一氧化氮在糖尿病大鼠合并肾病中的变化及意义

目的 :观察一氧化氮 (NO)在糖尿病大鼠合并肾病中的变化及意义。方法 :复制糖尿病肾病病变 (DN)大鼠模型 ,采用硝酸还原酶法测定尿液及肾组织匀浆中 NO含量。结果 :尿液中 NO含量变化为糖尿病肾病组高于正常组 (NC组 )(P<0 .0 1) ,而治疗组 (INS组 )与 DN组比较两组间无差异 (P >0 .0 5 ) ;肾组织匀浆中 NO含量变化为 DN组高于 NC组(P<0 .0 1) ,而 INS组高于 DN组 (P <0 .0 1)。结论 :NO在介导 DN的肾小球高滤过中有重要作用     

糖尿病肾病病人血浆心钠素及内皮素含量分析

目的　比较糖尿病肾病 (DN)病人治疗前后心钠素 (ANP)、内皮素 (ET 1)含量的变化。方法　用放射免疫法测定 4 3例糖尿病 (DN)和 2 0例正常对照组血浆ANP、ET 1的含量。结果　DN组血浆ANP和ET 1浓度明显高于正常对照组 (P <0 0 5 ) ;ANP、ET 1在治疗前含量最高 ,治疗后下降 ;治疗组治疗 12个月后ANP、ET 1含量较常规组下降 ,差异有显著意义 (P <0 0 5 )。结论　糖尿病肾病病人治疗前后心钠素及内皮素含量的改变 ,可能与糖尿病肾病的发生和发展有关。     

葛根素在糖尿病肾病病人中的药动学

目的 :比较葛根素在健康人及不同临床期糖尿病肾病 (DN)病人体内的药动学。方法 :健康人7例为NC组 ,DN组 2 0例 (其中临床早期 10例 ,为DN1组 ;中期 10例 ,为DN2 组 )单次静脉滴注葛根素 (5mg·kg- 1,6 0min内滴完 )后 ,用高效液相色谱法测定血清药物浓度 ,3P87程序拟合计算。结果 :DN2 组较NC组和DN1组药物T12 β延长 ;清除率(Cl)下降 ;5min及 5h的药物浓度 (C)下降延缓。NC组与DN1组比较差异无显著意义 (P >0 .0 5 )。表观分布容积 (Vd)DN各组较NC组减少 (P <0 .0 5和P <0 .0 1)。结论 :不同临床期的DN病人 ,葛根素体内药动学过程有明显不同     

糖尿病大鼠不同病程血清一氧化氮含量的变化及其意义

目的 :观察不同病程糖尿病大鼠血清一氧化氮 (NO)含量变化 ,探讨糖尿病大鼠血清 NO变化的规律和意义。方法 :分别在第、4、7、10周 3个时期测定糖尿病大鼠与正常对照大鼠血糖及血清的 NO水平。结果 :(1)血糖变化对照组各时期血糖值维持在正常水平 ;糖尿病组大鼠各时期血糖均明显高于对照组 (P <0 .0 5 )。 (2 )血清 NO浓度变化对照组各时期血清 NO浓度无显著性差异 ;糖尿病组大鼠 4周时血清 NO浓度明显高于对照组 (P <0 .0 5 ) ;7周、10周时糖尿病组大鼠血清 NO浓度恢复到正常水平 ,与对照组相比无显著差异 (P >0 .0 5 )。结论 :NO是糖尿病发生的重要体液因子之一 ,但可能与血糖的调节无关。     

