裙带菜中岩藻多糖提取工艺研究

目的：探讨热水浸提工艺参数对裙带菜中岩藻多糖含量的影响。方法：选择固液比（倍）、提取时间（min）、提取温度（℃）为考察因素，考察各工艺参数对裙带菜中岩藻多糖提取率的影响，根据其结果采用正交试验法确定提取裙带菜中岩藻多糖的最佳工艺。结果：100℃，60倍水量，提取7h，此为裙带菜中岩藻多糖的最佳提取工艺。经初步纯化后的裙带菜中岩藻多糖含量可达55．4％。结论：正交试验工艺研究的结果比较可靠。     

岩藻多糖的药理作用研究进展

岩藻多糖是从褐藻细胞壁和细胞间质中分离得到的一类天然硫酸化杂多糖。岩藻多糖具有多样的生物活性，如抗炎、抗肿瘤、神经保护、抗凝、调节肠道菌群、调节血脂、抗病毒作用。对岩藻多糖的药理作用进行了总结，以期为进一步开发利用岩藻多糖提供参考。     

岩藻聚糖硫酸酯降血糖作用机制的研究进展

糖尿病是以高血糖和胰岛素抵抗为特征的内分泌和代谢系统疾病,已成为世界范围内一种普遍疾病。岩藻多糖基于其特定的化学结构,如单糖组成和糖苷键,具有良好的降糖作用和理想的糖尿病治疗潜力。岩藻聚糖硫酸酯具有多种生物活性,但其结构复杂、高分子量和高粘性的特性限制了其应用,而低分子量岩藻多糖粘度低、溶解度好,且研究表明低分子量岩藻多糖具有更好的降血糖作用,因此其低分子量产物的研究具有重大意义。本文讨论了岩藻多糖的结构特征,包括主干结构、糖苷键位置、单糖类型、硫酸盐含量,着重介绍了多糖分子量和降血糖活性的关联,继而引申出低分子量降血糖作用及其作用机理,以期为明晰岩藻多糖的构效关系及进一步的应用提供理论基础。     

促肾上腺皮质激素释放因子I型受体：抗抑郁药物的新靶标

抑郁和焦虑患者常伴随应激激素调节失常,这与下丘脑神经肽促肾上腺皮质激素释放因子（CRF）和精氨酸加压素分泌过多密切相关。CRF主要通过激动促肾上腺皮质激素释放因子I型（CRF1）受体诱导抑郁或焦虑样症状,众多研究表明CRF1受体是新型抗抑郁药的潜在靶标。目前已研发出很多基于此靶标的非肽类小分子化合物,但只有一部分进入临床试验,包括NBI-30775／R121919和NBI-34041等。值得注意的是,此类化合物显效与动物的应激水平和自身焦虑程度有关,即CRF1受体拮抗剂可在不影响下丘脑-垂体-肾上腺轴基础活性情况下对抗CRF介导的病理性应激反应,从而提示其副作用可能较低。总之,小分子CRF1受体拮抗剂可能成为治疗应激相关精神疾病的新方法。本文重点综述CRF1受体作为新靶标在抑郁症治疗中的潜在应用。     

岩藻多糖体外抗KRV活性初步研究

目的 为了研究岩藻多糖体外抗Kilham rat virus（KRV）病毒的活性以及抑制炎症因子IL-1、IL-6的表达。方法 CCK-8法测得岩藻多糖对大鼠肾细胞（NRK）的半数细胞毒性浓度（CC50）;通过细胞病变效应测定药物的抗病毒活性,计算药物的半数抑制浓度（IC50）以及治疗指数（SI）;建立KRV感染大鼠肾细胞（NRK）细胞模型,设置阴性对照、病毒感染组以及治疗实验组,通过实时荧光定量PCR检测病毒以及IL-1、IL-6的表达水平。结果 CCK-8法测得药物的CC50 > 2500μg/mL,岩藻多糖的IC50为114.8±8.1μg/mL,治疗指数 > 21.78;qPCR结果表明KRV的转录水平实验组较阳性对照组明显降低,且IL-1、IL-6的转录水平亦显著降低。结论 岩藻多糖具有较小的细胞毒性以及良好的抗KRV病毒的效果,并且能够减轻病毒诱导的炎症反应,为防治病毒感染导致的糖尿病提供理论基础。     

铜藻岩藻多糖匀浆提取工艺及抗氧化活性分析

目的 优化铜藻岩藻多糖的匀浆提取工艺,并测定其抗氧化活性。方法 以岩藻多糖的提取率为指标,基于单因素试验的基础上,采用响应面法对铜藻中岩藻多糖的提取工艺进行优化,并对其抗氧化活性进行验证。结果 最佳提取工艺条件为提取时间6 min、提取温度94℃、液料比34 mL·g^-1和提取次数2次。在此条件下,多糖的提取率为14.76%。抗氧化活性研究结果表明,铜藻岩藻多糖在质量浓度为0.2～10.0 mg·mL^-1范围内有一定的抗氧化活性,对DPPH自由基、ABTS⁺自由基清除率的IC₅₀分别为0.22、0.41 mg·mL^-1。结论 该提取工艺高效,可为铜藻岩藻多糖的制备及应用提供理论依据。     

