氨氯地平和依那普利对高血压大鼠肾损害的防治效果观察

目的　探讨钙拮抗剂氨氯地平 ( amlodipine)与转换酶抑制剂依那普利 ( enalapril)抗高血压治疗时对肾脏的保护作用。　方法　实验动物为 1 6月龄的自发性高血压大鼠 ( SHR) 3 0只 ,分为氨氯地平组、依那普利组及对照组 ,治疗及观察时间为 3个月。　结果　氨氯地平和依那普利降压效果相似 ,肾功能改变 :老化过程中对照组内生肌酐清除率 ( Ccr)为 ( 0 .0 90± 0 .0 1 0 ) ml· min- 1 ·1 0 0 g- 1体重 ,与实验前的 ( 0 .1 4 9± 0 .0 0 7) ml·min- 1· 1 0 0 g- 1体重比较显著降低 ( P<0 .0 1 ) ;两治疗组 Ccr无明显下降 ( P>0 .0 5) ,依那普利组为 ( 0 .1 57± 0 .0 0 3 ) ml· min- 1 · 1 0 0 g- 1 体重 ,氨氯地平组为 ( 0 .1 63± 0 .0 0 6) ml·min- 1· 1 0 0 g- 1体重。肾功能测验 ,N-乙酰 -β-D-氨基葡萄糖苷酶在对照组逐步增高 ,但两治疗组降低。血浆血管紧张素 水平与肾组织内皮素含量 :依那普利组〔( 2 52 .3± 3 3 .1 )ng/ L、( 1 2 2 .2± 3 3 .5) ng/ L〕与氨氯地平组〔( 1 87.3 2± 53 .1 ) ng/ L、( 1 51 .1± 2 2 .9) ng/ L〕均低于对照组〔( 3 83 .5± 84 .1 ) ng/ L、( 1 85.8± 1 4 .5) ng/ L〕( P<0 .0 1 )。肾病理改变 ,对照组明显重于治疗组。计算机图像分析 ,对照组肾小球系膜     

吸氧对慢性缺氧高二氧化碳大鼠肺血管L-精氨酸转运的影响

目的　探讨慢性缺氧 (O2 )高二氧化碳 (CO2 )对大鼠肺动脉L 精氨酸 (L Arg)转运的影响与吸氧的作用。方法　将 4 0只大鼠以随机区组设计法分成 4组 ,用 0 2mmol/L和 5 0mmol/L [3 H] Arg将肺动脉孵育 ,测定其对 [3 H] L Arg的摄取率、一氧化氮合酶 (NOS)活性与一氧化氮 (NO2 /NO3)含量。每组 1 0只。正常对照组 (A组 )、慢性缺O2 4周后伴高CO2 4周组 (B组 )、慢性缺O2 4周伴高CO24周后吸空气 4周组 (C组 )及慢性缺O2 4周伴高CO2 4周后吸O2 4周组 (D组 )。结果　 (1 )肺动脉平均压 (mPAP)、右心室 (RV)和左心室 +室间隔 (LV +S)重量比值 (RV/LV +S) :B组 (33% )与A组(35 % )比较差异有显著性 (P均 <0 0 1 ) ;D组 (2 4 % )与C组 (2 4 % )比较 ,差异也有显著性 (P均 <0 0 5 )。 (2 )离体孵育的肺动脉摄取低浓度 (0 2mmol/L)和高浓度 (5 0mmol/L) [3 H] L Arg比较 :B组分别为 [(3 0 4± 0 1 6 ) μmol·g-1 min-1 ]、[(8 1 2± 0 1 4 ) μmol·g-1 ·min-1 ],A组分别为 [(4 6 2± 0 5 5 )μmol·g-1 ·min-1 ]、[(1 1 2 4± 1 0 2 ) μmol·g-1 ·min-1 ],A、B两组比较差异有显著性 (P均 <0 0 1 ) ;而D组分别为 [(4 30± 0 1 8) μmol·g-1 ·min-1 ]、[(1 2 31± 0 6 5 ) μmol·g-1 ·m     

