受性在４３℃，２５ｍｉｎ加温后迅速产生，２４ｈ达高峰而后递减；热耐受性极大地影响了喜树碱和斑蝥素的抗癌效果。     

斑蝥、青娘子、红娘子鉴别研究(英文)

目的:研究建立斑蝥(Mylabris)、青娘子(Lytta)、红娘子(Huechys)3个毒性药材的鉴别分析方法。该3个药材具有特殊的药理活性如抗体活性、抗子宫颈癌等。方法:除形态外观和显微鉴别外,本文研究建立气相色谱和毛细管电泳鉴别特征成分指纹图谱的方法。气相色谱分析主要测定药材中斑蝥素成份而毛细管电泳指纹图谱则集中药材的氨基酸分布。结果:所建立的方法可为验证该3个药材的质量提供参考。结论:研究发现青娘子与斑蝥一样含有斑蝥素但含量很低,而红娘子不含斑蝥素。     

羟苯磺酸钙对去甲斑蝥素致血管内皮细胞毒性拮抗作用的研究

目的 探讨羟苯磺酸钙对去甲斑蝥素致血管内皮细胞损伤的影响,并测定羟苯磺酸钙的有效拮抗作用浓度.方法 将体外培养人脐静脉内皮细胞系完全随机分为对照组、毒性组和干预组.对照组用DMEM培养基培养48 h;毒性组用含去甲斑蝥素浓度为50μmol/L的DEME培养基培养48 h;干预组分为7组,分别加入含羟苯磺酸钙5、10、20、60、80、100和200 mmoL/L的DMEM培养基中再培养46h.测定细胞存活率.结果 干预组细胞存活率随着羟苯磺酸钙剂量的增加而升高,羟苯磺酸钙剂量达80 mmol/L时,细胞存活率明显升高.四甲基偶氮唑盐微量酶反应比色法测定的干预组(5 mmol/L)细胞存活率与毒性组相近,差异无统计学意义(P＞0.05),干预组(200 mmol/L)细胞存活率高于毒性组,组间比较差异有统计学意义[(69.4±3.8)％比(49.5±1.0)％,P＜0.05].结论 去甲斑瞀素抑制内皮细胞增殖,降低细胞存活率,当羟苯磺酸钙的浓度为80 mmol/L时,对去甲斑蝥素的毒性具有明显拮抗作用,能有效保护血管内皮细胞.     

斑蝥素贴剂结合维生素C静脉注射辅助治疗带状疱疹1例（英文）

The diagnosis and therapy for herpes zoster(HZ)are frequently associated with consultation of a general practitioner and with hospital care.Although there are several serious complications of zoster such as ophthalmic,splanchnic,cerebral,and motor conditions,the most common and feared in immunocompetent adults is postherpetic neuralgia(PHN).Its definition is controversial.Recent data support the distinction between acute herpetic neuralgia(within 30 d of rash onset),subacute herpetic neuralgia(30 to 120 d after rash onset),and postherpetic neuralgia(defined as pain lasting at least 120 d from rash onset)[1-3].PHN is classified as a neuropathic pain that is associated with mechanical allodynia where normally innocuous tactile stimuli are perceived as painful[2].In actual studies it is reported that the incidence of HZ is 3.2 to 4.1 in 1 000 person-years[4,5].     

斑蝥及其近缘种属药用资源研究进展

作者综述了近年来斑蝥及其近缘种属药用资源的研究进展.以有代表性的论文为依据,进行分析、整理和归纳.含斑蝥素昆虫,除芫菁科7属45种外,还有同翅目蜡蝉科的鼻蜡蝉属Zanna、蜡蝉属Fulgora、翅蜡蝉属Lycorma,鞘翅目拟天牛科中Oxocopis属、Heliocis属、沃黄拟天牛属Xanthochroa,曹氏拟天牛属Oedemera等7个近缘属9种.斑蝥素药用新资源丰富,斑蝥素生物合成具有生物亲缘关系,斑蝥素形成与生态有一定关系,活体提取等斑蝥资源利用的新方法受到重视.