岩藻多糖的生物活性研究

岩藻多糖是一种由岩藻糖基和岩藻糖-4-硫酸酯基组成的高分子多糖，来源于二色桌片参。采用体外细胞培养技术，研究了岩藻多糖体外对HIV-I感染MT4细胞的影响及其细胞毒性作用。结果表明：岩藻多糖可明显抑制HIV-I对MT4细胞的急性感染，其半数有效浓度(EC50)为8.934μgmL^-1；岩藻多糖体外对MT4细胞的半数中毒浓度为1245mg.mL^-1，治疗指数达139215。这提示岩藻多糖为一种低毒性的HIV-I增殖的抑制剂。     

岩藻多糖对刀豆蛋白A诱导的肝脏损伤抑制作用的研究

<正>岩藻多糖明显减轻刀豆蛋白A(Con A)诱导的肝细胞损害,可能是通过抑制P选择素介导的血小板与白细胞作用,从而减少炎性细胞的浸润。P选择素是一类表达于血小板alpha微粒及内皮细胞Weibel-Palade小体的糖蛋白[1]。研究表明P选择素是介导白细胞与血小板及内皮细胞作用的重要分子,并且在炎症过程中起重要作用[1]。岩藻多糖是一种由岩藻糖基和岩藻糖-4-硫酸酯基组成的高分子多糖,具有抗炎、抗病毒、抗肿瘤等广泛作用[2]。近年来发现岩藻多糖抑制炎症     

网格状与线状鼠尾藻多糖抗炎作用研究

目的 对鼠尾藻多糖进行分离纯化，并对其理化特性、微观结构和对炎症因子表达的影响进行研究。方法 采用热水提取法及DEAE-Sepharose CL-6B和Sephacryl S-300 HR柱层析分离纯化鼠尾藻多糖，利用高效空间排阻色谱法（HPSEC）、气相色谱法（GC）、红外光谱法（FTIR）和透射电子显微镜（TEM）研究理化特性及微观结构，实时荧光定量PCR法研究炎症相关因子的mRMA表达。结果 得到两种鼠尾藻均一多糖STP-I和STP-III，相对分子质量分别是29 和350 kDa，糖含量均超过96%。透射电子显微镜观察到STP-I是网格状结构，STP-III是线状且螺旋缠绕结构。活性研究表明，STP-III能更好地抑制脂多糖（LPS）诱导下小鼠巨噬细胞RAW264.7系炎症因子TNF-α、IL-6和COX-2的mRNA表达量，在150 μg?mL1质量浓度下，STP-III对炎症因子TNF-α、IL-6和COX-2的mRNA表达抑制率均超过95%。结论 鼠尾藻多糖具有抗炎症因子表达的作用，可以作为潜在的抗炎药物开发。线状缠绕的鼠尾藻多糖STP-III较网格状的STP-I能更好地抑制炎症相关因子的表达。     

大黄甘草汤为主治疗慢性肾功能衰竭疗效观察

进行性肾功能减退是几乎所有慢性肾脏病持续不愈的最终结局，如何延缓慢性肾功能不全的进展已成为国内外瞩目的重要课题。国内外报告应用小剂量多巴胺与速尿对肾功能有改善作用[1，2]。以大黄为主治疗慢性肾功能衰竭（CRF）患者已有许多经验介绍[3，4]，我们把两者结合起来，以大黄甘草汤为主治疗CRF，以观察其疗效，为中西结合治疗CRF提供参考。     

Effects of fucoidan on chronic renal failure in rats

The effects of fucoidan on chronic renal failure (CRF) were investigated in vivo in a subtotal nephrectomy CRF model and a cryoinjury induced CRF model in rats. Fucoidan showed renoprotective effects in both models. Fucoidan (100 or 200 mg/kg, orally) significantly decreased elevated serum creatinine and urea nitrogen levels. Histopathological changes of renal tubules and interstitium were markedly alleviated by fucoidan and the mesangial areas were also greatly reduced. The activities of fucoidan were dose-dependent.     

