芹菜素对大鼠非酒精性脂肪性肝炎肝组织过氧化物酶体增殖物激活受体表达的影响

目的 探讨芹菜素对非酒精性脂肪性肝炎(NASH)大鼠肝组织过氧化物酶体增殖物激活受体(PPARs)表达的影响. 方法 采用高脂饲料喂养的方法复制大鼠NASH模型,成模后分为正常组,模型组,多烯磷脂酰胆碱组,芹菜素低剂量组、中剂量组和高剂量组.实验结束后,进行胰岛素敏感性测定;腹腔静脉取血测定生物化学指标ALT、AST、总胆固醇(TC)、总甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FBG)和空腹胰岛素(FINS);计算肝指数和胰岛素抵抗指数(HOMA-IR);提取肝组织,运用免疫组织化学和RT-PCR测定各组大鼠肝组织PPAR α 、PPAR γ蛋白和mRNA表达情况.多组间的比较采用单因素方差分析.结果 胰岛素敏感性的变化:各组之间差异均有统计学意义,两两比较结果显示,正常组明显高于其他组,而芹菜素组高于模型组,尤其是高剂量组;生物化学指标检测结果显示:与模型组ALT[(163.1±15.5) U/L、AST (284.6±23.5) U/L]活性和TC[(2.23±0.76)mmol/L]、TG[(1.94±0.33) mmol/L]、LDL-C[(2.63±0.18) mmol/L]、HDL-C[(0.77±0.51)mmol/L]、FBG[(8.64±1.02) mmol/L]和FINS[(3.48±1.41) U/L]含量相比,芹菜素组尤其是高剂量组能减少ALT [(95.4±7.3)U/L]、AST [(183.7±14.3)U/L]活性和TC [(1.61±0.25)mmol/L]、TG[(1.23土0.21) mmol/L、LDL-C[(1.86±0.13) mmol/L、FBG[(5.29±1.45)mmol/L和FINS[(0.76±0.86) U/L]的含量,升高HDL-C[(1.04±0.17) mmol/L]的含量;与模型组大鼠肝指数(3.75±0.25)和HOMA-IR (1.34±0.06)相比,芹菜素组尤其是高剂量组能够显著减低肝指数(2.90±0.17)和HOMA-IR(0.18土0.04,P＜0.05);免疫组织化学染色和RT-PCR结果显示:与模型组相比,芹菜素组PPAR α 、PPARγ蛋白和mRNA表达增加,尤其是高剂量组,PPAR α 蛋白和mRNA相对表达量分别为18.27±4.05和0.63±0.02,PPAR γ蛋白和mRNA相对表达量分别为8.48±5.05和0.39±0.02,P＜0.05. 结论 芹菜素能改善胰岛素抵抗和糖脂代谢,减轻肝脏脂肪变性和炎症坏死,降低血清TC、TG、LDL-C、FBG、FINS和HOMA-IR水平,提高HDL-C水平,推测其可能对大鼠NASH具有保护作用.     

复方茵陈蒿汤颗粒剂治疗慢性乙型肝炎110例(摘要)

目的:探讨复方茵陈蒿汤颗粒剂对慢性乙型肝炎的治疗作用。方法:治疗组110例,用复方茵陈蒿汤颗粒剂(药物组成:茵陈、垂盆草、平地木、六月雪各30g,焦山栀、制大黄、丹皮各10g),每日1帖量,分3次服用,4周为1个疗程,共治疗     

