As the most prevalent disease globally and with a lack of efficient therapeutic drugs, there is a need for novel strategies to treat osteoarthritis (OA). One approach being explored is the usage of biodegradable polymers as drug-delivery systems for OA treatment. However, a limitation of these polymeric drug carriers is that they do not possess therapeutic efficacy themselves. To address this issue, a new strategy has been developed using an aspirin-like oligomer called poly (salicylic acid) (PSA). The oligomer is synthesized through the self-esterification of salicylic acid (SA), which is a non-steroidal anti-inflammatory drug (NSAID) commonly used to relieve pain and inflammation associated with OA. Self-assembled PSA nanoparticles (PSA NPs) possess a distinctive capability to dynamically modulate the release rate of SA through the manipulation of their morphology. Crucially, SA, as the degradation product of the PSA NPs, has been substantiated to possess a demonstrated capability for capturing reactive oxygen species (ROS). In vitro studies have demonstrated the negligible toxicity of PSA NPs against SW1353 cells. Moreover, in vivo results have indicated that intra-articular injection of PSA NPs resulted in prolonged joint retention and significant alleviation of OA lesions in mice. Both in vitro and in vivo investigations have proved the capacity of PSA NPs to attenuate inflammation and restore the balance of cartilage extracellular matrix (ECM) metabolism through the inhibition of COX-2 and NF-κB p65 expressions. These compelling results suggest that the PSA NPs hold promising potential as an effective therapeutic strategy for OA.

Cholinesterase and monoamine oxidase are potential targets for the therapy of Alzheimer's disease. A series of novel AP2238-clorgiline hybrids as multi-target agents were designed, synthesized and investigated in vitro for their inhibition of cholinesterases and monoamine oxidases. Many compounds displayed balanced and good inhibitory activity against AChE, BuChE and MAO-B with an obvious selective inhibitory effect on MAO-B. Among them, Compound 5l showed the most balanced potency to inhibit ChEs (eeAChE: IC50 = 4.03 +/- 0.03 mu M, eqBuChE: IC50 = 5.64 +/- 0.53 mu M; hAChE: IC50 = 8.30 +/- 0.04 mu M, hBuChE: IC50 = 1.91 +/- 0.06 mu M) and hMAO-B (IC50 = 3.29 +/- 0.09 mu M). Molecular modeling and kinetic studies showed that 5l was a mixed inhibitor for both AChE and BuChE, and a competitive MAO-B inhibitor. Compound 5l exhibited no toxicity to PC12 and BV-2 cells at 12.5 mu M and no acute toxicity at a dosage of 2500 mg/kg. Moreover, 5l can improve the memory function of mice with scopolamine-induced memory impairment and have an excellent ability to cross the blood-brain barrier. Overall, these findings suggested that compound 5l could be deemed as a promising, balanced multi-target drug candidate against Alzheimer's disease.

目的 探讨复方山慈菇对人乳腺癌MDA-MB-231细胞裸鼠移植瘤生长的抑制作用及其潜在的作用机制.方法 将人乳腺癌MDA-MB-231细胞裸鼠移植瘤模型随机分为模型组、阳性对照多柔比星(doxorubicin,DOX)组和复方山慈菇醇提物(compound cremastra appendiculata ethanol extraction,CCAEE)高剂量组(1.8 g/kg)以及低剂量组(0.9 g/kg),每组5只.按照分组连续灌胃给药21d后,处死裸鼠并计算各组裸鼠移植瘤体积、重量和抑瘤率.采用TCMSP 2.3数据库选出复方山慈菇有效成分及其对应的作用靶点,OMIM、GeneCards 5.14、DrugBank 5.1.10、TTD数据库筛选关键靶点并利用STRING 11.5数据库构建蛋白质相互作用(PPI)网络,然后筛选核心靶点,以构建"药物-成分-靶点"网络并筛选出核心有效成分.利用Metascape 3.5平台进行GO和KEGG富集分析.结果 各组荷瘤裸鼠分别给药处理21d后,与模型组比较,DOX组和CCAEE高、低剂量组裸鼠移植瘤体积、重量均明显减小(均P<0.05),抑瘤率分别为89.67%、67.39%和43.48%.通过网络药理学分析获得复方山慈菇有效成分27个,抗乳腺癌关键靶点108个,其中核心靶点23个,主要包括TP53、MAPK3、MAPK1、RELA、AKT1、FOS、ESR1、TNF、IL6、MAPK14等;核心有效成分5个,分别为槲皮素、山柰酚、β-谷甾醇、2-甲氧基-9,10-二氢菲-4,5-二醇、去氧鬼臼毒素.GO和KEGG富集分析显示复方山慈菇主要通过激素调节等生物过程以及PI3K-AKT、MAPK等信号通路发挥抗乳腺癌作用.结论 复方山慈菇能抑制人乳腺癌移植瘤生长,其可能通过槲皮素、山柰酚等核心有效成分作用于TP53等核心靶点及PI3K-AKT、MAPK等信号通路而发挥抗乳腺癌作用.

