肾络通对肾间质纤维化实验大鼠病理及基质金属蛋白酶系统的影响

目的观察肾络通对实验大鼠肾间质纤维化的拮抗作用并探讨其作用机理。方法用单侧输尿管结扎方法复制大鼠肾梗阻模型,将其随机分为缬沙坦组、肾络通组、肾络通加缬沙坦组与模型组,并设假手术组。观察梗阻侧肾脏组织形态学改变、基质金属蛋白酶-1(MMP-1)及其基质金属蛋白酶抑制剂-1(TIMP-1)在蛋白及基因水平的表达并与假手术组比较。结果模型组及各治疗组与假手术组比较均呈现程度不同的病理损害,MMP-1、TIMP-1表达均有显著增高(P<0.05),且TIMP-1表达明显高于MMP-1表达。各治疗组与模型组比较,MMP-1表达无明显差异(P>0.05),TIMP-1表达却明显减少(P<0.05)。治疗各组间比较,TIMP-1表达肾络通加缬沙坦组明显低于缬沙坦组(P<0.05),其他组间均无明显差异(P>0.05)。结论输尿管梗阻后肾组织呈现程度不同的病理损害,可能与MMP-1/TIMP-1表达明显失衡有关。肾络通及缬沙坦对其有一定的抑制作用,且肾络通与缬沙坦联合用药,其作用比单一用药更强。     

中药凝胶贴膏基质处方的研究进展

中药凝胶贴膏临床使用方便、效果较好、无肝脏首过效应,是继口服、注射给药系统之后很有发展潜力的中药给药系统之一。对凝胶贴膏的基质处方组成及对其成型的作用进行详细综述,将基质处方组成分为骨架材料、增稠剂、保湿剂、交联剂和交联调节剂、填充剂、透皮促进剂和其他附加剂,分别介绍它们的概念、用量作用、常用种类、物化性质和研究进展,归纳基质处方设计的方法,最后提出目前基质研究存在的主要问题并对此研究领域进行展望,以期为中药凝胶贴膏的研究提供参考。     

喹硫平血药浓度监测中血清代用品的研究

考察以牛血清代替人血清制备标准曲线时,使用高效液相色谱法（HPLC）检测喹硫平血药浓度是否存在差异。人、牛血清制备的标准曲线在50.0～1000.0 ng·mL-1浓度范围内斜率存在差异,且在不同基质中患者血药浓度测得值有显著性差异（P＜0.01）。喹硫平在2种基质中的提取回收率也存在显著性差异（P＜0.01）。结果表明,HPLC法测定喹硫平血药浓度时以牛血清代替人血清作为空白基质检测存在差异性。     

腹主动脉瘤组织原纤维蛋白-1表达水平及其对患者生存结局的影响

目的 探讨腹主动脉瘤组织原纤维蛋白-1(FBN1)表达水平及其对患者生存结局的影响.方法 收集45例腹主动脉瘤(AAA)患者主动脉瘤组织和29例正常腹动脉血管壁组织,免疫组织化学染色检测组织基质金属蛋白酶(MMP9)、FBN1蛋白表达定位,蛋白质免疫印迹法检测组织FBN1、MMP9蛋白表达水平,实时荧光定量PCR检测组织FBN1、MMP9 mRNA表达水平.对45例AAA患者进行随访,分析FBN1表达与患者病理资料及生存结局的关系.结果 FBN1、MMP9主要表达于动脉瘤组织巨噬细胞或平滑肌细胞,主动脉瘤组织FBN1、MMP9蛋白阳性表达率86.7%、93.3%均高于正常动脉壁组织34.5%、48.3%(χ2=21.467,19.450,P<0.001).主动脉瘤组织FBN1、MMP9 mRNA相对表达量分别为(1.89 ±0.19)和(2.29 ± 0.31),正常动脉壁组织分别为(0.79 ±0.15)和(1.32 ±0.12),主动脉瘤组织FBN1、MMP9 mRNA相对表达量高于正常动脉壁组织(t=26.317,t=16.061,P<0.001),差异有统计学意义;主动脉瘤组织FBN1、MMP9蛋白表达量分别为(1.08 ±0.11)和(1.02 ±0.10),正常动脉壁组织分别为(0.29 ±0.06)和(0.39 ±0.07),主动脉瘤组织FBN1、MMP9蛋白表达量高于正常动脉壁组织(t=35.376,t=19.548,P<0.001).对照组FBN1与MMP9表达无相关性(P>0.05),AAA组FBN1与MMP9表达呈成正相关(r=0.861,P<0.05),差异有统计学意义.主动脉瘤破裂及瘤体直径>8.0 cm患者FBN1表达水平高于瘤体直径≤8.0 cm者,差异有统计学意义(P=0.047).FBN1阴性患者5年生存率为87.2%,FBN1阳性患者5年生存率为48.1%,FBN1阴性组5年生存率高于阳性组(χ2=17.081,P<0.05).结论 腹主动脉瘤组织FBN1表达显著升高,FBN1表达越高,患者生存率越低,FBN1可以作为AAA患者生存结局的评估指标之一.     

Fabrication and evaluation of Eudragit® polymeric films for transdermal delivery of piroxicam

The aims of this work were to develop and characterize the prolonged release piroxicam transdermal patch as a prototype to substitute oral formulations, to reduce side effects and improve patient compliance. The patches were composed of film formers (Eudragit^®) as a matrix backbone, with PVC as a backing membrane and PEG200 used as a plasticizer. Results from X-ray diffraction patterns and Fourier transform-infrared spectroscopy indicated that loading piroxicam into films changed the drug crystallinity from needle to an amorphous or dissolved form. Piroxicam films were prepared using Eudragit^® RL100 and Eudragit^® RS100 as film formers at various ratios from 1:0 to 1:3. Films prepared solely by Eudragit^® RL100 showed the toughest and softest film, while other formulations containing Eudragit^® RS100 were hard and brittle. Drug release kinetic data from the films fitted with the Higuchi model, and the piroxicam release mechanism was diffusion controlled. Among all formulation tested, Eudragit^® RL100 films showed the highest drug release rate and the highest drug permeation flux across human epidermal membrane. Increasing drug loading led to an increase in drug release rate. Eudragit^® can be used as a film former for the fabrication of piroxicam films.     