柴胡皂苷D对非酒精性脂肪性肝炎大鼠糖脂代谢紊乱的影响

目的:观察柴胡皂苷D对非酒精性脂肪性肝炎(NASH)大鼠糖脂代谢紊乱和肝脏脂肪变性的影响。方法:44只雄性Wistar大鼠随机分为普通饲料喂养的空白组(C,n=10)和高脂高糖饲料喂养造模组(n=34),造模8周后造模组大鼠随机分为模型组(M)、西药组(R)、柴胡皂苷D组(CD),分别给予生理盐水、罗格列酮、柴胡皂苷D灌胃治疗4周,同时继续高脂高糖饲料喂养。12周后检测大鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C),血清丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)、血清总胆汁酸(TBA)和游离脂肪酸(FFA),以及空腹血糖(FBG)、胰岛素(FINS)水平并计算胰岛素抵抗指数(IRI)。肝组织病理切片HE染色,光镜下观察脂肪变性和炎症程度。结果:CD组大鼠体重、肝湿重、TC、TG、FBG、FINS、IRI、FFA、TBA、ALT水平较M组显著降低(P0.05或P0.01),HDL-C、LDL-C水平未见显著变化(P0. 05)。结论:柴胡皂苷D能够显著改善NASH大鼠胰岛素抵抗和糖脂代谢紊乱,减轻肝脏脂肪变程度。     

复方甘枣宁预防大鼠非酒精性脂肪肝的实验研究

[目的]研究复方甘枣宁对高脂饮食诱发的大鼠脂肪肝的预防作用.[方法]采用高脂饲料喂饲制作大鼠非酒精性脂肪肝模型,同时以复方甘枣宁灌胃,12周后检测血清中总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)水平,并作病理组织学观察,同时称体重、肝脏重,计算肝指数.[结果]复方甘枣宁明显减轻肝组织内脂肪变性,降低血清TC与AST水平.[结论]复方甘枣宁对高脂饮食诱发的大鼠非酒精性脂肪肝具有一定的预防作用.     

茵陈紫金汤对小鼠四氯化碳急性肝损伤的保护作用

[目的]观察茵陈紫金汤对四氯化碳(CCl4)诱导的小鼠急性肝损伤保护作用.[方法]以0.12?l4花生油溶液经腹腔注射,制备小鼠急性化学性肝损伤模型,测定给药后模型小鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST),肝组织匀浆超氧化物歧化酶(SOD)活性以及丙二醛(MDA)水平,计算肝脏指数,光镜下观察肝组织病理学变化.[结果]茵陈紫金汤高、中剂量组均能显著降低CCl4所致小鼠急性肝损伤血清ALT、AST活性,提高肝组织匀浆SOD活性,降低MDA及肝脏指数,明显改善肝组织损伤的程度,与模型组比较差异有统计学意义(P＜0.05).[结论]茵陈紫金汤对CCl4诱导的小鼠急性肝损伤有保护作用,其作用机制可能与抗脂质过氧化有关.     

苓桂术甘汤对NASH大鼠肝组织DGAT2、PKCε的作用研究

[目的]探讨苓桂术甘汤对非酒精性脂肪性肝炎(NASH)大鼠肝组织DGAT2、PKCε的影响。[方法]高脂饮食饲养SD大鼠8周制备NASH模型,药物治疗4周后,自动生化分析仪检测血清肝功能(AST、ALT)、血脂(CHO、LDL、HDL、TG)水平,苏木精-伊红染色、油红O染色观察肝组织病理,RT-PCR检测DGAT2mRNA、PKCεmRNA,Western-blot检测DGAT2和PKCε蛋白的表达。[结果]苓桂术甘汤组、罗格列酮组能明显改善肝组织的脂肪变性和炎症程度,降低血清TG、ALT、AST,下调DGAT2、PKCεmRNA和蛋白的表达水平(P0.05、P0.01)。[结论]苓桂术甘汤可能是通过下调肝组织DGAT2、PKCεmRNA和蛋白的表达水平,对肝内脂质代谢和胰岛素抵抗起到了调节和改善作用,从而达到治疗NASH的目的,DGAT2/PKCε有可能成为治疗NASH的新靶点。     

鲜葛花汁对大鼠急性酒精性肝损伤的保护作用

[目的]观察鲜葛花汁对大鼠急性酒精性肝损伤的预防保护作用.[方法]以单味葛花汤、益肝灵为对照,各组大鼠均先给予相应的药物灌胃,0.5 h后以白酒灌胃造成急性酒精性肝损伤模型,每天2次,连续灌胃7 d,第7天处死全部大鼠,检测血清和肝组织丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST),同时光镜观察肝组织病理形态学的改变.[结果]鲜葛花汁能有效降低急性酒精性肝损伤模型大鼠血清及肝组织ALT、AST的升高,且作用显著优于对照组(P＜0.01);同时对大鼠肝组织病理形态学改变具有明显改善作用.[结论]鲜葛花汁可用于治疗酒精及其他原因引起的肝损伤.     