Celastrol has been identified as a potential candidate for anticancer drug development. In this study, 28 novel celastrol derivatives with C‐6 sulfhydryl substitution and 20‐substitution were designed and synthesized, and their antiproliferative activity against human cancer cells and non‐malignant human cells was evaluated, with cisplatin and celastrol being used as controls. The results showed that most of the derivatives had enhanced in vitro anticancer activity compared to the parent compound celastrol. Specifically, derivative 2f demonstrated the most potent inhibitory potential and selectivity against HOS with an IC50 value of 0.82 μM. Our study provides new insights into the structure–activity relationship of celastrol and suggests that compound 2f may be a promising drug candidate for the treatment of osteosarcoma.

Though palbociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor has been approved for treating breast cancer, two major clinical challenges remain: (i) Triple-negative breast cancer (TNBC) appears to be more resistant to palbociclib, and (ii) Palbociclib-induced senescence-associated secretory phenotype (SASP) has a pro-tumorigenic function. Here we report that combining palbociclib with the STAT3 inhibitor nifuroxazide uncouples SASP production from senescence-associated cell cycle exit. Moreover, we identified nifuroxazide as a CDK2 inhibitor that synergistically promotes palbociclib-induced growth arrest and senescence in TNBC cells. In vitro, the combination of nifuroxazide with palbociclib further inhibited the TNBC cell proliferation and enhanced palbociclib-induced cell cycle arrest and senescence. The modulation of palbociclib-induced SASP by nifuroxazide was associated with the reduction of phosphorylated-STAT3. Nifuroxazide also blocks SASP-dependent cancer cell migration. Furthermore, thermal shift assay and molecular docking of nifuroxazide with STAT3 and CDK2 revealed that it binds to their active sites and acts as a potent dual inhibitor. In vivo, the combination of nifuroxazide with palbociclib suppressed 4T1 tumor growth and lung metastasis. Our data suggest that nifuroxazide enhances the anticancer effects of palbociclib in TNBC by uncoupling SASP production from senescence-associated cell cycle exit and inhibiting CDK2 to promote tumor senescence.

目的:采用网络药理学和分子对接方法探讨积雪草酸(AA)调控铁死亡的作用机制,并在脂多糖(LPS)诱导的炎症巨噬细胞模型上进行初步验证.方法:检索SwissTargetPrediction、SEA Search Server、HERB等9个数据库获得AA相关靶点,通过FerrDb 2.0、GeneCards 5.14、KEGG、NCBI等数据库获取铁死亡相关靶点,利用Venny 2.1.0在线工具映射获得AA和铁死亡的交集靶点.采用DAVID 6.9数据库对交集靶点进行GO和KEGG富集分析,String 11.5数据库和Cytoscape 3.9.1软件构建蛋白质相互作用(PPI)网络,并采用CytoHubba插件筛选出核心靶点.最后采用Autodock Tool 1.5.7软件将AA与核心靶点进行分子对接,Pymol 4.2软件对分子对接结果可视化.构建LPS诱导的RAW264.7小鼠巨噬细胞炎症模型,激光共聚焦法检测AA对炎症巨噬细胞内脂质活性氧(lipidROS)荧光强度的影响;细胞免疫荧光法检测AA和Akt激活剂SC79对谷胱甘肽过氧化物酶4(GPX4)、p-Akt表达的影响.结果:网络药理学分析共筛选出203个AA与铁死亡交集靶点.富集分析结果显示,AA可能通过AKT1等核心靶点介导PI3K/Akt等信号通路调控铁死亡;分子对接结果显示,AA与AKT1等核心靶点均能稳定结合.在LPS诱导的巨噬细胞,AA明显降低巨噬细胞lipid ROS荧光强度,增强GPX4而减弱p-Akt荧光表达(与LPS组比较,P＜0.01);SC79使AA增强GPX4表达的作用明显减弱(与单用AA比较,P＜0.01).结论:AA抑制炎症巨噬细胞铁死亡,机制可能与负调控Akt活性有关.

