白术、附子、肉桂合剂对老龄大鼠心肌Na+,K+-ATPase和血清TAA的影响

目的探讨白术、附子、肉桂合剂对老年大鼠心肌细胞膜钠钾ATP酶(Na+,K+-ATPase)活性和总抗氧化能力(TAA)的影响,及产生显著影响的时间.方法给老年Wistar大鼠灌服白术、附子、肉桂合剂水煎剂,制备血清、心肌匀浆和心肌细胞膜,分别测定血清TAA和Na+,K+-ATPase活性,并与对照组进行比较.结果老年大鼠心肌Na+,K+-ATPase活性和TAA明显低于青年对照组(P＜0.05,P＜0.01).灌服合剂后30天心肌Na+,K+-ATPase明显高于老年对照组,分别为(0.91±0.05)、(0.62±0.09)μmolPi·mg-1Pr·h-1;而血清TAA在20天时明显高于老年对照组,分别为(8.45±1.78)、(5.38±0.58)U·     

牛磺酸对2型糖尿病大鼠胰腺线粒体氧化应激的影响

目的探讨牛磺酸对糖尿病大鼠胰腺线粒体氧化应激的影响。方法将30只Wistar大鼠随机分为正常对照组、糖尿病组(DM组)和牛磺酸治疗组(Tau组,采用20g.L-1牛磺酸生理盐水溶液治疗,200mg·kg-1),前两组注射等体积的生理盐水溶液。8wk后,测3组大鼠血浆葡萄糖、胰岛素、丙二醛(MDA),胰腺线粒体MDA、Ca2+、超氧化物歧化酶(SOD)及Na+,K+-ATP酶(Na+,K+-ATPase)和Ca2+,Mg2+-ATP酶(Ca2+,Mg2+-ATPase)的活性。结果①DM组大鼠血糖、MDA和胰腺线粒体MDA、Ca2+含量明显高于对照组(P<0.01),而血浆胰岛素水平、SOD、Na+,K+-AT-Pase和Ca2+,Mg2+-ATPase活性明显降低(P<0.05)。②Tau组大鼠血糖、MDA及胰腺线粒体Ca2+、MDA含量较DM组明显降低(P<0.05),血浆胰岛素水平、SOD、Na+,K+-ATPase和Ca2+,Mg2+-ATPase活性明显升高(P<0.05)。结论牛磺酸可减轻2型糖尿病大鼠胰腺线粒体氧化应激水平。     

白术水煎剂对老龄大鼠心肌Na~+,K~+-ATPase和血清TAA的影响

目的：探讨白术对老年大鼠心肌细胞膜钠钾ＡＴＰ酶（Ｎａ＋,Ｋ＋－ＡＴＰａｓｅ）活性和总抗氧化能力（ＴＡＡ）的影响,及产生显著影响的时间．方法：给老年Ｗｉｓｔａｒ大鼠灌服白术水煎制,制备血清、心肌匀浆和心肌细胞膜,分别测定血清ＴＡＡ和Ｎａ＋, Ｋ＋－ＡＴＰａｓｅ活性,并与对照组进行比较．结果：老年大鼠心肌 Ｎａ＋, Ｋ＋－ＡＴＰａｓｅ活性和ＴＡＡ明显低于青年对照组（Ｐ＜０．０５, Ｐ＜０．０１）．灌服白术后３０天心肌Ｎａ＋, Ｋ＋－ＡＴＰａｓｅ明显高于老年时照组,分别为（０． ９１± ０． ０５）、（０． ６２ ± ０． ０９）μ　ｍｏｌＰｉ．ｍｇ－１Ｐｒ．ｈ－１;而血清ＴＡＡ在２０天时明显高于老年对照组,分别为（６．６６±０．９０）、（５．３８±０．５８）Ｕ．ｍｌ－１;两组各项比较差异均有显著性（Ｐ＜０．０１）;血清ＴＡＡ和Ｎａ＋,Ｋ＋－ＡＴＰａｓｅ呈显著的正相关。结论：白术能明显增强心肌Ｎａ＋,Ｋ＋－ＡＴＰａｓｅ活性,其机理可能与血清ＴＡＡ的提高有关,白术的显效时间为 ３０天．     