Effect of polymer type on characteristics of buccal tablets using factorial design

A two factor three level factorial design was used to investigate the effects of carbopol and cationic hydrophilic polymers which have a common use in buccal drug formulations. Statistical models with interaction terms were derived to evaluate influence of carbopol (X1) and chitosan (X2) on tablet disintegration (Y1) and dissolution (Y2), mechanical properties (Y3), swelling (Y4). Tablet disintegration studies were carried out using two different pH environments within buccal region pH limits and also two different commonly used dissolution methods for buccal tablets were also investigated to compare the effect of polymer type on dissolution. Polymer type and ratio affect the characteristics of the buccal tablets due to their different physicochemical behavior at buccal pH. Also significant variances between dissolution profiles for buccal tablets, using either USP Paddle or flow through cell methods were found. These results indicate that both polymer type and ratio as well as combination of them effects the drug behavior in different ways.     

依托考昔联合盐酸氨基葡萄糖治疗膝关节骨性关节炎的疗效分析

目的探讨依托考昔联合盐酸氨基葡萄糖治疗膝关节骨性关节炎的疗效。方法选取2016年2月至2017年8月在我院治疗的膝关节骨性关节炎患者112例,采用随机数字表法将患者分为依托考昔治疗组(n=37)、盐酸氨基葡萄糖治疗组(n=40)和联合治疗组(n=35),观察各组治疗疗效、WOMAC评分、关节滑液肿瘤坏死因子α(TNF-α)、基质金属蛋白酶-3(MMP-3)、MMP-9、MMP-13和不良反应。结果联合治疗组临床疗效优于依托考昔治疗组和盐酸氨基葡萄糖治疗组(P<0.05),其总有效率为94.29%;联合治疗组治疗后疼痛评分、僵硬评分、功能障碍评分及WOMAC总分分别为(11.57±2.82)分、(3.48±1.77)分、(30.05±8.96)分和(45.18±9.27)分,明显低于依托考昔治疗组和盐酸氨基葡萄糖治疗组(P<0.05);联合治疗组治疗后TNF-α、MMP-3、MMP-9和MMP-13分别为(30.12±9.22)pg/ml、(101.02±20.33)ng/ml、(32.28±10.05)ng/ml和(156.38±18.38)ng/ml,明显低于依托考昔治疗组和盐酸氨基葡萄糖治疗组(P<0.05);依托考昔治疗组和盐酸氨基葡萄糖治疗组治疗后疼痛评分、僵硬评分、功能障碍评分、WOMAC总分、TNF-α、MMP-3、MMP-9和MMP-13比较差异无统计学意义(P>0.05);三组不良反应发生率比较差异无统计学意义(P>0.05)。结论依托考昔联合盐酸氨基葡萄糖治疗膝关节骨性关节炎的疗效较好,同时可抑制TNF-α的释放和基质金属蛋白酶表达。     

Box-Behnken响应面法优化去氧氟尿苷缓释片处方及其体外释放机制研究

目的 响应面法优化去氧氟尿苷骨架片处方,并进行体外释放机制研究。方法 以羟丙甲纤维素(HPMC K4M)为骨架材料,结合其他辅料混合均匀,以直接压片法制备去氧氟尿苷骨架缓释片。通过Box-Behnken响应面法(Box-Behnken design-response surface methodology, BBD-RSM)对处方进行优化,研究优化处方的体外释药规律,并进行数学模型拟合。结果 优化处方的去氧氟尿苷骨架缓释片体外释放性能良好,可持续释药24h,药物释放符合Ritger-peppas模型。结论 通过BBD-RSM建立的模型可用于去氧氟尿苷骨架缓释片的处方优化,优化处方达到去氧氟尿苷缓释骨架片设计要求。     

Trabecular meshwork ECM remodeling in glaucoma: could RAS be a target?

Introduction: Disturbances of extracellular matrix (ECM) homeostasis in trabecular meshwork (TM) cause increased aqueous outflow resistance leading to elevated intraocular pressure (IOP) in glaucomatous eyes. Therefore, restoration of ECM homeostasis is a rational approach to prevent disease progression. Since renin-angiotensin system (RAS) inhibition positively alters ECM homeostasis in cardiovascular pathologies involving pressure and volume overload, it is likely that RAS inhibitors reduce IOP primarily by restoring ECM homeostasis.

Areas covered: Current evidence showing the presence of RAS components in ocular tissue and its role in regulating aqueous humor dynamics is briefly summarized. The role of RAS in ECM remodeling is discussed both in terms of its effects on ECM synthesis and its breakdown. The mechanisms of ECM remodeling involving interactions of RAS with transforming growth factor-β, Wnt/β-catenin signaling, bone morphogenic proteins, connective tissue growth factor, and matrix metalloproteinases in ocular tissue are discussed.

Expert opinion: Current literature strongly indicates a significant role of RAS in ECM remodeling in TM of hypertensive eyes. Hence, IOP-lowering effect of RAS inhibitors may primarily be attributed to restoration of ECM homeostasis in aqueous outflow pathways rather than its vascular effects. However, the mechanistic targets for RAS inhibitors have much wider distribution and consequences, which remain relatively unexplored in TM.