复方丹参片联合多奈哌齐治疗阿尔茨海默病的临床疗效研究

目的探讨复方丹参片联合多奈哌齐治疗阿尔茨海默病(AD)的安全性和有效性。方法选取广西壮族自治区江滨医院AD患者共100例,随机数字表法分为观察组和对照组,每组50例。对照组给予多奈哌齐治疗,观察组给予复方丹参片联合多奈哌齐治疗。观察组与对照组治疗前、治疗后1个月、治疗后3个月的简易精神状态量表(MMSE)评分、AD认知功能评定量表(ADAS-cog)评分、日常生活能力量表(ADL)评分、血清谷氨酸(Glu)水平、血清天冬氨酸(Asp)水平,均采用重复测量设计的方差分析。统计不良反应发生率。结果 (1)不同时间点间的MMSE评分、ADAS-cog评分、ADL评分、血清Glu水平、血清Asp水平有差异(P<0.05)。(2)观察组与对照组的MMSE评分、ADAS-cog评分、ADL评分、血清Glu水平、血清Asp水平有差异(P<0.05),观察组与对照组比较MMSE评分较高,ADAS-cog评分、ADL评分、血清Glu水平、血清Asp水平较低。(3)观察组与对照组的MMSE评分、ADAS-cog评分、ADL评分、血清Glu水平、血清Asp水平变化趋势有差异(P<0.05)。观察组和对照组不良反应发生率比较,差异无统计学意义(P<0.05)。结论复方丹参片联合多奈哌齐治疗AD的效果确切,其机制可能与抑制兴奋性氨基酸表达有关。

Scutellarin prevents acute alcohol-induced liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and inhibiting inflammation by regulating the AKT,p38 MAPK/NF-κB pathways

Alcoholic liver disease(ALD)is the most frequent liver disease worldwide,resulting in severe harm to personal health and posing a serious burden to public health.Based on the reported antioxidant and anti-inflammatory capacities of scutellarin(SCU),this study investigated its protective role in male BALB/c mice with acute alcoholic liver injury after oral administration(10,25,and 50 mg/kg).The results indicated that SCU could lessen serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels and improve the histopathological changes in acute alcoholic liver;it reduced alcohol-induced malondialdehyde(MDA)content and increased glutathione peroxidase(GSH-Px),catalase(CAT),and superoxide dismutase(SOD)activity.Furthermore,SCU decreased tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1βmessenger RNA(mRNA)expression levels,weakened inducible nitric oxide synthase(iNOS)activity,and inhibited nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome activation.Mechanistically,SCU suppressed cytochrome P450 family 2 subfamily E member 1(CYP2E1)upregulation triggered by alcohol,increased the expression of oxidative stress-related nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)pathways,and suppressed the inflammation-related degradation of inhibitor of nuclear factor-κB(NF-κB)-α(IκBα)as well as activation of NF-κB by mediating the protein kinase B(AKT)and p38 mitogen-activated protein kinase(MAPK)pathways.These findings demonstrate that SCU protects against acute alcoholic liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and suppressing inflammation by regulating the AKT,p38 MAPK/NF-κB pathways.

Mechanistic insights into the novel glucose-sensitive behavior of P(NIPAM-co-2-AAPBA)

A glucose-sensitive polymer,poly(N-isopropylacrylamide-co-2-acrylamidophenylboronic acid)(P(NIPAM-co-2-AAPBA)),was synthesized by reversible addition fragmentation chain transfer(RAFT)copolymerization.Addition of glucose results in reduced solubility and hence increased turbidity,rather than the normal increase in solubility(decreased turbidity)observed for other PBA-based glucose-sensitive polymers.The novel glucose-sensitive behavior is explained by a new mechanism,in which glucose acts as an additive and depresses the lower critical solution temperature(LCST)of the polymer,instead of increasing solubility by increasing the degree of ionization of the PBA groups.Experimental and theoretic analysis for the influence of glucose on the thermal behavior of P(NIPAM-co-2-AAPBA)reveals that glucose depresses the LCST of P(NIPAM-co-2-AAPBA)copolymers in a two-stage manner,a fast decrease at low glucose concentrations followed by a slow decrease at high glucose concentrations.For low glucose concentrations,the binding of glucose with PBA groups on the polymer chain increases the number of glucose molecules proximal to the polymer which influences the thermal behavior of the polymer,causing a rapid decrease in LCST.Importantly,the transition occurs at a glucose concentration equal to the reciprocal of the binding constant between PBA and glucose,thus providing a novel method to determine the binding constant.Other saccharides,including mannose,galactose and fructose,also depress the LCST of P(NIPAM-co-2-AAPBA)copolymer in the same way.

Synthesis and biological evaluation of 3-amino-2-pyrones as selective cyclooxygenase-1(COX-1) inhibitors

Received 2 December 2012 Received in revised form 21 December 2012 Accepted 27 December 2012 Available online 4 February 2013