大鼠缺血性全脑损伤Na~+,K~+-ATP酶活性及其α亚基表达的变化

目的研究大鼠全脑缺血后,脑组织Na+,K+-ATPase活性及其α亚基的变化。方法采用大鼠双侧颈总动脉结扎全脑缺血模型,测定缺血后脑组织H2O,Na+和K+含量及Na+,K+-ATPase的活性,采用免疫组织化学的方法观察Na+,K+-ATPaseα亚基的改变。结果全脑缺血后,脑组织的H2O和Na+的含量明显增加,K+含量及Na+,K+-AT-Pase活性明显降低,正常大鼠海马和皮层神经元上主要分布α1和α3亚基,而α2表达较少,脑缺血后,α1和α3亚基的表达明显减少。结论Na+,K+-ATPaseα1和α3亚基参与了缺血性脑损伤。     

白术、附子、肉桂合剂对老年小鼠脑线粒体MnSOD、MDA影响的实验研究

目的：研究白术、附子、肉桂合剂对老年小鼠脑线拉体MnSOD、MDA的影响。方法：用差数离心法分离防线粒体．并检测防线粒体MnSOD(锰超氧化物歧化酶)活性及MDA(丙二醛)含量。以白术、附子、肉桂合剂水煎剂灌胃老年小鼠30d．观察其对老年小鼠上述指标的影响。结果：老年小鼠MnSOD活性降低，MDA含量升高．与老年组比较、合剂组脑线粒体MnSOD活性升高，MDA含量降低。结论：白术、附子、肉桂合剂对老年小鼠脑组织具有抗氧化作用。     

参附注射液对病毒性心肌炎模型小鼠心肌腺苷酸酶活性和钠/钙代谢的影响

目的:研究参附注射液对病毒性心肌炎模型小鼠心肌腺苷酸酶活性及钠、钙代谢的影响。方法:实验分为4组,即对照、感染及参附注射液高、低剂量组。在不同时相点分别测定小鼠心肌腺苷酸酶活性和钠/钙含量,观察组织病理变化。结果:与对照组比较,感染组心肌Na+,K+-ATPase及Ca2+-ATPase活性显著减弱,钠、钙含量显著升高(P<0.01),并早于心肌结构变化;与感染组比较,参附注射液高剂量组Na+,K+-ATPase及Ca2+-ATPase活性显著增强,钠、钙含量显著降低(P<0.01或P<0.05),且心肌炎症、坏死程度也显著减轻(P<0.01或P<0.05)。结论:参附注射液能显著改善模型小鼠病毒感染后心肌继发性损伤状况,其机制可能与抑制心肌腺苷酸酶活性下降,阻止反常性钠、钙超载有关。     

葛根素对糖尿病大鼠胰腺线粒体氧化应激及ATP酶的影响

目的探讨葛根素对糖尿病大鼠胰腺线粒体氧化应激及ATP酶的影响。方法将30只Wistar大鼠分为正常对照组、糖尿病组(DM组)和糖尿病治疗组(Pue组,采用葛根素注射液治疗),前两组注射等体积的0.9%氯化钠溶液。8周后,测3组大鼠血清葡萄糖、胰岛素、胰腺线粒体丙二醛(MDA)水平及超氧化物歧化酶(SOD)、Na+-K+-ATP酶(Na+-K+-ATPase)和Ca2+-ATP酶(Ca2+-ATPase)的活性。结果 (1)DM组大鼠血糖和MDA含量明显高于对照组(P<0.001),而血清胰岛素水平、SOD、Na+-K+-ATPase和Ca2+-ATPase活性显著降低(P<0.05)。(2)Pue组大鼠血糖及MDA含量较DM组显著降低(P<0.05),血清胰岛素水平、SOD、Na+-K+-ATPase和Ca2+-ATPase活性显著升高(P<0.05),差别有统计学意义。结论葛根素可减轻糖尿病大鼠胰腺线粒体氧化应激水平。     

心肌Na^＋，K^＋-ATP酶在抑郁症时的活性及mRNA表达

目的 探讨Na+,K+-ATP酶在抑郁症发病中的作用及其和单胺类神经递质之间的关系.方法 对SD大鼠进行慢性随机刺激建立抑郁症模型,检测大鼠心肌Na+,K+-ATP酶的活性及mRNA表达,海马组织及血液中去甲肾上腺素(NA)和5-羟色胺代谢物5-羟吲哚乙酸(5-HIAA)水平.结果 抑郁症大鼠心肌Na+,K+-ATP酶的转录水平下调(P＜0.01);酶的活性明显降低(P＜0.01);海马及血浆中的NA及5-HIAA水平显著下降(P＜0.01).结论 推测抑郁症时神经体液因素的变化可能是引起心肌细胞Na+,K+-ATP酶分子变化的原因之一,该酶在抑郁症的发病机制中有一定的生理和病理意义.     