糖肝煎对糖尿病性脂肪肝模型大鼠糖脂代谢及转胺酶的影响

目的观察糖肝煎(TGJ)对2型糖尿病并脂肪肝实验性大鼠糖脂代谢相关指标及转胺酶的影响。方法小剂量链脲佐菌素(strep-tozocin STZ)注射加高脂饲料喂养,建立2型糖尿病并脂肪肝实验性大鼠模型,分别给予糖肝煎(分为大剂量糖肝煎组、中剂量糖肝煎组、小剂量糖肝煎组),文迪雅(马来酸罗格列酮片GlaxoSmithk line公司文迪雅组)和生理盐水(模型组)与正常大鼠(正常组)对照,测空腹血糖(FPG)、负荷后血糖(P2hPG)空腹胰岛素(FINS)、负荷后胰岛素(P2hINS)甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-c)、游离脂肪酸(FFA)、脂蛋白脂酶(LPL)、谷丙转氨酶(AST)、谷草转氨酶(ALT)、总胆红素(Tbil)并以稳态模型法计算胰岛素抵抗指数(HOMA-IR)。结果糖肝煎与模型组比较,中剂量组改善P2hPG、P2hINS、FINS、HOMA-IRTG、LDL-C、FFA、HDL-C、AST、ALT等指标有显著性差异(P<0.05),与文迪雅组比较,降低AST、ALT有显著性差异(P<0.05)。结论糖肝煎中剂量能有效改善2型糖尿病并脂肪肝模型实验性大鼠胰岛素抵抗状态,并能降糖调脂,降低转氨酶,保护肝脏。     

关于茵栀黄、苦黄注射液等中药制剂在肝病临床的合理运用

中药制剂茵栀黄、苦黄注射液在肝病临床中的运用历来已久,其主要功效是护肝、退黄,适应症为急慢性黄疸型肝炎(湿热型)。在用药前,首先要对疾病辨证分型。掌握该药的适应症,才能取得满意的疗效。 茵栀黄注射液是茵陈、栀子、黄芩、金银花等中药的提取物;苦黄注射液是苦参、大黄、大青叶、茵陈等药的提取物。上述药物大都属苦寒之剂,功效为清热、泻火、解毒、     

降脂益肝冲剂对NASH大鼠肝脏抵抗素mRNA表达的影响

目的:观察降脂益肝冲剂对非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)大鼠肝脏抵抗素mRNA表达的影响,并探讨抵抗素在大鼠NASH发病机制中的作用.方法:24只♂Wistar大鼠随机分为3组:正常组普通饲料喂养,模型组和治疗组高脂饮食喂养.治疗组在高脂饮食12 wk后给予降脂益肝冲剂,同时模型组和正常组给予等量的生活饮用水灌胃,17 wk末处死各组大鼠.观察动物一般情况,肝组织脂肪变性及炎症活动程度,测定血清TNF-α、ALT、AST,空腹血糖(FBG)、空腹胰岛素(FINS),并计算胰岛素敏感指数(ISI);RT-PCR法检测肝组织抵抗素mRNA相对含量.结果:在正常肝脏组织探测到抵抗素mRNA的微量表达(0.42±0.08),模型组其表达量显著升高(2.14±0.11,P<0.01),与模型组相比治疗组则显著下降(0.90±0.06,P<0.01).模型组抵抗素水平与血清TNF-α、ALT、AST水平、肝脏炎症活动度计分成显著正相关(r=0.873,0.772,0.716,0.892,P<0.05),与ISI无相关.治疗组上述各项指标均得到显著改善.结论:抵抗素与反映肝脏炎症程度及肝功能的指标密切相关,可能在NASH的发病中起重要作用.降脂益肝冲剂对NASH有很好的疗效,抵抗素是其可能的作用靶点.     