虫草菌丝对实验性肝硬化大鼠肝组织胰岛素酶活性的影响

目的 :探讨虫草菌丝对实验性肝硬化大鼠肝组织匀浆上清液胰岛素酶活性的动态影响及其可能机制。方法 :以CCl4诱导大鼠肝硬化模型 ,设立正常组、模型组和虫草组。正常组于实验开始时便处死大鼠 ,而后 2组则于造模 3 ,6,9wk分批处死 ,取血及肝组织标本。生化法测定血清丙氨酸转氨酶(ALT)、清蛋白 (ALB)含量 ,放射免疫法测定血清透明质酸 (HA)、血清胰岛素 (INS)含量及肝组织匀浆上清液的胰岛素酶活性。结果 :(1 ) 3 ,6wk虫草组大鼠血清ALT ,ALB及HA含量与对应模型组差异无显著意义 (P >0 .0 5 ) ,9wk虫草组大鼠血清ALT ,HA含量显著低于对应模型组 (P <0 .0 5 ) ,而其血清ALB含量则显著高于对应模型组 (P<0 .0 5 ) ;(2 ) 3wk虫草组及模型组大鼠血清INS水平及肝组织胰岛素酶活性与正常组大鼠差异无显著意义 (P >0 .0 5 ) ,6,9wk虫草组及模型组大鼠血清INS水平显著高于正常组 (P <0 .0 5 ) ,而对应的肝组织胰岛素酶活性则显著低于正常组 (P <0 .0 5 ,或P <0 .0 1 ) ;(3 ) 3 ,6,9wk虫草组大鼠血清INS水平及肝组织胰岛素酶活性与对应模型组差异无显著意义(P >0 .0 5 )。结论 :虫草菌丝可减轻CCl4对肝细胞的损伤 ,并可抑制肝纤维化 ;造模 6wk后实验性肝硬化大鼠肝组织胰岛素酶活性开始降低 ,血清INS含量开始升高     

阿司匹林对糖尿病肾病大鼠血液流变学的影响

目的通过复制大鼠糖尿病肾病模型,探索阿司匹林对糖尿病肾病大鼠血液流变学的影响。方法取健康SD大鼠30只,随机选取24只,给予一次性腹腔注射链脲佐菌素(STZ)50mg/kg,其余大鼠作为正常对照(NC)组。72h后断尾取血测血糖(≥16.7mmol/L)确定糖尿病模型建立,造模成功22只。随机将模型组大鼠分为糖尿病肾病组(DN组)和阿司匹林治疗(DN+A)组,各11只,(DN+A)组灌胃阿司匹林40mg/(kg.d),DN组和NC组应用相同体积生理盐水。灌胃12周后,断尾测空腹血糖,然后腹腔注射10%水合氯醛麻醉大鼠,腹主动脉取血6mL。用苦味酸法测定血肌酐,用二乙酰一肟显色法测定尿素氮含量,用全自动血流变快测仪测血液流变学指标。结果与NC组比较,DN组大鼠明显消瘦,体重减轻,多饮、多食、多尿明显,FBG明显升高(P<0.01),BUN、SCr显著升高(P<0.01),全血高、中、低切黏度和血浆黏度均显著升高(P<0.01),红细胞聚集指数明显升高(P<0.05);与DN组比较,(DN+A)组FBG水平稍有降低,但无明显差异(P>0.05),BUN、SCr水平明显降低(P<0.05),(DN+A)组全血高、中、低切黏度和血浆黏度均明显降低(P<0.05),红细胞聚集指数明显降低(P<0.05)。结论糖尿病肾病大鼠的全血黏度、血浆黏度和红细胞聚集指数明显升高,适量的阿司匹林能够改善糖尿病肾病大鼠的血液流变学情况。     

沃丽汀对糖尿病肾病大鼠CGRP与VEGF的影响

目的观察沃丽汀对糖尿病肾病大鼠肾脏的保护作用，并探讨其作用机制。方法将雄性Wistar大鼠随机分为正常对照组（NC组），糖尿病肾病组（DN组）和沃丽汀治疗组（D＋J组）各10只。DN组与D＋J组采用链脲佐菌素（STZ）诱导制作糖尿病大鼠模型。模型制作成功后，NC组与DN组给予0.9%氯化钠溶液10 mL&#8226;kg 1灌胃，D＋J组于模型制作成功后第3天开始给予沃丽汀灌胃，0.9 mg&#8226;kg 1&#8226;d 1。8周后采用放免法检测大鼠血浆降钙素基因相关肽（CGRP）含量，免疫组织化学方法检测肾小球血管内皮生长因子（VEGF）表达情况，同时检测24 h尿清蛋白排泄率（24 hUAER）、尿肌酐清除率（Ccr）、肾重指数（KMI）、体重及血糖。结果与NC组比较，DN组血浆中CGRP水平、Ccr及体重均显著降低（均P＜0.01），24 hUAER、KMI、肾脏VEGF表达及血糖均显著升高（均P＜0.01）。与DN组比较，D＋J组CGRP水平差异无显著性，Ccr显著升高（P＜0.05），肾脏VEGF表达显著降低（P＜0.01）。结论沃丽汀对糖尿病肾病大鼠血浆CGRP水平无显著影响，但能抑制肾组织VEGF表达，一定程度上延缓糖尿病肾病发展。     

