白内障动物模型的建立及评价参数的研究进展

目的综述多种白内障动物模型的建立方法与评价参数,以便更好地研究白内障的发病机制、晶状体自身修复过程以及考察药物的治疗效果。方法结合中外研究文献,按照硒性、糖性、萘性、氧化损伤型、外伤性、钝挫伤以及遗传性白内障分类,依次介绍模型的建立方法和常用评价指标。结果所用造模试剂均能有效造模,造模成功后晶状体混浊度、生化指标等均发生显著变化。结论白内障模型建立方法很多且可以通过一系列评价参数进行评价。     

白内障动物模型及药物治疗研究进展

白内障的防治一直是防盲治盲工作的重点,但其发病机制尚不完全清楚,目前临床上还缺少有效的治疗药物。构建及选择合适的白内障动物模型不仅是深入研究白内障发病机制的重要基础,也是临床筛选和评价防治白内障药物的有效手段。因此就近年来国内外有关人工诱导性和先天性白内障动物模型的构建方式、特点及在药物评价研究发面的应用进行综述,并总结基于不同药理机制的抗白内障药物研究进展,提出目前应增加晶状体聚集蛋白溶解药物的发现,以期推动白内障药物治疗的发展。     

白内障药物治疗进展

老年性白内障是我国的主要致盲眼病之一,它的早期诊断相对较容易,若在白内障的发病初期就能使用经济有效的药物治疗,那么就会推迟手术的时间,甚至可以维持终生不受手术的困扰。抗白内障的各种药物对该病的治疗疗效是肯定的,由于白内障的病因及发病机制比较复杂;各种学说分别从不同的侧面来诠释了它的发病机制。     

糖尿病性白内障研究进展

糖尿病性白内障是一类重要的代谢型白内障,大量实验研究表明有3种学说是该病可能的发病机制,即渗透压学说、蛋白质糖基化学说和氧化应用学说。长期以来,渗透压学说被广泛支持和认可,但随着研究的深入,蛋白质糖基化学说开始占有越来越重要的地位。研究糖尿病性白内障的发病机制和治疗,具有非常重要的价值。     

药物性白内障及其发病机制的研究进展

白内障在全球致盲性疾病中始终占居首位,给全球带来了巨大负担。白内障的发生与诸多因素有关,如年龄、辐射、糖尿病等。临床上有些药物的使用也是其危险因素之一,如糖皮质激素、吩噻嗪类药物、他汀类药物等。该文回顾了近年来一些药物性白内障的最新研究成果,在此基础上进行归纳总结,阐述了与白内障相关的多种药物和其相关性白内障的发病机制,以期望可以对临床医师和不同类型白内障发病机制的相关研究有所帮助。     

白内障与过氧化反应

白内障与过氧化反应杜冠华，张均田（中国医学科学院药物研究所，北京１０００５０）白内障是眼科常见疾病，引起白内障的原因很多，如老年性白内障，糖尿病性白内障，光线损伤造成的白内障等等。白内障的发病机制也各有不同，多年的研究证明，眼内氧化作用增强（ｏｘｉｄ...     

支气管哮喘药物治疗评价

支气管哮喘是一种发病机制复杂的气道慢性炎症,临床有众多作用机制不同的药物可选用,但目前药物治疗尚无法彻底予以根治.正确认识并合理选择和使用药物可有效缓解哮喘患者症状,减少急性发作频数,改善预后.本文综述哮喘治疗药物相关研究近况.     

白内障术后干眼的机制研究进展

干眼是一种眼表疾病,也是白内障患者术后最常见的不适主诉。多种因素均会导致干眼的发生,随着国内外研究的不断进展,对于干眼的认识逐渐深入。现就白内障手术切口、泪膜分泌腺体、手术时长、药物、心理等方面对白内障围手术期与干眼发病相关的因素进行综述,以帮助眼科医师更好地开展临床诊疗工作。     

白内障术后干眼机制研究进展

摘要：干眼是一种眼表疾病,也是白内障患者术后最常见的不适主诉。多种因素均会导致干眼的发生,随着国内外研究的不断进展,对于干眼的认识逐渐深入。现就白内障手术切口、泪膜分泌腺体、手术时长、药物、心理等方面对白内障围手术期与干眼发病相关的因素进行综述,以帮助眼科医师更好地开展临床诊疗工作。     