以广西医科大学药学专业为例,探析了当前药学专业创新创业教育国内现状以及存在问题,主要表现为创新创业教育与专业教育、思想政治教育融合不足、师资队伍能力有待提升、实践教学与平台有待加强等.本文提出以创新创业教育为突破口推动专业综合改革,通过人才培养方案修订与课程体系改革、师资队伍建设、课堂教学改革、实践平台搭建和实践育人体系构建等一系列举措,形成具有地方医学院校特色的"思专创"三位一体药学人才培养体系,为药学专业高等教育改革提供参考.

目的:基于网络药理学和巨噬细胞炎症模型探讨积雪草酸(AA)抗动脉粥样硬化(AS)的作用机制.方法:首先,通过Swiss Target Prediction、CTD、GeneCards数据库获取AA相关靶点,GeneCards、TTD数据库获取AS相关靶点,之后通过Venny 2.1.0在线工具映射获得AA与AS的交集靶点.采用String 11.5数据库和Cytoscape 3.7.2软件构建交集靶点的蛋白相互作用(PPI)网络图并筛选出核心靶点;通过David 6.8数据库对交集靶点进行GO和KEGG通路富集分析,并通过微生信在线工具对富集结果进行可视化.最后采用Cytoscape3.7.2软件构建出"药物-靶点-疾病-通路"网络模型图.构建脂多糖(LPS)诱导的RAW264.7小鼠巨噬细胞炎症模型,通过ELISA法检测TNF-α释放水平,Annexin V-APC/7-AAD双染色法流式细胞术及Western blotting检测细胞凋亡率及凋亡相关蛋白表达,验证AA对巨噬细胞炎症和凋亡的影响.结果:网络药理学预测共获得AA抗AS的潜在作用靶点84个,GO和KEGG分析结果显示AA抗AS机制可能与调控TNF、NOD样受体、凋亡及PPAR等信号通路有关.细胞实验结果显示,与LPS组比较,AA高、低剂量组TNF-α水平降低,细胞凋亡率和Bax、Cyt C蛋白表达进一步提高,而Bcl-2蛋白表达下降(P＜0.05或P＜0.01).结论:AA可通过多靶点、多通路发挥抗AS作用,诱导巨噬细胞凋亡和抗炎为其作用机制之一.

Herein, we present the facile design and construction of a nanodrug system integrating targeted drug delivery and synergistic chemo-photothermal antitumor activity. MoS2 nanosheets were synthesized and modified by ανβ3 integrin binding peptide (Arg-Gly-Asp, RGD) using lipoic acid functionalized polyethylene glycol (LA-PEG-COOH), forming a well dispersed and targeted delivery nanocarrier. Further, covalent coupling of antitumor drug, thiolated doxorubicin (DOX) via disulfide linkage resulted in a novel nanodrug, RGD/MoS2/DOX. The prepared nanocarrier showed favorable stability, biocompatibility and photothermal conversion efficiency. Fluorescence imaging revealed that Hela cells could endocytose far more nanodrug than H9c2 normal myocardial cells due to the targeted delivery characteristic. Particularly, GSH-induced disulfide bond cleavage facilitated the effective release of DOX from the nanodrug in the tumor microenvironment. The survival rate of Hela cells incubated with the nanodrug for 48 h was 22.2 ± 1.2%, which dramatically reduced to 8.9 ± 1.4% in combination with 808 nm NIR irradiation, demonstrating powerful photothermal induced tumor-killing efficacy. In contrast, the survival rates of H9c2 cells treated by the nanodrug and free DOX were 68.5 ± 2.6% and 6.7 ± 2.6%, respectively, an indication of the notably alleviated cardiotoxicity of the designed nanodrug. The cell apoptosis experiment further verified the synergistic chemo-photothermal effect, thus paving a way toward design of high-efficiency and low-toxicity antitumor nanodrug.