黄芩对糖尿病大鼠肾脏病变的影响

目的　探讨中药黄芩对实验性糖尿病大鼠肾脏病变的影响及可能机制。　方法　诱导大鼠糖尿病后 ,随机分为苯拉普利对照组及黄芩治疗组 ,比较各组大鼠的自由基代谢状况、尿白蛋白(Alb)排泄量、肌酐清除率 (Ccr)及肾脏病理改变。　结果　黄芩治疗组肾脏超氧化物歧化酶 (SOD )和过氧化氢酶 (CAT)活性 [分别为 (11.3 9± 1.57)U /mg (pr)和 (1.41± 0 .11)U/g(ww )·min- 1]较对照组 [分别为 (8.69± 1.65)U /mg (pr)和 (1.2 6± 0 .0 8)U·g- 1(ww )·min- 1]明显增高 (P <0 0 5) ,肾脏和尿脂质过氧化物丙二醛 (MDA)水平 [分别为 (2 85± 2 2 )nmol/ g(ww)和 (62 1± 113 )mmol/ 2 4h]较对照组 [分别为 (3 3 0± 2 2 )nmol/ g(ww)和 (989± 2 0 5)mmol/ 2 4h]明显降低 (P <0 0 5)。黄芩治疗组尿Alb排泄量显著减少 ,系膜基质增生和肾脏体积增大明显减轻 ,与苯那普利治疗组无显著差异。　结论　黄芩可通过减轻肾脏自由基代谢紊乱、抑制肾小球高滤过等机制来改善糖尿病大鼠的肾脏病变状况     

药物对体外冲击波碎石术所致老年人急性肾损伤的防护作用

目的　探讨抗氧化维生素联用钙拮抗剂对体外冲击波碎石术 (ESWL)所致老年人急性肾损伤的防护作用。　方法　 6 4例接受ESWL的老年肾结石患者随机分为用药组和对照组 ,每组32例。用药组术前 3d口服维生素E和硝苯地平 ,对照组不用药物。于术前 1d、术后 1d及 1周测定 2 4h尿内皮素 (ET)、丙二醛 (MDA)和N 乙酰 β 葡萄糖苷酶 (NAG)水平 ,同时测定肾内血管阻力指数 (RI)和内生肌酐清除率 (Ccr)。　结果　对照组术后 1dET、MDA、NAG和RI〔分别为 (487 8±2 82 7)ng/L、(16 96± 4 6 3)nmol/L、(44 4 2± 2 3 14 )U·g-1·cr-1和 0 70 4± 0 0 5 8〕比用药组术后 1d〔分别为 (6 9 4 5± 18 7)ng/L、(10 5 5± 6 4 6 )nmol/L、(12 4 2± 6 5 6 )U·g-1·cr-1和 0 6 6 8± 0 0 5 9〕明显增高 (P <0 0 1) ,Ccr〔(1 2 1± 0 2 7)ml/s〕降低幅度高于用药组〔(1 4 2± 0 30 )ml/s〕(P <0 0 1) ;术后 1周MDA、NAG及RI和Ccr仍未恢复术前水平。用药组术后 1dCcr比术前降低 (P <0 0 1) ,但 1周内恢复术前水平 ;ET、MDA、NAG和RI无明显增高 (P >0 0 5 )。　结论　抗氧化维生素联用钙拮抗剂可以减轻ESWL的脂质过氧化作用 ,减少ET的释放 ,对ESWL所致的老年人急性肾损伤有明显防护作用。     

