破壁灵芝孢子粉与雌二醇抗肝纤维化的比较研究

目的：通过破壁灵芝孢子粉和雌二醇对CCl4诱导的肝纤维化大鼠肝组织转化生长因子β1（TGF-β1）影响的实验研究,比较破壁灵芝孢子粉和雌二醇的作用效果。方法：使用CCl4诱导大鼠肝纤维化动物模型,分别给予雌二醇和高低剂量的破壁灵芝孢子粉处理。通过免疫组化染色半定量分析TGF-β1的表达状况。结果：TGF-β1雌二醇组与破壁灵芝袍子粉高剂量组之间无统计学差异（P〉0.05）,均值小于低剂量组高于对照组,其他各组间两两比较均有统计学差异（P〈0.05）。结论：破壁灵芝袍子粉高剂量组与雌二醇在抗肝纤维化中的作用效果接近,低剂量组作用效果低于雌二醇组。     

破壁灵芝孢子粉与雌二醇对肝功影响的比较研究

目的:通过比较破壁灵芝孢子粉与雌二醇对肝纤维化生化指标的影响,为治疗肝硬化提供参考.方法:CCl4诱导大鼠肝纤维化动物模型,分别观察破壁孢子粉与雌二醇对大鼠肝纤维化形成过程中血清AST、ALT、HA的影响.结果:AST、ALT、HA在各组间差异均有统计学意义(P＜0.05),进一步多组间两两比较LSD't分析结果显示差异也有统计学意义(P＜0.05).结论:高剂量组的破壁灵芝孢子粉降低效果是最好的,其次是雌二醇组,最后是低剂量组.     

苦参素对肝纤维化大鼠肝脏TGF-β1的调节作用

目的观察苦参素(OM)对肝纤维化大鼠的防治作用及对转化生长因子β1(TGF-β1)表达的影响。方法采用CCl4诱导大鼠肝纤维化模型。于实验的第12周末采血,检测ALT、AST、Ⅰ型胶原和TGF-β1。肝脏病理学检测HE染色后观察肝组织改变,Masson胶原纤维染色,每组样本随机观察8个视野的肝纤维化程度,RT-PCR检测TGF-β1mRNA表达。结果苦参素组能明显降低肝纤维化大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、Ⅰ型胶原和TGF-β1水平,同时病理组织学显示苦参素能明显改善CCl4诱导的肝纤维化大鼠的肝组织结构和肝纤维化;TGF-β1基因表达量较模型组明显减少。结论苦参素可明显降低实验大鼠胶原沉积,对CCl4诱导的肝纤维化大鼠有良好的保护作用,对TGF-β1表达的影响可能是其作用机制之一。     

雷公藤红素对二乙基亚硝胺诱导的大鼠肝纤维化的治疗作用及机制

目的观察雷公藤红素(Celastrol,Cel)对二乙基亚硝胺(DEN)诱导大鼠肝纤维化的治疗作用及机制。方法采用DEN诱导大鼠肝纤维化模型,分为正常对照组、模型组、Cel给药组(2、4、8 mg.kg-1)和秋水仙碱组(Col,0.1 mg.kg-1)。紫外分光光度法检测各组大鼠血清中AST、ALT、肝组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及肝组织中丙二醛(MDA)、羟脯氨酸(HYP)的含量;ELISA检测大鼠血清中透明质酸(HA)、层粘蛋白(LN)、Ⅲ型前胶原(PCIII)、Ⅳ型前胶原(CIV)、TGF-β1的含量;Western blot检测肝脏α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(ColⅠ)和TGF-β1蛋白的表达;HE染色观察肝组织病理形态学变化;Masson染色观察肝组织中胶原沉积变化。结果与模型组比较,Cel能明显降低肝纤维化大鼠血清中升高的TGF-β1、ALT、AST、HA、LN、PCIII含量,降低肝组织中升高的HYP和MDA的含量,明显升高肝组织中SOD和GSH-Px酶活性,减少肝纤维化大鼠肝组织中α-SMA、Col I和TGF-β1的表达,改善其肝脏病理损伤程度,减少肝脏中胶原沉积。结论 Cel对肝纤维化大鼠有很好的治疗作用,其作用机制可能与Cel的抗氧化作用,降低TGF-β1的表达,抑制HSC活化,抑制胶原合成有关。     