目的:探讨环加氧酶-2(COX-2)抑制剂塞来昔布联合5-脂加氧酶(5-LO)抑制剂齐留通对ApoE-/-小、鼠动脉粥样硬化(AS)病变的影响及机制.方法:雄性ApoE-/-小鼠随机分成AS模型组、塞来昔布组(80 mg/kg/d)及塞来昔布联合齐留通(400 mg/kg/d)组(高脂饲料喂养),野生型雄性C57BL/6J小鼠为正常对照组(普通饲料喂养),每组12只.每日灌胃给药18周后,取血测定血脂水平,小动物B超下测量主动脉弓斑块面积比(％)、主动脉全长油红O染色测量阳性斑块面积比(％)及主动脉根部切片苏木精—伊红(HE)染色测量斑块面积比(％)和内中膜厚度(IMT)并观察AS病理形态学改变,ELISA测定主动脉匀浆花生四烯酸(AA)代谢产物前列腺素E2(PGE2)和白三烯(LTs)[包括白三烯B4(LTB4)和半胱氨酰白三烯(CysLTs)]含量.结果:与正常对照组比较,AS模型组小鼠血清总胆固醇(TC)、低密度脂蛋白(LDL-C)和高密度脂蛋白(HDL-C)水平明显升高(P＜0.05或P＜0.01),但总甘油三酯(TG)水平无明显改变(P＞0.05);塞来昔布组及塞来昔布联合齐留通组血脂各指标与AS模型组比较,差异无统计学意义(P＞0.05).小动物B超、主动脉全长油红O染色及主动脉根部切片HE染色病理学观察及定量检测结果均表明AS模型组小鼠形成了明显的主动脉AS病变,塞来昔布加重AS病变,塞来昔布联合齐留通减轻塞来昔布加重的AS病变(均P＜0.05或P＜0.0l).AS模型组小鼠主动脉匀浆PGE2、LTB4和CysLTs含量均较正常对照组显著升高(P＜0.01);与AS模型组相比,塞来昔布组小鼠主动脉匀浆PGE2含量显著降低,而LTB4和CysLTs含量则显著升高(P＜0.01);与塞来昔布组相比,塞来昔布联合齐留通组主动脉匀浆PGE2含量无明显改变(P＞0.05),但LTB4和CysLTs含量明显降低(P＜0.01).结论:塞来昔布上调LTs加重ApoE-/-小鼠AS病变的作用可被5-LO抑制剂齐留通逆转.

目的:探讨复方山慈菇醇提物对人三阴性乳腺癌(TNBC)MDA-MB-231细胞增殖与凋亡的影响.方法:将人乳腺癌MDA-MB-231细胞分为溶剂对照组和复方山慈菇醇提物组,0.1％ DMSO或不同浓度的复方山慈菇醇提物作用于MDA-MB-231细胞24 h、48 h后,CCK-8法检测细胞活性;Hoechst33342染色法观察细胞形态学变化;Annexin V-APC/7-AAD双染色流式分析检测细胞凋亡率;Western blot检测凋亡相关蛋白Bcl-2、Bax和Caspase-3的表达.结果:复方山慈菇醇提物可浓度和时间依赖性地抑制MDA-MB-231细胞的增殖(P＜0.05),24 h、48 h的IC50分别为0.51 mg生药/mL和0.26 mg生药/mL;0.25 mg生药/mL、0.5mg生药/mL、1.0mg生药/mL复方山慈菇醇提物处理24 h后,Hoechst33342染色显示细胞出现凋亡样变化;流式细胞术检测结果表明,与溶剂对照组比较,复方山慈菇醇提物可浓度依赖性地增加MDA-MB-231细胞凋亡率(P＜0.05);Western blot法显示,与溶剂对照相比,0.5mg生药/mL复方山慈菇醇提物组Bax、Caspase-3蛋白表达升高,Bcl-2蛋白表达下降(均P＜0.05).结论:复方山慈菇可体外抑制人乳腺癌MDA-MB-231细胞的增殖,机制可能与其下调Bcl-2及上调Bax、Caspase-3蛋白表达而诱导凋亡有关.