Emerging drugs for renal failure

Renal failure involves a significant impairment of the essential functions of the kidney, which can be either acute with sudden and rapid onset (acute renal failure [ARF]) or chronic with gradual onset (chronic renal failure [CRF]). ARF, if detected early, may be halted or reversed, whereas CRF is generally irreversible. Without treatment or intervention, both forms of renal failure lead to end stage renal failure (ESRF) or end stage renal disease (ESRD), requiring renal replacement therapy (RRT) in the form of dialysis or renal transplantation for survival. However, provision of RRT requires expert teams working in specialised units, making therapy of patients with renal failure expensive; furthermore, RRT is complex, with its own complications. Although pharmacological interventions have shown promise in experimental models, these have not been as successful in the clinical setting (e.g., administration of atrial natriuretic peptide, low-dose dopamine). At present, drugs are administered during CRF to either reduce one of the many risk factors of CRF (e.g., angiotensin-converting enzyme inhibitors, statins) or to deal with the consequences of CRF (e.g., erythropoietin, calcitriol). Recent evidence suggests that some of these interventions may provide further direct beneficial effects via reduction of renal inflammation. Although these interventions have greatly improved the prospects for patients suffering ESRF, the development of novel drugs and therapies with which to reduce the consequences of renal failure and ESRD remain topics of great interest. This article reviews the therapies available for the prevention and management of renal failure in adults and describes, in detail, emerging drugs and novel interventions that may soon become available for the treatment or prevention of ESRF.     

治疗慢性肾衰的海洋新药FPS的研究

海洋新药裸藻多糖硫酸酯（ＦＰＳ）是从褐藻中提取的特效组分，具有抗凝血、降血脂、抗肿瘤和抗ＨＩＶ的作用。多年来通过对ＦＰＳ药学、药理和毒理进行的系统研究以及前期临床四年来对５００余例病人的观察，发现它对治疗心脑血管疾病和中、早期慢性肾衰效果好、无毒副作用，特别对改善肾功能、提高肾脏对肌酐清除率效果尤为显著。ＦＰＳ在国内外首先用于治疗慢性肾衰，是有前途和值得开发的天然海洋新药。     

三黄肾康丸治疗大鼠慢性肾衰的实验研究

目的 :观察三黄肾康丸对腺嘌呤致大鼠慢性肾衰 (CRF)的影响。方法 :连续喂养0 75 %腺嘌呤使Wister大鼠产生类似于人慢性肾衰的症状。2周后 ,治疗组大鼠每天用中药三黄肾康丸 (12 0g/kg、6.0g/kg)灌胃 ,连续6周 ,并于第4、8周测定大鼠血尿素氮 (BUN )、肌酐 (Scr)、RBC、HGB、HCT及肾脏病理学检查。结果 :三黄肾康丸明显改善大鼠肾衰的症状 ,与模型组大鼠比较 ,肾重量减轻 (P<0 01) ,纤维化程度降低 ,肾组织内结晶沉积物减少。结论 :三黄肾康丸对大鼠肾衰有明显治疗效果     

The effect of chronic renal failure on drug metabolism and transport

BACKGROUND: Chronic renal failure (CRF) has been shown to significantly reduce the nonrenal clearance and alter bioavailability of drugs predominantly metabolized by the liver and intestine. OBJECTIVES: The purpose of this article is to review all significant animal and clinical studies dealing with the effect of CRF on drug metabolism and transport. METHODS: A search of the National Library of Medicine PubMed was done with terms such as chronic renal failure, cytochrome P450 [CYP], liver metabolism, efflux drug transport and uptake transport, including relevant articles back to 1969. RESULTS: Animal studies in CRF have shown a significant downregulation (40-85%) of hepatic and intestinal CYP metabolism. High levels of parathyroid hormone, cytokines and uremic toxins have been shown to reduce CYP activity. Phase II reactions and drug transporters such as P-glycoprotein and organic anion transporting polypeptide are also affected. CONCLUSION: CRF alters intestinal, renal and hepatic drug metabolism and transport producing a clinically significant impact on drug disposition and increasing the risk for adverse drug reactions.     

Protective role of gamma-aminobutyric acid against chronic renal failure in rats

The protective effect of gamma-aminobutyric acid (GABA) against chronic renal failure (CRF) was investigated using a remnant kidney model with 5/6 nephrectomized rats. Nephrectomy led to renal dysfunction, which was evaluated via several parameters including serum urea nitrogen, creatinine (Cr) and Cr clearance. However, the administration of GABA ameliorated renal dysfunction, and a longer administration period of GABA increased its protective effect. In addition, nephrectomized control rats showed an elevation in the fractional excretion of sodium (FE(Na)) with an increase in urinary sodium, while GABA led to a significant decline in FE(Na). Moreover, nephrectomy resulted in a decrease of serum albumin and an increase of urinary protein with a change in the urinary protein pattern, whereas the rats administered GABA showed improvement in these changes associated with CRF caused by nephrectomy. This suggests that GABA would inhibit the disease progression and have a protective role against CRF. As one of the risk factors for CRF progression, hypertension was also regulated by GABA. The results also indicate that GABA may play a protective role against CRF through improvement of the serum lipid profile, with reductions in triglyceride and total cholesterol. Furthermore, nephrectomy led to renal oxidative stress with a decrease in the activity of antioxidative enzymes and elevation of lipid peroxidation. The administration of GABA attenuated oxidative stress induced by nephrectomy through an increase in superoxide dismutase and catalase, and decrease in lipid peroxidation. The histopathological lesions, including glomerular, tubular and interstitial lesions, under nephrectomy were also improved by GABA with the inhibition of fibronectin expression. This study demonstrated that GABA attenuated renal dysfunction via regulation of blood pressure and lipid profile, and it also ameliorated the oxidative stress induced by nephrectomy, suggesting the promising potential of GABA in protecting against renal failure progression.     