白内障的处方，没有药物

多年来,人们对白内障的病因和发生机制进行了大量研究,针对不同的病因,应用不同的药物治疗白内障。目前,尽管世界范围内有近四十多种抗白内障的药物在临床上广泛应用,但其疗效均不十分确切。     

细胞色素C滴眼剂的制备及药效学

目的制备细胞色素C滴眼剂,并对其基本性质与对硒致白内障大鼠的抗白内障作用进行初步研究。方法对制得的滴眼剂进行pH与澄明度、黏度与渗透压及酶活力与药效学考察。结果与结论制剂各项指标符合2000年版《中华人民共和国药典》对滴眼剂的要求,且具有良好的抗白内障活性。     

硫普罗宁眼用凝胶的生物利用度及抗白内障作用

目的考察硫普罗宁眼用原位凝胶生物利用度及抗白内障效果。方法采用连续取样技术,通过柱前衍生化方法考察药物在兔眼房水中的动力学行为。利用硒性白内障大鼠晶状体混浊度的裂隙灯图像分析,动态考察硫普罗宁眼用原位凝胶的抗白内障作用。结果高剂量组硫普罗宁原位凝胶药物-时间曲线下面积为水溶液组的1.58倍。硫普罗宁原位凝胶和水溶液均延缓白内障的发生时间,前者作用尤佳,晶状体混浊度仅达到12%。结论与水溶液相比,硫普罗宁原位凝胶可提高眼内生物利用度,明显延缓白内障形成。     

Pharmacokinetic and pharmacodynamic evaluation of the anti-cataract effect of eye drops containing disulfiram and low-substituted methylcellulose using ICR/f rats as a hereditary cataract model

We attempted to develop anti-cataract eye drops using disulfiram (DSF) and low-substituted methylcellulose (MC), and evaluated their anti-cataract effect in terms of the lens opacification vs. age-profile curves using a one-exponential equation. The eye drops were prepared using 0.5% DSF and 2% MC (DSF eye drops), and ICR/f rats, a recessive-type hereditary cataractous strain, were used as the experimental model. Gelation of DSF eye drops containing MC was first observed at about 35°C, close to body temperature. In in vivo transcorneal penetration experiments using rabbit corneas, only diethyldithiocarbamate (DDC) was detected in the aqueous humor, while DSF was not detected. The DDC penetration level of DSF eye drops containing MC was approximately 1.3-fold higher than that of DSF eye drops. The opacification rate constant (k) of ICR/f rat instilled with DSF eye drops with or without MC was lower, and the initial time of opacification (τ) was longer than those of ICR/f rats instilled with saline. Furthermore, the k of ICR/f rats instilled with DSF eye drops with MC was lower than that of ICR/f rats instilled with DSF eye drops without MC. In conclusion, the analysis of kinetic parameters including k and τ using a one-exponential equation provided useful information for clarifying the anti-cataract effect of eye drops. ICR/f rats instilled with DSF eye drops using a low-substituted MC-based drug delivery system demonstrated a delay in cataract development, probably resulting from an increase in the retention of DSF eye drops on the cornea.     

Pharmacological treatment strategies in age-related cataracts.

Cataract is the major cause of blindness worldwide and at present the only approved treatment in many countries including the UK and USA is surgical removal of the lens. In other countries various anti-cataract drugs are available without proof of their efficacy. Research is continuing into the possible benefits of several groups of drugs and some vitamins. The first to be studied were sorbitol-lowering agents (aldose reductase inhibitors) based on the sorbitol hypothesis for diabetic cataract. Sorbitol-lowering agents have distinct effects in vitro and many of them delay the development of cataract in galactose-fed rats. A few delay cataract in diabetic rats but none have been proved effective in clinical trials, although these continue. Aspirin, paracetamol (acetaminophen) and ibuprofen delay diabetic cataract in rats, and have been shown to delay other experimental cataracts. Case-control studies from 3 continents indicate that these drugs, or at least aspirin, protect against cataract. Results of studies on all 3 drugs indicate a benefit even at low doses. Population-based studies did not identify any protection against early lens opacities but tiny opacities that do not impair vision are not a problem. Bendazac protects lens proteins in vitro and delays cataractogenesis in x-irradiated rats. In humans, it reached the clinical trial stage but most trials have been small and with subjective criteria of opacification. One objectively monitored trial suffered from a high drop-out rate. Other preparations studied less extensively include vitamins, aminoguanidine to prevent protein cross-linking in diabetes and agents designed to boost glutathione levels. It is probable that some agents which may delay or prevent cataract will be proved effective soon, and in the end there may be different drugs to delay cataract in different high risk groups. This is what might be expected of a multifactorial disease, although compounds that intervene in the final common pathways to cataract could have a broad efficacy.     