目的:研究积雪草酸(AA)体内外抗肝癌效应及其凋亡机制.方法:将人肝癌SMMC-7721细胞分为溶剂(0.1％DMSO溶剂)对照组和不同浓度(20 μmol/L、30 μmol/L、40 μmol/L、50 μmol/L、60 μmol/L) AA组,作用于SMMC-7721细胞24 h后,采用CCK-8法检测细胞活性,Annexin V-APC/7-AAD双染色流式分析检测细胞凋亡率,JC-1染色检测细胞线粒体膜电位,同时采用Western blotting检测线粒体凋亡相关蛋白的表达.建立SMMC-7721细胞裸鼠皮下移植瘤模型,分为对照组、AA 50 mg/kg组和AA 100 mg/kg组,每组5只,观察AA灌胃给药21d后移植瘤的生长情况.结果:AA浓度依赖性地抑制SMMC-7721细胞增殖(IC50=38.31μmol/L)并促使细胞产生凋亡样改变.与溶剂对照组相比,AA 20 μmol/L组、AA 40μmol/L组、AA 60 μmol/L组均可提高SMMC-7721细胞凋亡率,并降低细胞线粒体膜电位(均P＜0.01),具有一定的浓度依赖性;此外,AA 40 μmol/L组明显上调Bax、Cyt-C和Cleaved-Caspase-3蛋白的表达,下调Bcl-2蛋白的表达(P＜0.05或P＜0.01),但对p53蛋白表达无明显影响(P＞0.05).AA 50 mg/kg组和AA 100 mg/kg组给药第14、第21天时的肿瘤体积明显小于对照组,给药第21天时的肿瘤质量小于对照组(均P＜0.01).结论:AA具有体内外抗肝癌作用,其机制可能与其诱导非p53依赖的线粒体途径的凋亡有关.

Background and aims: COX-2-selective inhibitors have been associated with an increased risk of cardiovascular complications, and their impact on atherosclerosis ( AS) remains controversial. The proinflammatory COX-2 and 5-LO pathways both play essential roles in AS and related cardiovascular diseases. Previous clinical studies have provided evidence of the ability of COX-2-selective inhibitors to shunt AA metabolism from the COX-2 pathway to the 5-LO pathway. In this study, the effects of celecoxib, a selective COX-2 inhibitor, on AS and the COX-2 and 5-LO pathways were investigated in vivo and in vitro. Methods: Male ApoE(-/-) mice fed a western-type diet for 18 weeks and cultured mouse RAW264.7 macrophages stimulated with 1 mu g/mL LPS for 24 h were used in this study. Results: In ApoE(-/-) mice, intragastric administration of celecoxib ( 80 mg/kg/d) for 18 weeks significantly increased aortic atherosclerotic lesion area but had no effect on hyperlipidemia. In addition, celecoxib significantly lowered TNF-a and PGE2 levels but increased both LTB4 and CysLTs levels in aortic tissues. In LPS-stimulated RAW264.7 macrophages, pretreatment with 8 mu mol/L celecoxib for 1 h significantly lowered the TNF-a, NO, and PGE2 levels but increased the LTB4 and CysLTs levels. Celecoxib also decreased the protein and mRNA expression of COX-2 but increased the expression of 5-LO and LTC4S in both ApoE(-/-) mouse aortic tissues and LPSstimulated RAW264.7 macrophages. Conclusion: The COX-2-selective inhibitor celecoxib can aggravate atherogenesis, an effect that may be related to upregulation of LTs via a 5-LO pathway shunt.

