共查询到18条相似文献,搜索用时 109 毫秒
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目的:探讨利拉鲁肽( Li)对高糖诱导近端小管上皮细胞( PTEC)的保护作用。方法体外原代培养大鼠PTEC。将细胞分为正常对照组、模型对照组、Li小剂量组、Li中剂量组、Li大剂量组,每组设6个复孔,作用72 h后液闪法测定PTEC钠钾ATP酶活性;Western blot测定Toll样受体4(TLR4)蛋白表达;酶联免疫吸附(ELISA)法测定细胞培养上清白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)、纤溶酶原激活物抑制剂-1(PAI-1)。结果与正常对照组比较,高糖培养72 h PTEC钠钾ATP酶活性[(2737.88±317.22)μmol·g-1·h-1]升高,细胞和培养液中TLR4蛋白表达、IL-6、TNF-α和PAI-1增加,均差异有统计学意义(P<0.05或P<0.01);与模型对照组比较,Li中、大剂量组作用72 h 后PTEC钠钾ATP酶活性[(2487.76±215.54),(2301.55±207.63)μmol·g-1·h-1]明显降低,细胞和培养液中TLR4蛋白表达、IL-6、TNF-α和PAI-1降低,均差异有统计学意义(P<0.05或P<0.01)。结论 Li在一定程度上抑制高糖环境炎症细胞因子表达并能稳定钠钾ATP酶活性,可能对肾脏有一定的保护作用。 相似文献
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目的探讨灯盏花素对糖尿病大鼠肾小动脉的影响。方法选健康雄性昆明种SD大鼠70只,随机分为正常对照组(C)20只、糖尿病组(A)和糖尿病灯盏花治疗组(B)各25只。链脲菌素(streptozotocin,STZ)诱导建立糖尿病肾病大鼠模型,B组灯盏花素20mg·kg-1·d-1腹腔内注射,A组和C组等量生理盐水腹腔内注射,3组给药后2W和6W宰杀,收集血检测TGF-β1,肌酐和尿素氮水平,肾组织标本检测NF-κB,肾组织HE,PAS染色比较各组肾小球系膜增生与间质小动脉的硬化情况。结果 1.肾小球系膜增生与间质小动脉的硬化糖尿病组〉灯盏花组〉正常组,(P〈0.01);2.肾组织NF-κB,血TGF-β1、肌酐和尿素氮水平为糖尿病组〉灯盏花组〉正常组,(P〈0.01)。结论高血糖可促进糖尿病大鼠肾脏肥大、肾小球系膜增生和间质小动脉硬化,影响肾功能。灯盏花素可通过对肾组织NF-κB及TGF-β1表达的影响,抑制糖尿病大鼠肾脏肥大、肾小球系膜增生和间质小动脉硬化,发挥保护肾功能。 相似文献
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目的探讨灯盏花素对糖尿病大鼠转化生长因子-β1(TGF-β1)表达和肾功能的影响。方法选健康雄性昆明种SD大鼠70只,随机分为正常对照组(N)20只、糖尿病组(DM)和灯盏花治疗组(EB)各25只,后两组用链脲菌素(streptozotocin,STZ)诱导建立糖尿病肾病大鼠模型,EB组行灯盏花素20mg·k^g-1·d^-1腹腔内注射,N组和DM组行等量生理盐水腹腔内注射,三组给药后2w和6w宰杀,收集标本检测尿肌酐、血糖、血肌酐、尿素氮和血清TGF-β1,观察各组肾小球平均面积(AC)和体积(VC)的变化。结果①TGF-β1比较:糖尿病组〉灯盏花组〉正常组;②灯盏花组及糖尿病组与正常组相比体重下降,肾指数、肾小球面积、体积升高,且灯盏花组较糖尿病组体重增加,肾指数、肾小球面积、体积下降(P〈0.05);③血尿素氮、肌酐比较:糖尿病组〉灯盏花组〉正常组,灯盏花组较糖尿病组降低,且肌酐降低以2w组更明显(P〈0.01)。结论灯盏花素能够抑制糖尿病大鼠血清TGF-β1的表达和肾脏肥大。 相似文献
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灯盏花素对糖尿病大鼠肾组织巨噬细胞浸润的影响 总被引:9,自引:4,他引:9
目的探讨灯盏花素对糖尿病大鼠肾组织巨噬细胞浸润的影响。方法建立STZ诱导的单侧肾切除糖尿病模型,随机分:对照组、模型组、灯盏花素给药组与MMF给药组。8wk末检测尿白蛋白排泄率(AER)、肾组织蛋白激酶C(PKC)活性,应用免疫组化方法检测肾组织ED1及单核细胞趋化蛋白1(MCP1)与细胞间黏附因子1(ICAM1)表达。结果灯盏花素或MMF给药组大鼠肾重、肾重/体重、AER明显低于模型组(P<0.05)。模型组肾组织细胞浆、细胞膜及细胞总PKC活性明显高于对照组(P<0.01),灯盏花素给药组肾组织PKC活性明显低于模型组(P<0.05),MMF给药组肾组织PKC活性与模型组相比无差异。模型组肾小球ED1阳性细胞数及MCP1、ICAM1表达明显高于对照组(P<0.01),灯盏花素或MMF给药可明显缓解这些变化(P<0.05)。结论灯盏花素对糖尿病大鼠肾脏有明显保护作用,其机制可能部分与抑制肾组织巨噬细胞浸润有关。 相似文献
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冰片对灯盏花素在大鼠体内药动学的影响 总被引:2,自引:0,他引:2