Investigations of ibuprofen and paracetamol binding to lens proteins to explore their protective role against cataract

There is evidence that ibuprofen and paracetamol can act as anti-cataract drugs. [14C]-Ibuprofen labelled at the methyl group of the propanoic acid moiety was synthesized. The labelled ibuprofen was found to bind non-covalently to alpha-crystallin but not to beta- and gamma-crystallin of the bovine lens. Labelled paracetamol binds to total lens soluble proteins. Both drugs penetrate into the lens cortex and nucleus within 24 hr. Affinity chromatographic studies suggest that the lipophilic isobutyl group of ibuprofen hinders binding to the lens proteins. Hence, in the light of weak binding of ibuprofen and paracetamol and strong binding of the ibuprofen analogue used in the affinity chromatography, it is suggested, in this paper, that the protection against cataract by these analgesics is possibly due to their metabolites interacting with the lens proteins.     

热休克蛋白27、70在老年性白内障晶状体上皮细胞中的表达

目的探讨热休克蛋白27（heat shock protein27,HSP27）和70（heat shock protein70,HSP70）在老年性白内障晶状体上皮细胞中的表达。方法采用免疫组织化学染色,检测老年性白内障晶状体前囊膜102例（其中皮质型36例,核型35例,后囊下型31例）,正常人5例晶状体上皮细胞中HSP27、HSP70的表达。结果 HSP27、HSP70在老年性白内障和正常人晶状体上皮细胞中表达有显著性差异,老年性白内障组各亚型间HSP27、HSP70的表达也有显著性差异。结论 HSP27、HSP70可能在老年性白内障的发生、发展中起重要作用,且在皮质型、核型、后囊下型白内障发生的作用机制可能不完全相同。     

Comparison of cell-permeable calpain inhibitors and E64 in reduction of cataract in cultured rat lenses.

E64, an inhibitor of calpain (EC 3.4.22.17) and other cysteine proteases, slows the rate of formation of cataract in cultured rat lenses. The purpose of this study was to determine (1) why E64, a charged compound with little cell permeability, was effective in reducing cataract in cultured lens and (2) whether uncharged more permeable protease inhibitors are more effective than E64 in preventing cataract. Results showed that E64 entered the lens, but only after the lens was treated with the calcium ionophore, A23187, or sodium selenite, both of which cause cataracts. Therefore, the uptake and subsequent effectiveness of E64 may be related to a generalized increase in membrane permeability during induction of cataract in culture. Three protease inhibitors, reported to have improved cell permeability, were compared with E64 for their ability to prevent cataracts in cultured lenses. cBz-ValPheH, calpain inhibitors I and II, are uncharged-aldehyde inhibitors of calpain. Calpain inhibitors I and II even at high concentrations were not effective at reducing lens opacity caused by calcium ionophore and were toxic to the lens. cBz-ValPheH, which is slightly toxic to the lens, was able to significantly reduce lens opacity induced by calcium ionophore. The presented data suggest that while E64 decreases cataract formation in cultured lens, the more cell permeable inhibitor, cBz-ValPheH, may have greater efficacy as an anticataract drug in vivo.     

金钗石斛的化学成分和药理作用研究进展

目的 对金钗石斛的化学成分和药理作用进行总结分析。方法 通过查阅中国期刊全文数据库（CNKI）和万方数据库2000—2013年的相关文献,对金钗石斛已报道的化学成分和药理作用进行了研究分析,总结阶段性进展和研究热点,并分析其原因。结果 金钗石斛主要化学成分为生物碱、多糖、倍半萜类、菲类、联苄类等,石斛碱是其特征性成分,主要有抗白内障、兴奋肠管、免疫调节、降血糖、抗肿瘤、抗氧化、抗疲劳等作用。结论 目前金钗石斛的研究仍侧重于化学成分与药理作用的研究,将来研究的重点可能为作用机制的明确和一些保健品的研发。