皂苷类成分吸收分布和代谢及排泄研究进展

皂苷是一类具有多种药理活性的重要天然产物,但由于其生物利用度普遍较低,体内的药效物质基础和作用机制研究尚不够深入,影响了该类成分的新药开发与应用。本文对近年来国内外关于皂苷类化合物体内外代谢等过程研究的文献进行综述,有利于深入探索该类成分的体内药效物质基础和作用机制,为新药研发提供一定的理论依据。     

Concurrent repletion of iron and zinc reduces intestinal oxidative damage in iron- and zinc-deficient rats

AIM： To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance. METHODS： Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet （〈 6.5 mg Fe and 4.0 mg Zn/kg diet） for 4 wk were randomly divided into three groups （n = 8, each） and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron ＋ 3.3 mg zinc for 2 wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of SSFe or ^65Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein. Duodenal homogenates （mitochondrial and cytosolic fractions）, were used to assess aconitase activity, oxidative stress, functional integrity and the response of antioxidant enzymes. RESULTS： Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were teated with iron or zinc alone; these data provide evidence for antagonistic interactions. This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression, but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage.CONCLUSION： Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron supplementation.     

盐酸氯米帕明大鼠在体肠吸收动力学研究

目的研究盐酸氯米帕明在大鼠肠道的吸收特性。方法采用大鼠在体肠灌流实验方法,利用高效液相色谱法同时测定肠回流液中药物及酚红的浓度,通过酚红的浓度校正相应时刻供试液的体积。结果盐酸氯米帕明浓度为5、10、25μg/ml时小肠的吸收速率常数(ka)为(0.74±0.04)、(0.78±0.03)、(0.77±0.05)h-1;在十二指肠、空肠、回肠和结肠的ka分别为(0.590±0.026)、(0.670±0.032)、(0.680±0.030)和(0.560±0.031)h-1。结论盐酸氯米帕明在大鼠肠道均有良好的吸收。盐酸氯米帕明在小肠的吸收呈表观一级动力学过程,吸收机制为被动扩散。     

Evaluation of intestinal absorption enhancement and local mucosal toxicity of two promoters. I. Studies in isolated rat and human colonic mucosae

The effects of two absorption promoters, (sodium caprate (C₁₀) and melittin), on intestinal permeability and viability were measured in intact rat and human colonic epithelia mounted in Ussing chambers. Apical-side addition of C₁₀ (10 mM) and melittin (10–50 μM) rapidly reduced the transepithelial electrical resistance (TEER) and increased the apparent permeability coefficient (Papp) of [¹⁴C]-mannitol and FITC-dextran-4 kDa (FD4) across colonic mucosae from both species. Effects of C₁₀ on flux were greater than those of melittin at the concentrations selected. C₁₀ irreversibly decreased TEER, but the effects of melittin were partially reversible. Enhanced permeability of polar sugars (0.18–70 kDa) in colonic mucosae with C₁₀ was accompanied by significant release of lactate dehydrogenase (LDH) from the luminal surface as well as by inhibition of electrogenic chloride secretion induced by the muscarinic agonist, carbachol (0.1–10 μM). Although melittin did not alter electrogenic chloride secretion in rat or human colonic mucosae, it caused leakage of LDH from rat tissue. Gross histology and electron microscopy of rat and human colonic mucosae demonstrated that each permeation enhancer can induce colonic epithelial damage at concentrations required to increase marker fluxes. C₁₀ led to more significant mucosal damage than melittin, characterised by sloughing and mucosal erosion. Overall, these results indicate that while C₁₀ and melittin increase transport of paracellular flux markers across isolated human and rat colonic mucosae in vitro, these effects are associated with some cytotoxicity.     

芒果苷大鼠在体肠道吸收机制研究

目的:研究芒果苷大鼠在体肠道吸收机制。方法:采用大鼠在体肠段灌流模型,建立高效液相色谱/紫外分光光度法测定肠循环液中芒果苷的浓度,研究不同芒果苷浓度、胆汁及吸收部位对芒果苷吸收参数的影响。结果:芒果苷在5.0~25.0μg.mL-1浓度范围内对小肠吸收速率常数(Ka)无影响;在12.5μg.mL-1浓度下对结扎胆管大鼠的小肠Ka有影响;各肠段的Ka回肠>空肠>结肠>十二指肠,分别为0.164、0.132、0.125、0.107h-1。结论:芒果苷的吸收符合一级动力学特征,吸收机制为被动扩散;芒果苷在各肠段均有较好的吸收,胆汁使芒果苷在小肠的透过系数增大。     

不同提取方法菟丝子中总黄酮和微量元素铜含量的相关性分析

目的：通过对不同提取方法菟丝子样品中总黄酮和微量元素铜含量的测定,分析总黄酮与微量元素铜含量之间的相关性。方法：分别采用常规回流法、微波辅助萃取法和石油醚脱脂-索氏提取法对中药菟丝子进行提取,以芦丁为对照品,用紫外分光光度法测定提取液中总黄酮的含量,用原子吸收分光光度法测定提取液中微量元素铜的含量。以总黄酮和微量元素铜的含量为考察指标,探讨中药菟丝子中总黄酮与微量元素铜之间的相关性。结果：微波辅助萃取的样品中总黄酮和微量元素铜的含量均高于其他提取方法,石油醚脱脂-索氏提取的样品中总黄酮和微量元素铜的含量均低于其他提取方法。结论：中药菟丝子中总黄酮的含量与微量元素铜的含量呈正相关关系。     

不同粒径超细碳酸钙在小鼠体内的吸收率

目的:探讨不同粒径超细碳酸钙在小鼠体内吸收率。方法:选用3周断乳小鼠40只,喂食2周基础饲料后,按体重平均分为对照组和3个实验组。对照组继续喂食基础饲料,3个实验组分别喂食不同粒径超细碳酸钙+基础饲料。连续喂养4周,做3 d钙代谢实验。结果:各实验组小鼠体重、身长、钙吸收率均明显高于对照组(P<0.01),结论:超细碳酸钙粒径越小,吸收效果越好。     

全血中铅的石墨炉原子吸收光谱测定法

目的探讨石墨炉原子吸收光谱测定全血中铅的方法。方法用氯化钯作为基体改进剂,全血用4％硝酸脱去蛋白,经离心后后取上清液直接进样,氘灯校正背景,石墨炉原子吸收法进行测定。结果方法的线性范围为0～80μg／L,相关系数为0．9998,RSD为1．9％-6．05％,加标回收率为96．0％～101％,方法的检出限为0．5μg/L。结论该法准确度、精密度良好,样品不需消化,污染小,是一种简单、快速、可行的测定全血铅的方法。