七叶皂苷钠通过抑制4EBP1的磷酸化进而减缓CCl4诱导的大鼠肝纤维化

目的研究七叶皂苷钠(Sodium Aescinate,SA)对四氯化碳诱导的大鼠肝纤维化的抑制作用。方法41只健康♂SD大鼠随机分为正常对照组(n=5)、模型组(n=18)以及七叶皂苷钠治疗组(n=18)。在8周实验结束后取大鼠肝脏组织,HE染色观察肝脏组织的形态结构,Masson染色观察胶原纤维增生,免疫组化检测相关蛋白的表达;MTT法测定大鼠肝星状细胞HSC-T6细胞增殖,流式细胞仪检测细胞凋亡,Western blot法检测细胞蛋白的表达。结果七叶皂苷钠可以抑制四氯化碳诱导的大鼠肝纤维化形成,抑制肝星状细胞的增殖,并能促进其凋亡,且能抑制p-4EBP1、I型胶原及Ⅲ型胶原的表达。结论七叶皂苷钠通过抑制4EBP1磷酸化进而抑制肝脏纤维化的进程。     

三羟基异黄酮对肝纤维化大鼠血清和肝组织中TGF-β1表达的影响

目的观察4,5,7-三羟基异黄酮（Genistein）对四氯化碳（CCl4）诱导的肝纤维化大鼠的防治作用及对转化生长因子β1（TGF-β1）表达的影响。方法采用CCl4造成大鼠肝纤维化模型,在实验的第10周末采血和取肝组织,检测血清中ALT、AST、TGF-β1和Ⅰ型胶原,HE染色法观察肝组织改变,免疫组织化学法检测肝组织TGF-β1表达。结果血清学检测显示Genistein能明显降低肝纤维化大鼠ALT、AST、TGF-β1和Ⅰ型胶原水平,病理组织学观察发现Genistein能明显改善肝纤维化大鼠肝组织结构和肝纤维化,免疫组织化学检测表明肝组织TGF-β1表达量与模型组比较显著降低。结论 Genistein对CCl4诱导的肝纤维化大鼠有较好的保护作用,对TGF-β1表达的影响可能是其作用机制之一。     

豹皮樟总黄酮调控瘦素、TGF-β1对肝纤维化大鼠的预防作用研究

目的研究豹皮樟总黄酮(TFLC)调控瘦素(leptin)和转化生长因子-β1(TGF-β1)对肝纤维化大鼠的预防作用。方法采用CCl4诱导大鼠肝纤维化模型,TFLC灌胃给药第12周末,检测ALT、AST及HA、LN、PⅢNP、CⅣ含量;检测Ⅰ型胶原(CollagenⅠ)、瘦素、TGF-β1的含量;检测Hyp及组织病理变化;检测瘦素受体(OB-Rb)、TGFβ1Ⅰ型受体(TGFβR1)、Smad3 mRNA及蛋白表达。结果 TFLC(200、400 g.L-1)能明显降低肝纤维化大鼠肝纤维化指标及血清Ⅰ型胶原、瘦素、TGF-β1水平;降低Ob-Rb、TGFβR1、Smad3的mRNA及蛋白表达。结论 TFLC能有效预防CCl4诱导的大鼠肝纤维化,可能与下调肝内瘦素及其受体,抑制TGF-β1/Smad通路有关。     