一氧化氮在肝硬化大鼠睾丸功能障碍发生中的作用

目的探讨一氧化氮(NO)在肝硬化睾丸功能障碍发生中的作用. 方法采用胆管结扎(BDL)复制肝硬化模型,应用硝酸酶还原法测定大鼠血清和睾丸组织匀浆的NO浓度,应用放射免疫分析法测定血清睾酮浓度,同时检测大鼠附睾精子密度和精子活率. 结果肝硬化(HC)组大鼠血清和睾丸组织匀浆NO水平分别为(4.165±1.162)μmol/L和(1.305±0.087)μmol/g,假手术(SO)组大鼠血清和睾丸组织匀浆NO水平分别为(0.535±0.237)μmol/L和(0.720±0.063)μmol/g,HC组显著高于SO组.HC组血清睾酮水平[(0.049±0.020)μg/L]、附睾精子活率(16.46%±4.84%)及精子密度[(86.89±33.17)×106个/ml]均显著低于SO组[分别为(2.680±0.403)μg/L、62.45%±9.21%和(299.43±53.85)×106个/ml],而持续给予小剂量NOS抑制剂L-NAME(HC-NAME组)(0.5mg@kg-1@d-1)达一周,HC-NAME组大鼠血清及睾丸组织NO水平分别为(1.975±0.406)μmol/L和(0.950±0.057)μmol/g,较HC组显著降低.同时HC-NAME组血清睾酮水平、附睾精子活率和精子密度较HC组均显著增高,分别为(0.993±0.179)μg/L、33.85%±4.93%和(188.94±38.34)×106个/ml. 结论 NO在肝硬化大鼠睾丸功能障碍发生中起重要作用,小剂量应用NOS抑制剂L-NAME,肝硬化大鼠NOS持续抑制引起的睾丸功能障碍得到不同程度改善,表明在治疗肝硬化睾丸功能障碍患者时体内给予NOS抑制剂的可能性.     

硒对大鼠高碘性I型脱碘酶损伤的干预作用

目的研究高碘性甲状腺损伤的机制并寻求合适的硒干预剂量。方法50只Wistar大鼠分为5组正常组、高碘组(饮水含碘酸钾48mg/L)和3个补硒组(饮水含碘酸钾48mg/L,亚硒酸钠分别为0.5、1.0、2.0mg/L),共喂养36周。放射免疫法测定甲状腺激素水平,测定肝脏和肾脏组织Ⅰ型脱碘酶(IDI)活性,以RT-PCR测定IDImRNA水平。结果与正常组比较,高碘组肝、肾IDI活性[(17.1±2.1,2.67±1.10)pmolI·mg-1·min-1vs(13.0±2.9,1.52±0.44)pmolI·mg-1·min-1]、mRNA水平(1.78±0.14,1.55±0.17vs0.90±0.05,0.58±0.12,均P<0.05)下降(均P<0.05),而补充0.5mg/L硒组上述指标与正常组差异无统计学意义。结论IDI活力、mRNA水平下降可能是高碘性甲状腺损伤的机制之一,而补充硒应选择合适的干预剂量。     

硒对大鼠高碘性Ⅰ型脱碘酶损伤的干预作用

目的研究高碘性甲状腺损伤的机制并寻求合适的硒干预剂量.方法 50只Wistar大鼠分为5组正常组、高碘组(饮水含碘酸钾48 mg/L)和3个补硒组(饮水含碘酸钾48 mg/L,亚硒酸钠分别为0.5、1.0、2.0 mg/L),共喂养36周.放射免疫法测定甲状腺激素水平,测定肝脏和肾脏组织Ⅰ型脱碘酶(IDI)活性,以RT-PCR测定IDI mRNA水平.结果与正常组比较,高碘组肝、肾IDI活性[(17.1±2.1,2.67±1.10)pmol I·mg-1·min-1vs(13.0±2.9,1.52±0.44)pmol I·mg-1·min-1]、mRNA水平(1.78±0.14,1.55±0.17vs0.90±0.05,0.58±0.12,均P＜0.05)下降(均P＜0.05),而补充0.5mg/L硒组上述指标与正常组差异无统计学意义.结论 IDI活力、mRNA水平下降可能是高碘性甲状腺损伤的机制之一,而补充硒应选择合适的干预剂量.     