糖尿病大鼠肾皮质α平滑肌肌动蛋白表达与肾病发生的关系

目的　探讨早期抑制纤维化能否阻止大鼠糖尿病肾病的发生。方法　将72只SD大鼠随机分为3组:正常对照组、糖尿病组和干扰素γ(IFNγ)组。除正常对照组外,其余两组采用一次性ip链佐星70mg·kg- 1 ·d- 1 制备糖尿病模型。IFNγ组的糖尿病大鼠scIFNγ( 1 0 0kU·kg- 1 ·d- 1 )共8周。第1 ,2 ,4 ,8周每组各取6只大鼠,分别测定血糖、肾脏肥大指数、尿白蛋白,免疫组化法测定肾组织α平滑肌肌动蛋白(αSMA)和Ⅳ型胶原的表达,同时以酶联免疫吸附法测定肾皮质αSMA的含量。结果　第1 ,2 ,4 ,8周,IFNγ组大鼠肾皮质αSMA含量分别较糖尿病组减少3 6.9%,4 4.4 %,60 .4 %和4 0 .6%(P <0 .0 5 )。但IFNγ组肾脏Ⅳ型胶原表达、肾脏肥大指数均高于正常对照组(P <0 .0 1 ) ,与糖尿病组无显著性差异(P>0 .0 5 )。结论　该剂量IFNγ抑制肾组织αSMA表达,但不能阻止糖尿病肾病早期病变的发生     

甲磺酸氨氯地平对糖尿病肾病血浆内皮素1的影响

目的观察氨氯地平对糖尿病肾病(DN)患者血浆内皮素-1(ET-1)的影响。方法 56例糖尿病肾病患者给予常规治疗8周后根据尿白蛋白排泄率分为早期糖尿病肾病组(DN1组)及临床糖尿病肾病组(DN2组),应用甲磺酸氨氯地平每次5mg,每日2次,观察给药前及给药后8周、12周的血浆ET-1及UAER。结果治疗前DN2组ET-1、UAER较DN1组显著升高,两两比较差异有统计学意义(P<0.01);治疗8周及12周后两组ET-1均较治疗前明显下降,差异有统计学意义(P<0.05);治疗8周及12周后两组UAER虽较治疗前下降,但无统计学差异(P>0.05)。糖尿病肾病患者ET-1与UAER水平呈正相关(r=0.62,P<0.05)。结论糖尿病肾病患者尿白蛋白排泄与血管内皮功能有一定相关性,氨氯地平有明显的内皮保护作用,可以作为糖尿病肾病治疗药物的选择。     

氯沙坦对实验性糖尿病大鼠肾脏功能的保护作用

目的 :探讨氯沙坦对糖尿病肾病肾脏功能的保护作用。方法 :制作糖尿病大鼠模型 ,分成 3组 ,每组 15只 ,糖尿病治疗组给予氯沙坦灌胃 ,糖尿病组和正常对照组均给予等量生理盐水灌胃。分别于实验的wk 1,2 ,4取材 ,测定血糖、血肌酐、尿清蛋白、尿肌酐、尿α1 微球蛋白排泄率和血浆内皮素(ET)水平。结果 :糖尿病组大鼠出现血糖升高、肌酐清除率下降、尿清蛋白和尿α1 微球蛋白排泄率升高 ,与正常对照组相比差异有非常显著和显著意义(P <0 .0 1或P <0 .0 5 ) ,血浆ET水平升高 ,wk 2时与正常对照组间差异有非常显著意义 ;肌酐清除率、尿清蛋白和尿α1 微球蛋白排泄率等指标 ,治疗组与糖尿病组比较差异均有显著或非常显著意义。结论 :动物实验证实氯沙坦可减轻糖尿病肾病的肾功能损害 ,改善肾功能 ,具有肾脏保护作用     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data.     

Effects of Nitro-L-Arginine on Blood Pressure and Cardiac Index in Anesthetized Rats: A Pharmacokinetic-Pharmacodynamic Analysis