白芍总苷对免疫性肝纤维化大鼠肝组织NF-κB和TGF-β1蛋白表达的影响

目的研究免疫性肝纤维化大鼠肝组织中核转录因子-κB(nuclear factor-κB,NF-κB)和转化生长因子β1(trans-forming growth factor beta1,TGF-β1)的变化以及白芍总苷(TGP)对两者蛋白表达的影响。方法采用猪血清诱导建立大鼠肝纤维化模型,肝组织HE染色和V-G染色观察肝组织损伤及胶原表达变化;免疫组化S-P法观察NF-κB p65和TGF-β1蛋白表达;显微摄像及图像分析检测胶原、NF-κBp65和TGF-β1蛋白的表达量。结果与正常组比较,模型组大鼠肝组织明显破坏,胶原合成增加,NF-κB p65和TGF-β1表达增强(P<0.01);与模型组比较,TGP治疗组肝组织破坏减轻,纤维化程度也明显改善,胶原面积、NF-κB p65和TGF-β1表达均明显减少(P<0.01),三者呈相关性。结论NF-κB介导TGF-β1产生或活化在免疫性肝纤维化过程中可能发挥着重要作用,而TGP抑制纤维化大鼠肝组织NF-κB和TGF-β1的表达可能是TGP的抗肝纤维化主要作用机制之一。     

川芎嗪抗实验性肝纤维化组织中TGF-β1阳性面积率表达的比较

目的:观察川芎嗪对大鼠实验性肝纤维化作用的治疗效果。方法:采用四氯化碳(CCL4)诱导大鼠肝纤维化模型,将实验动物随机分为正常对照组(N)5只、肝纤维化模型组(H)20只、川芎嗪治疗组(TM P)20只,除正常对照组以外其它两组均给予40%四氯化碳(CCL4)花生油溶液0.3m l/100g腹腔注射,每周2次,共6周。川芎嗪组于肝纤维化模型建立后给予盐酸川芎嗪(TM P)60m g/kg经口灌胃,1次/d,连续治疗60天;其余两组同时给予同等剂量的生理盐水。于60天后分别处死各组大鼠。用免疫组织化学方法染色观察肝组织中转化生长因子β1(TGF-β1)表达的变化,并利用计算机图像分析技术测量正常对照组、肝纤维化模型组及川芎嗪治疗组TGF-β1表达的平均阳性面积。结果:免疫组织化学S-P法染色显示TM P能明显抑制肝组织中TGF-β1水平的表达,TGF-β1在川芎嗪治疗组中的表达明显低于肝纤维化模型组,TGF-β1在川芎嗪治疗组与肝纤维化模型组之间有显著性差异(P<0.01);TGF-β1在川芎嗪治疗组与正常对照组中呈高表达,TGF-β1在川芎嗪治疗组与正常对照组之间差异无显著性(P>0.05)。结论:川芎嗪对四氯化碳(CCL4)诱导的大鼠实验性肝纤维化有明显的保护和治疗作用。     

血小板反应蛋白-1在大鼠肝纤维化中表达的意义

目的研究血小板反应蛋白-1(TSP-1)在肝纤维化模型大鼠肝组织中的表达,探讨TSP-1在肝纤维化发病机制中的作用。方法选择健康雄性大鼠30只,随机分为正常组10只,模型组20只,选用四氯化碳(CCL4)、饮酒、高脂低蛋白饮食等复合因素诱导肝纤维化模型,造模8周,取两组大鼠肝组织HE染色病理观察、纤维化分级,测定肝脏指数、血清透明质酸(HA)、肝组织羟脯氨酸(Hyp)含量及免疫组化法测定肝组织中TSP-1的表达量。结果复合因素大鼠肝纤维化模型造模成功,肝组织病理显示炎症明显、纤维化形成,模型组大鼠肝脏指数、血清HA肝组织Hyp及TSP-1较正常组显著升高,TSP-1在肝组织的表达量与肝纤维化程度成正比。结论TSP-1在肝纤维化发生发展过程中可能发挥了病理作用。     

The effects of repeated exposure on the reward-enhancing effects of nicotine

Nicotine increases operant responding for a weakly reinforcing audiovisual stimulus in rats, but the role of repeated exposure in the development of this effect has not been explicitly investigated. This study investigated, in two experiments, whether repeated nicotine exposure is a requisite for the expression of a reward-enhancing effect in rats, using a probe design by administering nicotine acutely at a range of doses (0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg) both before and after two weeks of daily administration of 0.3 mg/kg of nicotine. Nicotine did not enhance responding for an audiovisual stimulus relative to baseline at any dose when administered before repeated daily administration, but responding was enhanced at 0.1, 0.3, and 1.0 mg/kg of nicotine after daily administration. The results suggest that repeated exposure to nicotine is a requisite for the expression of reward-enhancing effects, and implicate sensitization to the effects of nicotine in this process.     