一氧化氮合酶2抑制剂改善大鼠心肌梗死后心功能的作用

目的 :探讨一氧化氮合酶 2 (NOS2 )改善心肌梗死 (MI)后心功能障碍的作用。方法 :选用选择性NOS2抑制剂S 甲基硫脲 (SMT)抑制NOS2。于MI后 4周观察SMT对心功能的影响。结果 :MI组MI后 4周 ,心肌NOS2表达及血浆一氧化氮 (NO)水平均较假手术组升高 [(0 .2 6 1± 0 .0 2 5 )∶(0 .0 92± 0 .0 11)A·μm-2 ,P<0 .0 5 ];(4 6 .6± 4 .2 )∶(30 .6± 2 .1) μmol/L ,P <0 .0 5 ]。SMT干预 4周可使MI后血浆NO水平降低 [(2 6 .6±2 .2 )∶(4 6 .6± 4 .2 ) μmol/L ,P <0 .0 5 ],心室肥厚减轻 ,MI范围缩小 ,心功能改善 [左室舒张末压 (6 .1± 0 .7)∶(11.0± 1.2 )mmHg(1mmHg =0 .133kPa) ,P <0 .0 5 ];中心静脉压 (0 .8± 0 .1)∶(1.6± 0 .2 )mmHg ,P <0 .0 5 ]。结论 :抑制NOS2可以改善MI后心功能。NOS2及其产物NO在MI后心功能障碍的发生发展过程中起促进作用     

残余肾功能状态对腹膜透析效能的影响

目的:前瞻性观察终末期肾衰(ESRF)患者在腹膜透析(PD)治疗后残余肾功能(RRF)对透析效能及相关临床指标之间的影响。方法:所有患者按残余肾小球滤过率(rGFR)水平将其分为A组(GFR0~2ml/min)、B组(GFR2·1~4ml/min)和C组(GFR>4ml/min)。每3个月进行一次临床随访,全面评估患者的全身情况及透析状态,包括血压、身高、体重、体重指数(BMI)、尿量(UV)、残余肾肌酐清除率(Ccr)、每周总尿素氮表现率(Kt/Vtotal)、每周肌酐总清除率(WCcrtotal)、蛋白氮呈现率(nPNA)、残余肾尿素及Ccr。对比观察不同RRF状态患者透析状况和部分临床及生化指标变化。尿量<100ml/d或Ccr<1·0ml/min视为无尿。结果:三组不同残肾状态患者Kt/vtotal和Ccr分别为1·75±0·35、2·07±0·54、2·46±0·50和53·4±11·2、66·6±11·2、97·6±22·1(L/Wks),各组之间差异非常显著(P<0·001)。三组不同残余肾Kt/v和Ccr分别占总体kt/v的12·4%、27%、45·7%及总体Ccr的18·3%、47·3%和65·3%,三组间相比差异亦显著(P<0·01)。此外,三组间高血压发生率、心胸比例及左心室肥厚(LVH)亦存在一定差异,C组心脏增大的病例明显低于A、B两组。RRF状态与透析效能呈正相关。本组患者除2例在透析治疗时即无尿,128例患者中有31例(24·2%)发生无尿,其中原发病为血管炎综合征及糖尿病肾病各占4例和7例,其无尿发生率分别占本病种的66·7%及25·9%;另20例无尿患者为肾小球肾炎或其它疾病,占此类疾病的20·6%。此外,发生无尿患者中有5例(16·1%)透析时尿量<300ml/d。结论:PD患者的残余肾仍然是清除体内代谢产物的重要途径,同时也影响血压及心血管系统并发症。     