BACKGROUND: The rare earth elements (Res) have multiple bio-activities and some extent neurotoxicity, Because of their distinct physical and chemical properties. The studies on neuromuscular junction and sympathet ic ganglia have shown that some Res, such as lanthanum(La), gadolinium (Gd),etc, exert considerable effects on synaptic transmission, but the effects and mechanism of Samarium on synaptic transmission are still unknown.OBJECTIVE: To investigate the effects and impossible mechanism of Samarium Chloride (SmCl3) on the nicotinic transmission in the isolated sympathetic ganglia, superior cervical ganglion (SCG) of rats.DESIGN: Controlled experimental study based on cells.SETTING: Department of Pharmacology, Guangxi Medical University. MATERIALS: Totally 40 adult Wistar rats (weighing 250-300 g) of either sex, provided by the Experimental Animal Center of Guangxi Medical University, were used in this study. SmCl3 was made by the chlorination of Samarium Oxide with purity 99.5% and relative molecule mass 348.7, presented by Professor Liu Da-yuan, Guangxi Medical University. Acetylcholine chloride (Ach) and carbachol (Carb) were purchased from Sigma.METHODS: The experiment was completed at the neuropharmacology lab of the experimental center of Guangxi Medical University from September 2001 to December 2002. After sacrificing animals by acute exsanguination,SCG together with their preganglionic nerve trunks were isolated rapidly,then transferred to the recording chamber, the preganglionic nerve trunk was drawn into a suction electrode for orthodromic stimulation. The ganglia were superfused continuously with a Krebs solution, saturated with 950 mL/L 02 and 5mL/L CO2, pH 7.4±0.05, (34±0.5) ℃.The fiber containing glass microelectrodes filled with 3 mol/L KC1 (30-60 MΩ tip resistance) were used to impaled cells and do intracellular recording. The fast excitatory postsynaptic potentials (FEPSPs) were evoked in SCG neurons by single pulse stimulations (0.2-0.5 Hz, 0.5-1.0 ms, 2-10 V)on preganglionic nerve trunk. The remarkable membrane depolarization would be recorded in SCG neurons by superfusing ganglia with exogenous Ach (0.1 mmol/L) or Carb(0.1 mmol/L) for 30-60 s. The effects of 1×(10-7-10-4) mol/L SmCl3 on FEPSPs, membrane potentials, membrane resistance, exogenous Ach and Carb-induced membrane depolarization of SCG neurons were investigated in this experiment.The effects of SmCl3 on the facilitation of high Ca2+ (10 mmol/L ) on FEPSPs were also be observed, namely, first superfusing the ganglia with high Ca2+ (10 mmol/L)to facilitate FEPSPs, then superfusing the ganglia with Ca2+(10 mmol/L)contained SmCl3. All the drugs were solved in Krebs solution or improved Krebs solution and applied to ganglia by superfusion in known concentration.The bioelectricity difference before and after the drug superfusion were analyzed by paired Student's t test.MAIN OUTCOME MESURES: ①Effects of SmCl3 on FEPSPs.②Effects of SmCl3 on membrane potentials and membrane resistances. ③Effects of SmCl3 on exogenous Ach and Carb-induced membrane depolarization. ④Effects of SmCl3 on the facilitation of high Ca2+ (10 mmol/L ) on FEPSPs.RESULTS: ① 1 ×(10-7-10-4)mol/L SmCl3 could reversibly depressed the FEPSPs of rats SCG neurons [the amplitude inhibitory percentage of FEPSPs of l×10-4, 1×10-5, 1×10-6, 1×107 mol/L SmCl3 was (49.78±13.85)%(n=20),(39.05±4.05)%(n=10),(29.83±9.73)%(n=10)and (16.30±2.16)%(n=10)respectively (P ＜ 0.05-0.01)].1×10-4 mol/L SmCl3 could chang Aps into FEPSPs (n=5).②The membrane depolarization induced by Ach (n=5) and Carb (n=7) were not significantly changed by 1×10-4 mol/L SmCl3(P ＞ 0.05).③The membrane potential and membrane resistance were not significantly altered by 1×(10-7-10-4)mol/L SmCl3(n=67), P ＞ 0.05. ④1×10-4 mol/L SmCl3 could antagonized the facilitation of high Ca2+ (10 mmol/L ) on FEPSPs (n=5), P ＜ 0.01.CONCLUSION: SmCl3 can depresses nicotinic transmission in rats sympathetic ganglia by presynaptic mechanisms, perhaps due to its inhibition on Ca2+ influx.