Purpose. Nitric oxide synthase (NOS) inhibitors such as Nitro-L-arginine (L-NA) are being considered for the management of hypotension observed in septic shock. However, little information is available regarding the pharmacokinetic and pharmacodynamic properties of these agents. Our objective was to examine the relationships between L-NA plasma concentration and various hemodynamic effects such as cardiac index (CI), mean arterial pressure (MAP), and heart rate (HR) elicited by L-NA administration in rats. Methods. L-NA was infused at doses between 2.5 – 20 mg/kg/hr in anesthetized rats over one hour. Hemodynamic effects and plasma L-NA levels were determined. Results. Infusion of L-NA resulted in dose-dependent increases in MAP and systemic vascular resistance (SVR), decreases in CI, and minimal change in HR. The relationships between the hemodynamic effects and plasma L-NA levels were not monotonic, and hysteresis was observed. Using nonparametric analysis, the equilibration half-time (t_1/2,keo) between plasma L-NA and the hypothetical effect site was determined to be 51.5 ± 6.6 min, 42.4 ± 10.1 min, 43.4 ± 9.0 min for MAP, CI, and SVR, respectively (n = 14). The E_max and EC₅₀ values obtained were + 32.5 ± 8.4 and 2.6 ± 1.3 g/ml for MAP and –52.9 ± 15.6 and 3.7 ± 1.8 g/ml for CI, respectively. Conclusions. Although L-NA can bring about beneficial elevation of MAP, such effect is always accompanied by a stronger effect on CI depression. Dose escalation of L-NA may bring about detrimental negative inotropic effect and loss of therapeutic efficacy.     

HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

洛美沙星体内外抗菌活性研究

洛美沙星对革兰氏阴性菌具有强的抑菌活力。对克氏肺炎杆菌的抗菌活性最强,MIC_(50)为0.12mg/L;对痢疾杆菌、产气杆菌、粘质沙雷氏菌、不动杆菌和枸椽酸杆菌的MIC_(50)分别为1和4mg/L。洛美沙星对肠细菌科细菌的活力比诺氟沙星和依诺沙星强2～16倍,明显地比丁胺卡那霉素、庆大霉素强。对金葡球菌MIC_(50)为1mg/L, MRSA对洛美沙星同样敏感。洛美沙星对表葡球菌、链球菌、粪链球菌及肺炎双球菌等的抗菌活性与地氟沙星相似,比诺氟沙星、依诺沙星、丁胺卡那霉素、庆大霉素和头孢三嗪分别强2～4倍。 洛美沙星对小鼠全身感染的疗效优于诺氟沙星。对大肠杆菌、克氏肺炎杆菌和绿脓杆菌感染小鼠iv的ED_(50)分别是0.74、0.13和3.45mg/kg, po的ED_(50)分别是0.94、1.46和6.20mg/kg。     

The pathogenesis of,and pharmacological treatment for,Canavan disease

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Protective role of exogenous α-lipoic acid (ALA) on hippocampal antioxidant status and memory function in rat pups exposed to sodium arsenite during the early post-natal period

The present work focussed on the effect of exogenous α-lipoic acid (ALA) administration on retention memory and oxidative stress markers in the hippocampus subsequent to early post-natal exposure of rat pups to sodium arsenite (NaAsO₂). Wistar rat pups were divided into the control groups receiving either no treatment (Ia) or distilled water by intraperitoneal route (i.p.) (Ib) and the experimental groups receiving either NaAsO₂ alone (1.5 and 2.0?mg/kg body wt.) (IIa, IIb) or NaAsO₂ (1.5 and 2.0?mg/kg body wt.) followed by ALA (70?mg/kg body wt.) (IIIa, IIIb) (i.p.) from post-natal day (PND) 4–15. The initial and retention transfer latency (ITL and RTL) was determined on PND 14 and 15 using elevated plus maze. The animals were sacrificed by cervical decapitation (PND 16) and the brains were obtained. The dissected out hippocampus was processed for estimation of oxidative stress markers, glutathione (GSH), and superoxide dismutase (SOD). NaAsO₂ exposure resulted in longer RTL in animal groups IIa and IIb, thereby suggestive of arsenic-induced impairment in retention memory. RTL was significantly shorter in animal groups (IIIa, IIIb) receiving ALA following NaAsO₂, thereby suggestive of improvement in retention memory. GSH and SOD levels were significantly decreased in animals receiving NaAsO₂ alone as against group Ib and administration of ALA following NaAsO₂ increased the levels of hippocampal GSH and SOD. These observations are suggestive of the role of exogenous ALA in ameliorating the adverse effects induced by NaAsO₂ exposure of rat pups on retention memory and oxidative stress markers.     