灯盏花对自发性高血压大鼠肾脏保护作用的实验研究

目的 :观察蛋白激酶 C ( PKC)抑制剂——灯盏花对自发性高血压大鼠 ( SHR)肾脏的保护作用。方法 :将 12只 10月龄 SHR随机分为灯盏花 ( SHRD)和生理盐水 ( SHRC)组 ,均以 10 m g/ ( kg· d)腹腔内注射 ,连续8周。测定血压、心率 ,用光镜、电镜观察肾脏结构改变。图像分析仪计算肾小球间质胶原面积、含量。结果 :SHRD组肾脏组织结构均有明显改善 ,肾小球面积校正后的胶原面积 ( GCA/ GA) ,SHRD 组较 SHRC 组降低 14 .87%〔( 14 .66± 1.74 ) % vs( 17.2 2± 2 .0 1) % ,差异有显著性意义 ( P <0 .0 5 )〕。结论 :SHRD 能在降低 SHR血压的同时延缓肾小球硬化发展的作用     

beta(2)-adrenoceptors activate nitric oxide synthase in human platelets

Nitric oxide (NO), generated by platelets through stimulation of nitric oxide synthase (NOS), limits platelet adhesion and aggregation after a prothrombotic stimulus. Platelet beta-adrenoceptors (betaARs) mediate inhibition of aggregation, but no direct link has been shown between these receptors and platelet adhesion or NO production. We examined NOS activity in human platelets from the conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline, after betaAR stimulation or cAMP elevation. Basal NOS activity was 0.11+/-0.03 pmol L-citrulline/10(8) platelets. The betaAR agonist isoproterenol 1 micromol/L and the adenylyl cyclase activator forskolin 1 micromol/L each increased NOS activity, to 0.26+/-0.04 and 0.23+/-0.03 pmol L-citrulline/10(8) platelets, respectively (P<0.01 for each). Both responses were abolished by the adenylyl cyclase inhibitor SQ22536 50 micromol/L. NOS activation by isoproterenol or forskolin was not associated with a change in intracellular Ca(2+). In functional studies, isoproterenol inhibited U46619-induced platelet aggregation in a concentration-dependent manner, but this effect was not significantly diminished by NOS inhibition. In contrast, thrombin-stimulated platelet adhesion to cultured human umbilical vein endothelial cell monolayers was inhibited by isoproterenol, and this effect was abolished by NOS inhibition (1.3+/-0.2% versus 2.6+/-0.2% respectively; P<0.001). Effects of isoproterenol on NOS activity, platelet aggregation, and adhesion were mediated exclusively through beta(2)ARs, as determined by coincubation with betaAR subtype-selective antagonists. We conclude that beta(2)ARs activate platelet NOS by increasing cAMP, and that this activation is Ca(2+)-independent. beta(2)ARs may contribute to modulation of platelet aggregation and adhesion to endothelium, and our findings suggest that activation of the L-arginine/NO system mediates the effects of beta(2)ARs on adhesion but not aggregation.     

蛋白激酶C激活剂对缺氧性动脉高压大鼠离体肺动脉环反应性？…

观察缺氧性动脉高压大鼠离体肺动脉环对蛋白激酶激活剂豆蔻酸佛波酰乙酰的反应性变化。方法取缺氧２周并已经形成肺动脉高压的大鼠和正常对照组大鼠肺动脉环,观察在离体情况下对０．５μｍｏｌ／ＬＰＭＡ的最大张力反应及达到二分之一最大张力所需的时间,并描绘两肺动脉环对０．０１－１０．０μｍｏｌ／ＬＰＭＡ的浓度－反应曲线。     