目的:观察冰片对灯盏花素在大鼠体内药动学的影响。方法:建立高效液相色谱(HPLC)方法测定大鼠血浆中灯盏乙素的浓度。大鼠尾静脉注射灯盏花素注射液(灯盏乙素24 mg.kg-1)及灯盏花素冰片注射液(灯盏乙素24 mg.kg-1 冰片0.96 mg.kg-1),用HPLC法测定大鼠给药后不同时间血浆灯盏乙素的浓度,BAPP数据处理软件计算药动学参数。结果:灯盏乙素在0.05~60μg.mL-1范围内线性良好(r=0.999 4)。灯盏花素与冰片配伍给药可使灯盏花素中灯盏乙素的药动学参数t1/2α,t1/2β和t1/2γ较单独给药时明显减小[t1/2α:(1.87±0.14)vs(3.46±0.45),P<0.01;t1/2β:(11.18±2.07)vs(14.74±2.89),P<0.05;t1/2γ:(53.31±8.21)vs(161.16±15.48),P<0.01],而K12较单独给药时明显增大[(0.120±0.042)vs(0.039±0.037),P<0.05]。结论:冰片可加快灯盏花素在大鼠体内的分布与消除。 相似文献
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灯盏花素对糖尿病大鼠肾脏氧化应激的影响 总被引:25,自引:6,他引:25
目的 在链脲菌素诱导的糖尿病大鼠模型上 ,灯盏花素与化学合成药氨基胍相比较来探讨灯盏花素对糖尿病大鼠肾脏的保护作用及与氧化应激的关系。方法 用链脲菌素诱导糖尿病大鼠模型后 ,将糖尿病大鼠分为 :糖尿病组、灯盏花素组 (0 1g·kg-1)和氨基胍组 (饮水含 1g·L-1的氨基胍 )。在给药 15~ 17wk后进行与氧化应激相关的各项实验观察。结果 ① 15~ 17wk的糖尿病大鼠与正常对照组相比 :肾指数显著增加 ,肾脏的抗氧化能力显著降低且氧化应激增强。②灯盏花素组与糖尿病组相比 :肾指数显著降低 ,总抗氧化能力和肾脏超氧化物歧化酶活性显著提高 ,脂质过氧化产物丙二醛显著降低。③氨基胍组与糖尿病组相比 :肾脏超氧化物歧化酶活性显著提高 ,肾脏的脂质过氧化产物丙二醛显著性降低 ,总抗氧化能力差异无显著性。结论 糖尿病大鼠与正常大鼠相比肾脏抗氧化能力降低且氧化应激增强 ,灯盏花素可显著提高糖尿病大鼠肾脏的抗氧化能力和降低氧化应激 相似文献
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灯盏花注射液对糖尿病微血管病变的影响 总被引:7,自引:0,他引:7
徐洁 《中国医院药学杂志》2003,23(3):159-160
目的:观察灯盏花注射液对糖尿病微血管病变的影响。方法:选择糖尿病微血管病变患者33例,随机分为2组,治疗组23例用灯盏花注射液加基础治疗,对照组10例用基础治疗,观察治疗前后患者血浆内皮素(ET)、血栓素B2(TXB2)、6-酮-前列腺素F1α(6-K-PGF1α)变化。结果:治疗组和对照组比较,ET、TXB2明显降低(P<0.05),6-K-PGF1α明显升高(P<0.01),结论:灯盏花注射液对6-K-PGF1α微血管病变有较好的治疗作用。 相似文献
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K. Jeevaratnam 《Archives of toxicology》1995,69(10):694-697
The present study describes the effect of methyl isocyanate (MIC) on rabbit cardiac microsomal Na+, K+-ATPase. Addition of MIC in vitro resulted in dose-dependent inhibition of Na+, K+-ATPase, Mg2+-ATPase and K+-activated p-nitrophenyl phosphatase (K+-PNPPase). Activation of Na+, K+- ATPase by ATP in the presence of MIC showed a decrease in Vmax with no change in Km. Similarly, activation of K+ PNPPase by PNPP in the presence of MIC showed a decrease in Vmax with no change in Km. The circular dichroism spectral studies revealed that MIC interaction with Na+, K+-ATPase led to a conformation of the protein wherein the substrates Na+ and K+ were no longer able to bind at the Na+- and K+-activation sites. The data suggest that the inhibition of Na+, K+-ATPase was non-competitive and occurred by interference with the dephosphorylation of the enzyme-phosphoryl complex.