菊苣多糖对链尿菌素糖尿病大鼠心肌缺血再灌注损伤的保护作用

目的：证实菊苣多糖对糖尿病大鼠心肌缺血再灌注的保护作用,探讨其可能的作用机制。方法：应用链尿菌素腹腔注射制作大鼠糖尿病模型,检测每天灌胃给予菊苣多糖（5g/Kg）第10周大鼠的血糖变化,第12周结扎冠状动脉左室降支60min松开结扎线再灌注60min后血清CK、LDH含量及心肌组织Na＋/K＋-ATPase活性。结果：给药10周后糖尿病对照组空腹血糖明显高于正常（空白）对照组,菊苣多糖组空腹血糖明显低于糖尿病对照组。给药12周心肌缺血再灌注后糖尿病对照组血清CK、LDH含量明显高于正常对照组及心肌组织Na＋/K＋-ATPase活性明显低于正常对照组,菊苣多糖组血清CK、LDH含量明显低于正常对照组及心肌组织Na＋/K＋-ATPase活性明显高于糖尿病对照组。结论：菊苣多糖具有明显的抗糖尿病作用,对糖尿病大鼠心肌缺血再灌注具有一定的保护作用,其机制与提高心肌组织Na＋/K＋-ATPase活性密切相关。     

异氟醚对离体大鼠心肌缺血/再灌注损伤的影响

目的研究麻醉药异氟醚对缺血/再灌注心肌功能和代谢、氧自由基及ATP酶活性的影响。方法SD大鼠56只,随机分为7小组,每组8只。采用Langendorff离体大鼠心脏模型。按给药方式又分为两大组,各组记录平衡后,给药后(或续灌15min)复灌末左室收缩压(LVSP)、左室舒张末期压(LVEDP)、左室发展压(LVDP)、左室压力升高或降低最大速率(±dp/dtmax)、心率(HR)、冠脉流量(CF)。实验结束后测定心肌超氧化物歧化酶(SOD)活性、心肌丙二醛(MDA)含量、高能磷酸盐(ATP)含量、Na+,K+-ATP酶、Ca2+-ATP酶活性。结果异氟醚组明显降低LVDP、+dp/dt,升高LVEDP(P<0.05);缺血/再灌注后,异氟醚组的LVDP分别恢复到基础值的57%、61%、59%、77%,+dp/dt分别恢复到基础值的45%、50%、46%、52%;与再灌末对照组相比,差异具有显著性;异氟醚组能提高心肌ATP含量,缺血后心肌ATP下降较慢,复灌后恢复较快;复灌后异氟醚组SOD活性较高,MDA生成量下降(P<0.05);异氟醚能提高再灌后心肌Na+,K+-ATP酶活性(P<0.05)。结论异氟醚对心肌收缩功能和Ca2+-ATP酶活性具有一定的抑制作用,能明显促进心肌功能与代谢的恢复,提高冠脉流量、心肌Ca2+-ATP酶及Na+,K+-ATP酶活性。     

Involvement of tropomyosin in the sensitivity of Na+ + K+ ATPase to ouabain

The Na⁺/K⁺ ATPase sensitivity to ouabain was shown to be increased by 300 to 1000-fold after treatment of the plasma membrane by EDTA. Addition of proteins detached from the plasma membrane with Ca²⁺ ions to EDTA treated membranes reconstituted the original Na⁺/K⁺ ATPase resistance to ouabain inhibition. Tropomyosin with Ca²⁺ ions (not with Mg²⁺ ions) induced the same effect. When suboptimal doses of tropomyosin were used for such a reconstitution, the dose-response curve indicated a full reconstitution of a given percentage of enzyme molecules. This observation led us to assume a direct or indirect effect of tropomyosin on Na⁺/K⁺ ATPase functions.     