吸入外源性一氧化氮对急性高原病患者内皮源性血管舒缩因子的影响

目的 了解外源性一氧化氮对急性高原病患者内皮源性血管舒缩因子的影响。方法 将47例急性高原病患者随机分为两组，常规药物组23例给予吸氧、氨茶碱、地塞米松、速尿等药物治疗；一氧化氮组24例仅吸入由海拔3658m空气平衡的0．001％一氧化氮气体，每天上午和下午各1次，每次1h。观察两组治疗前后血清一氧化氮及血浆内皮素、血栓素B2和6-酮-前列腺素F1a含量，以及临床症状的变化情况。结果 常规药物组和一氧化氮组治疗后内皮素[（78±8）和（69±5）ng／L]、血栓素B2[（87±13）和（73±8）ng／L]、内皮素／一氧化氮[（26．7±1．5）×10^3和（21．8±1．1）×10^3]、血栓素B2／6-酮-前列腺素F1a（0．84±0．36和0．58±0．11）及临床症状评分[（2．4±1．6）和（1．8±1．3）分]与治疗前内皮素[（83±8）和（84±4）ng／L]、血栓素B2[（102±16）和（103±13）ng／L]、内皮素／一氧化氮[（35．0±2．7）×10^3和（36．3±3．1）×10^3]、血栓素B2／6-酮-前列腺素F1a（1．28±0．38和1．24±0．28）及临床症状评分[（4．4±2．3）和（4．4±2．0）分]比较显著下降；治疗后一氧化氮[（2880±537）和（3167±192）μg／L]、6-酮-前列腺素F1a[（122±46）和（128±15）ng／L]与治疗前一氧化氮[（2372±144）和（2313±188）μg／L]、6-酮-前列腺素F1a[（86±28）和（86±13）ng／L]比较显著升高。一氧化氮组与常规药物组治疗后的结果比较，也表现出相同规律。结论 吸入高原现场空气平衡的外源性一氧化氮能使急性高原病患者内皮源性血管舒缩因子显著下降，对患者的康复具有积极的作用。     

抑制核因子-κB对糖尿病肾病的作用

目的　研究抑制核因子 κB(NF κB)活性对糖尿病肾病 (DN)及糖尿病大鼠肾组织纤维连接蛋白 (FN)mRNA表达的作用。方法　将纯种雄性Wistar大鼠分为 :A组为正常对照组 (1 1只 ) ,B组为糖尿病无干预组 (1 1只 ) ,C组为吡咯烷二硫基甲酸酯 (PDTC ,NF κB抑制剂 )干预组 (9只 )。饲养 1 8周后 ,以电泳迁移率变动分析技术检测肾组织NF κB活性 ,透射电镜检测肾小球基底膜厚度及系膜基质密度 (系膜基质面积 /系膜面积 ) ,逆转录PCR检测FNmRNA表达 ,收集 2 4h尿测定尿白蛋白排泄率 (UAE)。结果　NF κB活性在B组大鼠肾组织 [(1 85± 0 54)× 1 0 6 ]显著高于A组 [(0 0 7± 0 1 1 )×1 0 6 ,P <0 0 1 ] ,C组 [(0 2 5± 0 2 5)× 1 0 6 ]显著低于B组 (P <0 0 1 )。B组与A组比较 ,UAE[(2 1 8±1 98)mgvs (0 41± 0 47)mg ,P <0 0 1 ]、肾小球基底膜厚度 [(531 6± 1 0 7 6)nmvs (31 2 4± 2 5 4)nm ,P<0 0 1 ]及系膜基质密度 [(56 41± 6 78)vs (33 95± 5 2 2 ) ,P <0 0 1 ]均有显著差异 ;UAE(0 56± 0 72 )mg、肾小球基底膜厚度 (31 5 8± 2 1 4)nm及系膜基质密度 (37 97± 7 37)在C组均显著低于B组 (P值均 <0 0 1 )。FNmRNA表达在B组大鼠肾组织 (0 73± 0 2 6)显著高于A组 (0 31± 0     

Altered pressure-natriuresis in obese Zucker rats.