Fine structure of rat islet cell tumors induced by streptozotocin and nicotinamide

Summary Young male Holtzman rats were injected intravenously with 50 mg/kg of Streptozotocin, preceded and followed by a single intraperitoneal injection of 350 mg/kg of nicotinamide, according to the method of Rakieten et al. [16]. After 245 to 323 days, 27 pancreatic islet cell tumors measuring up to 0.6 cm were demonstrable in 20 of 41 rats so treated; they were solitary in 15 and multiple (two or three neoplasms each) in five animals. It was not possible to distinguish between tumor-bearing and tumor-free rats on the basis of periodic blood sugar determinations and serum insulin assays. Mean insulin concentration in grossly tumor-free pancreatic specimens was 0.661 units of insulin/g of wet tissue, but amounted to 5.385 units/g in specimens containing tumor. The islet cell tumors were rounded and well delineated. They were located in all parts of the pancreas. In general, their cells stained deeply with aldehyde-fuchsin. Ultra-structurally, most tumors consisted of well granulated B cells. A or D cells were not encountered while occasional EC cells were identified. Nucleoli were frequently prominent. Some necrotic B cells and others with few or unusually small secretory granules were present. Extravasated erythrocytes as well as hemosiderin deposits were seen in many tumors, and tumor cell particles were occasionally noted within the lumina of capillaries. Distant metastases were not demonstrable in this group of animals.Supported by a grant from the National Institutes of health, No. A.2203Presented at the Eighth Congress of the International Diabetes Federation, Brussels, Belgium, June, 1973     

LL-37抗菌肽重组及其治疗实验性内毒素血症的研究

目的重组抗菌肽LL-37并探讨其治疗内毒素血症的疗效。方法提取人肺腺上皮SPC-A-1细胞总RNA,RT-PCR扩增出LL-37肽cDNA,构建pGEX-1λT-LL-37重组质粒并转染大肠杆菌JM109,培养转染细菌并诱导表达融合蛋白,裂解细菌,亲和层析出融合蛋白,裂解融合蛋白生成LL-37肽,高压液相色谱法提纯LL-37;建立BALB／C小鼠内毒素血症模型并观察LL-37的疗效。结果重组肽核苷序列5’-端比天然序列多4个密码子,N-端多4个氨基酸残基。小、大剂量LL-37治疗组（Ⅰ组、Ⅱ组）及内毒素血症组（Ⅲ组）6h存活率分别为62．5％、87．5％、0;Ⅰ、Ⅱ组平均存活时间和最长存活时间均长于Ⅲ组;Ⅰ、Ⅱ组24h后小鼠存活率有差异,量效关系明显。结论重组抗菌肽LL-37可用于内毒素血症的治疗。     

Experimental and Natural Infections of Tick-Borne Encephalitis Virus in Dogs

Dogs are frequently infected with the tick-borne encephalitis virus (TBEV). However, to date, only a few clinically manifest cases of tick-borne encephalitis (TBE) have been reported in dogs. In this study, three-month-old beagle dogs were infected with TBEV through a subcutaneous injection. Body temperature, clinical signs, blood haematology, blood biochemistry, and immune responses were monitored for up to 28 days postinfection (p.i.). No changes in body temperature or clinical signs were observed in the infected dogs. Most haematology and blood biochemistry parameters were unchanged after the infection, except for a slight reduction in blood lymphocyte counts, but they were within the physiological range. Low-titre viraemia was detected in 2/4 infected dogs between days 1 and 3 p.i. All infected dogs developed a robust immune response, in terms of neutralising antibodies. Thus, TBEV infections lead to effective seroconversion in dogs. Next, to assess TBEV exposure in dogs in the TBEV-endemic region of the Czech Republic, we conducted a serosurvey. Virus neutralisation tests revealed TBEV-specific antibodies in 17 of 130 (13.07%) healthy dogs, which confirmed a high, but clinically inappreciable TBEV exposure rate in the endemic area. The seropositivity rate was similar (12.7%; 41 positives out of 323) in a subgroup of dogs with various clinical disorders, and it was 13.4% (23 out of 171) in a subgroup of dogs with signs of acute neurological disease. Two dogs with fatal acute meningoencephalitis showed positive results for TBEV-specific IgM and IgG antibodies. These data extended our understanding of the clinical presentation of TBEV infections.     