MHD应用于治疗尿毒症的效果及对Hcy水平的影响

目的 观察维持性血液透析(MHD)对尿毒症的治疗效果,及对同型半胱氨酸(Hcy)水平的影响.方法以2014年3月至2015年10月接受治疗的尿毒症患者为观察对象.根据其治疗方式分为腹膜透析组(n=48)和维持性血液透析组(n=52).比较2组患者透析前后血生化指标、炎性细胞因子和Hcy水平以及生活质量的差异.结果2组患者治疗前的BUN、SCr和GFR水平无明显差别,治疗后,2组患者的BUN、SCr水平较治疗前降低,GFR水平较治疗前升高,且维持性血液透析组变化更明显(P<0.05);2组患者治疗前的IL-18、IL-6、hs-CRP和Hcy水平无明显差别,治疗后,2组患者上述指标水平均较治疗前降低,且维持性血液透析组降低更明显(P<0.05);2组患者治疗前生活质量得分无明显差别,治疗后,2组患者生活质量均较治疗前增高,且维持性血液透析组增高更明显(P<0.05).结论维持性血液透析对尿毒症有较好的治疗效果,可明显改善患者血生化指标,提高患者的生活质量.     

β2受体激动剂对哮喘豚鼠糖皮质激素受体功能影响的研究

目的探索β2受体激动剂(β2AA)对哮喘豚鼠血淋巴细胞糖皮质激素受体(GR)功能的影响.方法采用放射性配基结合分析法测定哮喘豚鼠血淋巴细胞GR的Kd及Bmax,用凝胶阻滞分析法测定GR与糖皮质类固醇反应片段(GRE)的结合能力.结果各组淋巴细胞GR的Kd无明显差异(P＞0.05);沙丁胺醇组淋巴细胞GR的Bmax与对照组比较无明显差异(P＞0.05),沙丁胺醇组GR与GRE结合值[(1.5±0.4)RDU]与对照组[(8.7±2.4)RDU]比较差异有显著性(P＜0.01),地塞米松组GR与GRE组合值[(15.9±3.2)RDU]与对照组比较差异有显著性(P＜0.01),沙丁胺醇加地塞米松组(7d,14d)GR与GRE结合值[(4.9±2.1)RDU,(2.2±0.8)RDU]与对照组比较差异有显著性(P＜0.01),且遂渐下降,具有时间依赖性.结论β2AA可降低GR与GRE的结合能力,削弱糖皮质激素的作用,长期应用β2AA治疗哮喘是不恰当的.     

白藜芦醇苷降血脂作用的实验研究

目的 研究白藜芦醇苷的降血脂活性.方法 通过饲喂高脂饲料建立高脂血症大鼠和家兔动物模型,分别连续给药7d和14 d,观察白藜芦醇苷对2种动物模型血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)水平的影响.结果 白藜芦醇苷显著降低高血脂家兔血清TC、TG和LDL水平,能明显对抗大鼠升高的血清TG含量.结论 白藜芦醇苷具有降血脂的作用.     