Received: 3 November 1994/Accepted: 23 February 1995 相似文献
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白术水煎剂对老龄大鼠心肌Na~+,K~+-ATPase和血清TAA的影响 总被引:1,自引:0,他引:1
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. 相似文献
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Following the bilateral occlusion of common carotid arteries in gerbil, an increase in water content and sodium/potassium ratio as well as the inhibition of Na+-K+-ATPase was found. The xanthine derivative propentofylline (HWA 285) [3-methyl-1-(5-oxohexyl)-7-propylxanthine] given either before or after cerebral ischemia attenuated the development or postischemic brain swelling and the increase in sodium/potassium ratio and prevented the postischemic reduction of Na+-K+-ATPase activity. It is concluded that the action of propentofylline on brain edema during ischemia is mediated aside from other possible mechanism(s), by the influence of the drug on Na+-K+-ATPase activity. 相似文献
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Oligomycin inhibits Na+,K+-ATPase activity by stabilizing the Na+ occlusion but not the K+ occlusion. To locate the binding domain of oligomycin on Na+,K+-ATPase, the tryptic-digestion profile of Na+,K+-ATPase was compared with the profile of Na+ occlusion within the digested Na+,K+-ATPase in the presence of oligomycin. The Na+ occlusion profile is responsible for the digestion profile of the -subunit, which is the catalytic subunit of the ATPase. The effect of oligomycin on chimeric Ca2+-ATPase activity was examined. The chimera used, in which the 163 N-terminal amino acids of chicken sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1 were replaced with the 200 N-terminal amino acids of the chicken Na+,K+-ATPase 1-subunit, partially retains the Na+-dependent characteristics of Na+,K+-ATPase, because the chimeric Ca2+-ATPase activity is activated by Na+ but inhibited by ouabain, a specific inhibitor of Na+,K+-ATPase (Ishii, T., Lemas, M.V., Takeyasu, K., 1994, Proc. Natl. Acad. Sci. U. S. A., 91, 6103–6107). Oligomycin depressed the activation by Na+ of the chimeric Ca2+-ATPase activity. These findings suggest that the 200 N-terminal amino acids of the Na+,K+-ATPase -subunit include a binding domain for oligomycin. 相似文献
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Changjian Chen Mustafa F. Lokhandwala 《Naunyn-Schmiedeberg's archives of pharmacology》1993,347(3):289-295
Summary Endogenous kidney dopamine (DA) causes natriuresis and diuresis, at least partly, via inhibition of proximal tubular Na+,K+-ATPase. The present study was done to identify the dopamine receptor subtype(s) involved in dopamine-induced inhibition of Na+,K+-ATPase activity. Suspensions of renal proximal tubules from Sprague-Dawley rats were incubated with dopamine, the DA-1 receptor agonist fenoldopam or the DA-2 receptor agonist SK&F 89124 in the presence or absence of either the DA-1 receptor antagonist SCH 23390 or the DA-2 receptor antagonist domperidone. Dopamine and fenoldopam (10–5 to 10–8 mol/1) produced a concentration-dependent inhibition of Na+,K+-ATPase activity. However, SK&F 89124 failed to produce any significant effect over the same concentration range. Incubation with fenoldopam (10–5 to 10–8 mol/1) in the presence of SK&F 89124 (10–6 mol/l) inhibited Na+,K+-ATPase activity to a degree similar to that with fenoldopam alone. Furthermore, DA-induced inhibition of Na+,K+-ATPase activity was attenuated by SCH 23390, but not by domperidone. Since -adrenoceptor activation is reported to stimulate Na+,K+-ATPase activity and, at higher concentrations, dopamine also acts as an a-adrenoceptor agonist, the potential opposing effect from -adrenoceptor activation on DA-induced inhibition of Na+,K+-ATPase activity was investigated by using the -adrenoceptor blocker phentolamine. We found that, in the lower concentration range (10–5 to 10–7 mol/1), dopamine-induced inhibition of Na+,K+-ATPase activity in the presence of phentolamine was similar in magnitude to that observed with dopamine alone. However, at the highest concentration used (10–4 mol/1), dopamine produced a significantly larger degree of inhibition of Na+,K+-ATPase activity in the presence of phentolamine. These results indicate that the DA-1 dopamine receptor subtype, but not the DA-2 receptor subtype, is involved in dopamine-mediated inhibition of Na+,K+-ATPase. At higher concentrations of dopamine, the DA-1 receptor-mediated inhibitory effect on Na+,K+-ATPase activity may be partly opposed by a simultaneous -adrenoceptor-mediated stimulation of the activity of this enzyme. 相似文献
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James Henry Zavecz 《European journal of pharmacology》1986,120(3):363-366
In electrically stimulated rabbit ventricular strips, theophylline (0.3–30 M) antagonized the increased contractility produced by ouabain (0.8 μM). Initial velocity of specific [3H]ouabain binding to homogenates prepared from the muscle strips was used to determine the fraction of binding sites occupied by ouabain. Theophylline decreased the binding of ouabain to (Na+ + K+)-ATPase. It is concluded that the effect of theophylline on ouabain-induced positive inotropism may be mediated by decreased ouabain binding to (Na+ + K+)-ATPase. 相似文献