Development and Verification Experiment of In-Situ Friction Experiment Device for Simulating UV Irradiation in Space

In order to explore the influence of space ultraviolet radiation on spacecraft lubricating materials, an in-situ friction experimental device simulating space ultraviolet radiation was developed in the laboratory, and the experimental verification was carried out. This paper firstly introduced the design index, structure and working principle of the space ultraviolet irradiation simulation device, and then calibrated and tested the parameters of the whole device, and also conducted a virtual operation of the device’s operation effect by simulation software, and the results showed that it met the design index. Finally, the validation tested of the ultraviolet irradiated in-situ friction experimental device were described in detail. By using the device to irradiate the samples, it was found that the in-situ ultraviolet irradiation device could achieve the expected irradiation effect, and the irradiation would lead to changes in the surface structure and properties of the PTFE material, while also achieving the need for in-situ spatial friction property testing of the material, providing favorable conditions for future testing.     

Erythropoietin Formation in Rats with Experimental Hypersplenism

Splenomegaly accompanied by anaemia, increased reticulocyte and decreased thrombocyte counts, was induced in Wistar rats by a long-term intraperitoneal administration of methylcellulose. Compared to controls, hypersplenic rats showed significantly enhanced utilization of ⁵⁹Fe by red cells and increased titre of erythropoietin. After the exposure of rats to hypoxic hypoxia corresponding to an altitude of 7,000 m for 6 h, no difference in the erythropoietin titre was found in either group. The results suggest that experimental hypersplenism alone does not affect the production of erythropoietin and does not stimulate the formation of an inhibitor of erythropoietin or erythropoiesis. The increased titre of erythropoietin and enhanced utilization of radioiron by red cells in rats with hypersplenism were found to be due to haemolytic anaemia leading to the stimulation of erythropoiesis.     

Optimizing the temporal dynamics of light to human perception

No previous research has tuned the temporal characteristics of light-emitting devices to enhance brightness perception in human vision, despite the potential for significant power savings. The role of stimulus duration on perceived contrast is unclear, due to contradiction between the models proposed by Bloch and by Broca and Sulzer over 100 years ago. We propose that the discrepancy is accounted for by the observer’s “inherent expertise bias,” a type of experimental bias in which the observer’s life-long experience with interpreting the sensory world overcomes perceptual ambiguities and biases experimental outcomes. By controlling for this and all other known biases, we show that perceived contrast peaks at durations of 50–100 ms, and we conclude that the Broca–Sulzer effect best describes human temporal vision. We also show that the plateau in perceived brightness with stimulus duration, described by Bloch’s law, is a previously uncharacterized type of temporal brightness constancy that, like classical constancy effects, serves to enhance object recognition across varied lighting conditions in natural vision—although this is a constancy effect that normalizes perception across temporal modulation conditions. A practical outcome of this study is that tuning light-emitting devices to match the temporal dynamics of the human visual system’s temporal response function will result in significant power savings.     