Studies on the central effects of bulbocapnine

In the present investigation the central effects of bulbocapnine were studied. In mice and rats, the antagonism and synergism on the part of various substances on bulbocapnine catalepsy were investigated, together with the influence of the drug on the EEG in animals with chronically implanted electrodes.In mice and rats, three types of drugs proved to be effective in attenuating the bulbocapnine-induced catalepsy: antihistaminics (diphenhydramine, promethazine), antiparkinsonians (amantadine, trihexyphenidyl), and antidepressives (imipramine). Potentiation in both intensity and duration of catalepsy was noted after administration of l-DOPA and 5-HTP. In rabbits, all the components of the cataleptic syndrome were much less marked than in the other animal species. Cats proved to be the most sensitive animal, the smallest effective dose of bulbocapnine being 5 mg/kg, s.c.A biphasic effect of bulbocapnine was demonstrated in the experiments involving concomitant observations of EEG and behavior. In none of the animal species used were significant alterations of the cerebral electrical activity observed during the cataleptic state. In mice and rats, spikes appeared in the EEG only after the onset of immobility and they anticipated the excitatory phase.Some of the described effects are interpreted as the results of an influence of the alkaloid on the central catecholaminergic system.     

双黄酮类化合物药理作用研究

双黄酮类化合物广泛存在于银杏和卷柏等植物中,其抗炎和抗氧化、抗微生物以及抗肿瘤等多种作用引起关注,本文综述相关药理作用研究进展。     

龙利叶抗过敏作用的实验研究

目的探讨龙利叶的抗过敏作用。方法采用大鼠被动皮肤过敏和致敏豚鼠引喘法,观察龙利叶的抗过敏作用。结果龙利叶能明显抑制大鼠被动皮肤过敏,对豚鼠过敏性支气管痉挛及过敏性休克有对抗作用。结论龙利叶具较好的抗过敏作用。     

Adverse effects of drugs on the blood

Amongst adverse drug reactions blood dyscrasias are not frequent, but they may have serious consequences. Compared with Sweden, data from The Netherlands are scarce. It is to be expected that regular reports about the incidence of drug-induced blood dyscrasias may play an important role in general prevention.Blood dyscrasias may be caused by a variety of drugs, from many pharmacotherapeutic groups with diverse chemical structures and with all application forms. Metabolism and distribution may influence the activity of drugs.Drug-induced anaemias, including aplastic anaemia, are briefly discussed. Toxic and immune mechanisms may occur. The same holds with regard to the leucopenias. Drug-induced thrombocytopenia is mainly immunemediated (cytostatics being excluded as causative agents). In immune-mediated drug-induced blood dyscrasias often haptens must be formed. They can be formedin vivo in the liver or in the lymphocytes. In some cases they appear to be formed evenin vitro.Tracing the causative agent of a dyscrasia, be it a drug or some other substance, requires a series of investigations, comprising usage of the drug, serology and cell culture. Provocation tests are seldom justified. Distinct preventive measures can be taken to minimize the risk of blood dyscrasias: avoidance of risky drugs, awareness of the patient about early clinical signs and haematological control.     

Study on the cerebral effects of sabeluzole

The cerebral effects of subeluzole have been studied using the following methods: hypobaric hypoxia in mice, complete ischemia by decapitation in mice, anoxic hypoxia in mice, hemic hypoxia in rats, incomplete ischemia by bilateral carotid ligation in rats, anoxic hypoxia in rats and asphyxic hypoxia in cats. Sabeluzole was active in all the models used: it increased the survival time in hypobaric hypoxia (maximum at 40 mg/kg--by 92.0%, p less than 0.001), survival time in anoxic hypoxia in mice (maximum at 40 mg/kg--by 27.2%, p less than 0.001), gasping in decapitation model (maximum at 20 mg/kg--by 155.4%, p less than 0.001) and survival in hemic hypoxia (maximum at 2.5 mg/kg--by 21.1%, p less than 0.05). The duration of the effect as evaluated in the decapitation model was about 6 h. In incomplete ischemia in rats, however, it showed a weak effect. In anoxic hypoxia in rats, sabeluzole (5 mg/kg i.v.) increased the time latency between onset of anoxia and negative DC-shift by 20.5% and the K+e-threshold by 25.7%. In asphyxic hypoxia in cats, sabeluzole (0.5 mg/kg i.v.) counteracted the hypoxia-induced decrease of the fast-wave amplitudes during the cortical resistance period and the hypoxia-induced decrease of the slow-wave and increase of the fast wave amplitudes during the cortical recovery period.