目的:分析复方鸡骨草胶囊对四氯化碳、D-半乳糖胺所致小鼠急性化学性肝损伤的保护作用。方法:实验于2006-01/03在广西医科大学药学院药理学教研室实验室完成。取健康成年昆明种系小鼠144只,按随机数字表法分为12组,每组12只。分为2个实验,四氯化碳和D-半乳糖胺肝损伤实验均设6个组,正常对照组、模型组、鸡骨草胶囊组、复方鸡骨草胶囊12.96g/kg,6.48g/kg,3.24g/kg组。鸡骨草胶囊组和复方鸡骨草胶囊12.96g/kg,6.48g/kg,3.24g/kg组分别灌胃给予鸡骨草胶囊14.47g/kg和复方鸡骨草胶囊（鸡骨草胶囊的升级产品,由鸡骨草、茵陈、栀子、三七、牛黄、白芍等多种中草药配伍组成）12.96,6.48,3.24g/kg,其余各组小鼠灌胃给予等量生理盐水,灌胃1次/d,连续5d。5d后除正常对照组外,其余各组腹腔注射1g/L的四氯化碳/花生油溶液10mL/kg或腹腔注射D-半乳糖胺800mg/kg,禁食,16h后测定血清谷丙转氨酶和谷草转氨酶活性,观察肝脏组织病理学改变。结果:144只小鼠全部进入结果分析,无脱失。四氯化碳和D-半乳糖胺肝损伤2个实验中,鸡骨草胶囊组和复方鸡骨草胶囊12.96g/kg,6.48g/kg组小鼠的血清谷丙转氨酶和谷草转氨酶活性显著低于模型组（P＜0.05～0.01）,鸡骨草胶囊和复方鸡骨草胶囊各剂量组肝组织受损程度显著轻于模型组（P＜0.05～0.01）,复方鸡骨草胶囊各剂量与鸡骨草胶囊的效应比较,差异无显著性意义（P＞0.05）。结论:复方鸡骨草胶囊对四氯化碳、D-半乳糖胺引起的小鼠急性化学性肝损伤均有明显的保护作用,保肝效应和鸡骨草胶囊相当。

目的:探讨高血压患者昼夜血压呈杓型、非杓型分布时肾素-血管紧张素-醛固酮系统的昼夜波动特征及其与靶器官损害的关系.方法:①选择2002-01/2003-12在柳州市人民医院心血管内科住院的高血压患者63例.均对实验目的知情同意.根据血压昼夜节律分型情况将63例患者分为杓型组(n=30,下降≥10%但＜20%者为杓型,20%者为超杓型)和非杓型组[n=33,夜间收缩压及(或)舒张压较日间下降＜10%].②采用放射性免疫方法测定各组患者24 h内3个时间段(次日晨8:00空腹、下午16:00及夜间24:00)的血浆肾素、血管紧张素、醛固酮的水平.采用超声心动图测量左室舒张末期内径、舒张期室间隔厚度及左室后壁厚度,并测定肾功能、24 h尿蛋白定量分析、眼底检查,以了解靶器官损害程度.③应用方差分析方法比较两组间的基本特征,计量资料采用t检验.结果:高血压患者63例均进入结果分析.①非杓型组8:00和24:00血浆肾素、醛固酮水平明显高于杓型组(P＜0.05),16:00血浆血管紧张素水平明显高于杓型组(P＜0.05).两组醛固酮、血管紧张素日间和夜间的波动较大,而肾素的昼夜波动不大.②非杓型组患者左室舒张末期内径、舒张期室间隔厚度、24 h尿蛋白定量明显大于或高于杓型组(P＜0.01).结论:①昼夜血压呈杓型与非杓型分布患者血液中肾素和醛固酮的水平昼夜节律特征有所不同,体液因素是调控人体血压水平及其昼夜节律的非常重要的环节.②血压呈非杓型分布的高血压患者发生心脑肾等靶器官并发症的危险性高于杓型高血压患者.