促红细胞生成素治疗肾性贫血的疗效观察

目的:观察促红细胞生成素治疗肾性贫血的疗效及不良反应。方法:128例肾性贫血患者皮下注射促红细胞生成素,疗程12wk,采用自身对照法观察临床治疗后情况。结果:显效91例,有效33例,总有效率为96.88%;不良反应有血压升高、透析器内凝血、注射部位疼痛、头痛,未发现严重不良反应;非透析治疗患者用药期间未见明显肾功能恶化。结论:促红细胞生成素治疗肾性贫血安全、有效。     

慢性肾功能衰竭对P-糖蛋白及其介导的药物转运的影响

综述慢性肾功能衰竭(chronic renal failure,CRF)对P-糖蛋白(P-glycoproteins,P-gp)及其介导的药物转运的影响。通过查阅资料,选取有代表性的文献,分别从动物水平、细胞水平、临床研究三个方面进行综述。CRF会使药物的肾脏和非肾脏清除发生改变,但不同组织细胞中P-gp的表达与活性改变是不同的,总体而言,CRF会抑制肠道、肾脏和血脑屏障中P-gp的外排作用而促进肝脏中P-gp的药物外排作用。了解CRF对P-gp的影响,充分认识CRF对药物体内过程的影响,将有助于提高CRF患者用药的安全性。     

丹参多酚酸盐对大鼠慢性肾衰时肾功能及内源性内皮素释放的影响

采用腺嘌呤致大鼠慢性肾衰 (CRF)的模型 ,研究丹参多酚酸盐对CRF大鼠肾功能及内源性内皮素释放的影响 .结果表明 ,在CRF模型中 ,大鼠血清尿素氮 ,肌肝水平 ,血浆内皮素水平及肾皮质钙含量均明显升高 ;丹参多酚酸盐 5,10 ,15mg·kg- 1,ip连续给药 14d ,则使CRF大鼠的血清尿素氮 ,肌肝水平降低 ,丹参多酚酸盐 10mg·kg- 1组的血清尿素氮已与正常对照组无显著差异 (P >0 .0 5) .另外 ,与CRF大鼠相比 ,丹参多酚酸盐 5,10 ,15mg·kg- 1组血浆内皮素水平及肾皮质钙含量均明显降低 ,10mg·kg- 1组与 15mg·kg- 1组无显著差异 ,10mg·kg- 1组内皮素水平及肾皮质钙含量较模型组分别降低了59 % ,51% .形态及定量检测肾小管平均截面积 ,肾小球平均体积的结果表明 ,丹参多酚酸盐 10mg·kg- 1组能减少肾组织结晶沉淀物 ,减轻肾小管 ,肾小球损伤程度 ,延缓肾小球基底膜增厚 .结果提示 ,丹参多酚酸盐能明显改善肾功能 ,其机理可能与其抑制内皮素的释放有关     

阿托伐他汀对慢性肾衰竭大鼠外周血内皮祖细胞的影响

目的探讨阿托伐他汀对慢性肾衰竭大鼠外周血内皮祖细胞(endothelial progenitor cells,EPCs)数量和功能的影响。方法采用分阶段5/6肾切除制备大鼠慢性肾衰竭模型。实验动物随机分为4组:假手术组、慢性肾衰竭组(模型组)、8mg.kg-1.d-1阿托伐他汀干预组(小剂量组)、16mg.kg-1.d-1阿托伐他汀干预组(大剂量组)。大鼠阿托伐他汀灌胃8周后,取其外周血分离与培养EPCs,并检测EPCs数量及其增殖、黏附能力。结果与假手术组比较,慢性肾衰竭大鼠外周血EPCs数量及其增殖、黏附能力均下降(P<0.05)。应用阿托伐他汀能明显增加慢性肾衰竭大鼠外周血EPCs数量,改善外周血EPCs增殖、黏附能力(P<0.05),并且呈剂量依赖性。结论阿托伐他汀可改善慢性肾衰竭大鼠外周血EPCs的数量和功能。