羟基喜树碱联合氟尿嘧啶、醛氢叶酸治疗晚期结、直肠癌

目的观察羟基喜树碱（HCPT）、氟尿嘧啶（5-FU）、醛氢叶酸（CF）联合治疗晚期结、直肠癌的临床疗效。方法将80例结、直肠癌患者随机分为2组，分别采用HCPT＋5-FU＋CF方案及草酸铂（OXA）＋5-FU＋CF方案化疗2周期以上，评价疗效及毒性。结果HCPT＋5-FU＋CF组有效率50.0％，与OXA＋5-FU＋CF组（52．5％）疗效相当（P〉0．05）。毒、副作用主要为骨髓抑制、胃肠道反应及脱发。结论HCPT＋5-FU＋CF方案治疗晚期结、直肠癌疗效高，毒、副作用轻微。     

Abacavir + dolutegravir + lamivudine for the treatment of HIV

Introduction: Since the last revision of both European and American guidelines (EACS and DHHS), new data from clinical trials and cohort studies, as well as experience in clinical practice, have prompted significant changes to the list of recommended/preferred options for the treatment of HIV infected patients, highlighted the role of INSTI-based regimens. Dolutegravir (DTG) in combination with abacavir/lamivudine (ABC/3TC) is one of these preferred regimens in multiple clinical scenarios, including treatment-naive and treatment-experienced patients.

Areas covered: In this article we describe the coformulation of ABC/3TC/DTG in a fixed-dose combination (FDC) approved in September 2014 for the treatment of HIV infection. We focused our research on the efficacy and safety data resulting from phase 2 and 3 clinical study, particularly on the results of both SPRING (1 and 2) and SINGLE studies.

Expert opinion: Triple combination therapy with ABC/3TC/DTG should be considered among the initial options for treatment-naive patients, being effective, well tolerated, with a high genetic barrier to resistance along with a convenient once-daily administration.

In treatment-experienced patients the single-tablet regimen (STR) based on ABC/3TC/DTG could be used as simplification strategy in subjects with sustained viral suppression, as the high genetic barrier of DTG should ensure a safe switch from both NNRTI or PI based regimens.     

Studies on the stable inhibition of Na+ + K+-ATPase by cassaine.

Exposure of rat brain Na+ + K+-ATPase (ATP phosphohydrolase E.C. 3.6.1.3) to concentrations of cassaine greater than 1 x 10(-4) M resulted in a poorly reversible inhibition of this enzyme. Inhibition did not require the presence of ATP and developed rapidly, but the final amount of inhibition observed was independent of time. The amount of inhibition observed at a given concentration of cassaine was reduced by increasing the concentration of membranes in the system. The inhibition of Na+ + K+-ATPase activity was associated with equivalent inhibition of the phosphorylation and (3H)-ouabain binding reactions of this enzyme, while the uninhibited enzyme was apparently kinetically normal. Concentrations of cassaine which produced this stable inhibition of Na+ + K+-ATPase had no effect on the Mg2+-activated ATPase or the NADH cytochrome-c-reductase activities of crude rat brain microsomal preparations. Cassaine inhibited the cholinesterase activity of rat brain microsomes with a Ki of about 5 x 10(-5) M, but his inhibition was fully reversible. The poorly reversible inhibitory actions of cassaine, thus, appeared specific for Na+ + K+-ATPase. Because this stable pattern of inhibition of the Na+ + K+-ATPase by cassaine required drug concentrations at least one hundred-fold greater than those which produce positive inotropic effects, it appears unlikely that this pattern of Na+ + K+-ATPase inhibition is involved in the cardiotonic actions of this drug.     

Specific activity and sensitivity to strophanthin of the Na+ + K+-activated ATPase in rats and guinea-pigs with hypoadrenalism

Summary In adrenalectomised rats and in guinea-pigs pretreated with metyrapone the specific activity of the Na⁺ + K⁺-stimulated ATPase of heart and kidney is significantly diminished, whereas the activity of the Mg⁺⁺-ATPase remains unchanged. The specific activity of the Na⁺ + K⁺-stimulated ATPase from brain tissue is not influenced by either adrenalectomy or by treatment with metyrapone.The sensitivity of the Na⁺ + K⁺-stimulated ATPase of heart, brain and kidney to k-strophanthin remains unchanged by adrenalectomy or by treatment with metyrapone.Supported by the Deutsche Forschungsgemeinschaft (SFB 30, Kardiologie).