乙酰吉他霉素临床前药理学研究

乙酰吉他霉素对临床分离的革兰氏阳性球菌有较好的抑菌活力，其对金葡球菌、β－溶血性链球菌、表葡球菌的ＭＩＣ_（５０）分别为１、０．２２和４ｍｇ／Ｌ，对耐红霉素、青霉素的金葡球菌、表葡球菌半数以上较敏感，与吉他霉素相似，但其对革兰氏阴性菌无明显作用。乙酰吉他霉素对小鼠实验性细菌感染有明显保护作用。对金葡球菌、肺炎双球菌感染小鼠口服用药的ＥＤ_（５０）分别为７９．６和２５．１ｍｇ／ｋｇ。其疗效与吉他霉素、麦白霉素、乙酰螺旋霉素相似。乙酰吉他霉素小鼠１次口服的ＬＤ_（５０）＞１５ｇ／ｋｇ，与吉他霉素相比毒性无差异。     

大鼠溃疡性结肠炎模型的实验研究

目的对不同剂量的三硝基苯磺酸（ＴＮＢＳ）引起的大鼠溃疡性结肠炎（ＵＣ）模型进行观察和评价。方法采用一次性直肠注入大鼠ＴＮＢＳ（２５～１５０ｍｇ·ｋｇ－１）的３０％乙醇溶液，引起慢性炎症性肠疾病（ＩＢＤ），３ｗｋ后外死动物对各剂量下动物结肠的重量、髓过氧化物酶（ＭＰＯ）活性及组织形态学变化进行观察和评价。结果ＴＮＢＳ在１００～１５０ｍｇ·ｋｇ－１剂量下引起的ＵＣ肠壁明显增厚，炎症和溃疡至少维持７ｗｋ时间，ＭＰＯ活性值显著性升高，组织学检查发现粘膜及粘膜下层有大量中性粒细胞及淋巴细胞、巨噬细胞、纤维细胞浸润，肉芽组织及隐窝脓肿形成，５０ｍｇ·ｋｇ－１剂量时有一较轻度的损伤。２５ｍｇ·ｋｇ－１时对结肠的重量、ＭＰＯ活性及损伤指数都没有显著性改变（Ｐ＞０．０５）。结论用ＴＮＢＳ引起大鼠实验性ＵＣ，其溃疡和炎症维持一较长时间，这一病理特征为炎症性疾病防治药物的研究提供了条件；本模型的最佳剂量为１００ｍｇ·ｋｇ－１左右     

Dinoflagellate polyether within the yessotoxin, pectenotoxin and okadaic acid toxin groups: Characterization, analysis and human health implications

Diarrhetic Shellfish Poisoning (DSP) is a specific type of food poisoning, characterized by severe gastrointestinal illness due to the ingestion of filter feeding bivalves contaminated with a specific suite of toxins. It is known that the problem is worldwide and three chemically different groups of toxins have been historically associated with DSP syndrome: okadaic acid (OA) and dinophysistoxins (DTXs), pectenotoxins (PTXs) and yessotoxins (YTXs). PTXs and YTXs have been considered as DSP toxins because they can be detected with the bioassays used for the toxins of the okadaic acid group, but diarrhegenic effects have only been proven for OA and DTXs. Whereas, some PTXs causes liver necrosis and YTXs damages cardiac muscle after intraperitoneal injection into mice. On the other hand, azaspiracids (AZAs) have never been included in the DSP group, but they cause diarrhoea in humans. This review summarizes the origin, characterization, structure, activity, mechanism of action, clinical symptoms, method for analysis, potential risk, regulation and perspectives of DSP and associated toxins produced by marine dinoflagellates.     

Latent role of in vitro Pb exposure in blocking Aβ clearance and triggering epigenetic modifications

Both β-amyloid (Aβ) catabolism and epigenetic regulation play critical roles in the onset of neurodegeneration. The latter also contribute to Pb neurotoxicity. The present study explored the role of epigenetic modifiers and Aβ degradation enzymes in Pb-induced latent effects on Aβ overproduction in vitro. Our results indicated that in SH-SY5Y cells exposed to Pb, the expression of NEP and IDE remained declined during the recovery period, accompanied with abnormal increase of Aβ_1-42 and amyloid oligomer. A disruption of selective global post-translational histone modifiers including the decrease of H3K9ac and H4K12ac and the induction of H3K9me2 and H3K27me2 dose dependently was also showed in recovery cells. Moreover, histone deacetylase inhibitor VPA could attenuate latent Aβ accumulation and HDAC activity induced by Pb, which might be by regulating the expression of NEP and IDE epigenetically. Overall, our results suggest sustained reduction of NEP and IDE expression in response to Pb sensitizes recovery SH-SY5Y cells to Aβ accumulation; however, administration of VPA is demonstrated to be beneficial in modulating Aβ clearance.