Endotracheal versus intravenous epinephrine during electromechanical dissociation with CPR in dogs

The dose-response curves of epinephrine given either IV or endotracheally (ET) were compared during resuscitation from electromechanical dissociation (EMD). Ten anesthetized dogs were subjected to a two-minute period of electrically induced ventricular fibrillation (VF) followed by defibrillation without CPR to produce EMD. Mechanical CPR was followed by injection of either ET or IV epinephrine. Successful response was defined as a return of pulsatile blood pressure within two minutes of drug administration. Using log-dose increments of epinephrine, experimental trials were repeated in each animal. The IV and ET median effective doses were 14 and 130 micrograms/kg, respectively. When the trials were successful, the time between drug administration and either arterial blood pressure increases or return of spontaneous circulation did not differ significantly for the ET and IV groups. These results show that the dosage for epinephrine delivered ET must be higher than the IV dosage to achieve the same response during CPR.     

实验性慢性氟中毒兔病理演变过程及其机理探讨

80只纯系大耳白幼兔随机分为三组,一组做对照,其余两组分别用10mg/Kg/日和20mg/Kg/日氟化钠喂养。各组动物分别在实验饲养30、90、150、210和250天时以气栓处死进行检查。结果表明:血清F~-的浓度与供氟的量及摄氟时间成正比,血清Ca、P和ALP的水平在不同实验期加氟各组与对照组之间无区别意义(P>0.05)。实验90天后加氟各组动物发生氟斑牙和X线诊断的氟骨症。病理学观察表明,氟中毒动物不仅能引起关节软骨的营养不良性退变,也引起软骨成骨和膜内成骨两个过程的障碍,导致骨质疏松,形态学改变与甲状旁腺机能亢进所引起的纤维性囊性骨炎的形态学表现很相似。慢性氟中毒后,肝脏发生肝细胞颗粒变性和脂肪变性,肾脏发生肾小管颗粒变性、坏死、病理性钙化和肾小球萎缩。     

实验性动脉粥样硬化动物模型研究概况

动脉粥样硬化(AS)是严重危害人类健康的常见心血管系统疾病。建立实验性AS模型在该病的发生机制、病理变化及药物疗效等实验研究中起着重要作用。本文分别以鹌鹑、豚鼠、小鼠、大鼠、家兔、小型猪为载体,对以不同方法建立的AS动物模型进行整理归纳,比较分析了各种动物模型的特点,为今后更好的建立AS动物模型提供参考。     

JSH-23 targets nuclear factor-kappa B and reverses various deficits in experimental diabetic neuropathy: effect on neuroinflammation and antioxidant defence

Aim: Nuclear factor‐kappa B (NF‐κB) being reported to play an important role in the pathogenesis of diabetic neuropathy is believed to be a central mechanism involved in the genesis and promulgation of inflammatory insult. Here we have targeted the nuclear translocation of NF‐κB using JSH‐23 to elucidate its role in diabetic neuropathy. Methods: JSH‐23 (1 and 3 mg/kg) was administered for 2 weeks in diabetic rats, after 6 weeks of diabetes induction using streptozotocin (55 mg/kg) as diabetogenic agent. Functional (motor nerve conduction velocity and blood flow), behavioural (mechanical hyperalgesia), biochemical [malondialdehyde, glutathione, tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) levels] and NF‐κB translocation studies (western blot technique) were then undertaken. Results: JSH‐23 treatment significantly reversed the nerve conduction and nerve blood flow deficits seen in diabetic animals. Reduction in mechanical pain threshold was also partially corrected by the treatment. Protein expression studies showed that nuclear translocation of p65/p50 subunit was inhibited by JSH‐23 treatment in the sciatic nerve. The treatment also lowered the elevated IL‐6, TNF‐α, cyclo‐oxygenase (COX‐2) and inducible nitric oxide synthase (iNOS) levels/expression, indicating reduction in the inflammatory damage of the sciatic nerve. Apart from these effects, JSH‐23 also increased Nrf2 and hemeoxygenase‐1 (HO‐1) levels which could imply its potential in increasing the strength of antioxidant defence. Conclusion: We observed that NF‐κB inhibition partially reversed functional, behavioural and biochemical deficits with JSH‐23 treatment. This study substantiates the role of NF‐κB activation in the aetiology of diabetic neuropathy and protection afforded by inhibition of NF‐κB by JSH‐23, which can be attributed to its effect on neuroinflammation and oxidative stress.