It has not been examined whether the pressure-natriuresis response is altered in the insulin-resistant condition. Furthermore, despite an important role of nitric oxide (NO) in modulating pressure-natriuresis, no investigations have been conducted assessing the renal interstitial NO production in insulin resistance. The present study examined whether pressure-natriuresis was altered in insulin-resistant obese Zucker rats (OZ) and assessed the cortical and medullary nitrate/nitrite (NOx) levels with the use of the renal microdialysis technique. In OZ, serum insulin/glucose ratio (23.0+/-4.0x10(-8), n=9) and blood pressure (119+/-3 mm Hg) were greater than those in lean Zucker rats (LZ; 7.0+/-1.9x10(-8) and 103+/-4 mm Hg, n=9). The pressure-natriuresis curve in OZ was shifted to higher renal perfusion pressure (RPP), and the slope was blunted compared with that in LZ (0.073+/-0.015 vs 0.217+/-0.047 microEq/min kidney weight/mm Hg, P<0.05). The basal renal NOx level was reduced in OZ (cortex, 4.032+/-0.331 micromol/L; medulla, 4. 329+/-0.515 micromol/L) compared with that in LZ (cortex, 7.315+/-1. 102 micromol/L; medulla: 7.698+/-0.964 micromol/L). Furthermore, elevating RPP increased the medullary NOx in LZ, but this pressure-induced response was lost in OZ. Four-week treatment with troglitazone, an insulin-sensitizing agent, improved hyperinsulinemia, systemic hypertension, and basal renal NOx levels (cortex, 5.639+/-0.286 micromol/L; medulla, 5.978+/-0.284 micromol/L), and partially ameliorated the pressure-natriuresis curves; the slope of pressure-natriuresis curves and elevated RPP-induced NOx, however, were not corrected. In conclusion, our study suggests that insulin resistance is closely associated with abnormal pressure-natriuresis and hypertension. These deranged renal responses to insulin resistance are most likely attributed to impaired medullary NO production within the medulla.     

Important role of the hepatic vagus nerve in glucose uptake and production by the liver

We examined the role of the hepatic vagus nerve in hepatic and peripheral glucose metabolism. To assess endogenous glucose production (EGP), hepatic uptake of first-pass glucose infused intraportally (HGU), and the metabolic clearance rate of glucose (MCR), rats were subjected to hepatic vagotomy (HV, n = 7) or sham operation (SH, n = 8), after 10 days, they were then subjected to a euglycemic-hyperinsulinemic clamp together with a portal glucose load in the 24-hour fasting state. Metabolic parameters were determined by the dual-tracer method using stable isotopes. During the experiment, [6,6-2H2]glucose was continuously infused into the peripheral vein. To maintain euglycemia (4.5 mmol/L), insulin (54 pmol x kg(-1) x min(-1)) and glucose were infused peripherally after the 90-minute tracer equilibration and 30-minute basal periods, and glucose containing 5% enriched [U-13C]glucose was infused intraportally (50 micromol x kg(-1) x min(-1)) for 120 minutes (clamp period). EGP was significantly higher in HV rats versus SH rats during the basal period (64.3 +/- 7.6 v 43.6 +/- 5.3 micromol x kg(-1) x min(-1), P < .005)) and was comparable to EGP in SH rats during the clamp period (9.3 +/- 21.5 v 1.1 +/- 11.7 micromol x kg(-1) x min(-1)). HGU was reduced in HV rats compared with SH rats during portal glucose infusion (5.9 +/- 2.4 v 10.1 +/- 3.2 micromol x kg(-1) x min(-1)). The MCR in HV rats was significantly higher than in SH rats in the basal period (11.0 +/- 2.0 v 7.9 +/- 0.8 mL x kg(-1) x min(-1), P < .01)) and was comparable to the MCR in SH rats during the clamp period (41.9 +/- 10.0 and 36.6 +/- 5.7 mL x kg(-1) x min(-1)). We conclude that innervation of the hepatic vagus nerve is important for the regulation of hepatic glucose production in the postabsorptive state and HGU in the postprandial state.     

灯盏花素对糖尿病大鼠肾小球NO／NOS的影响

成年健康雄性Wistar大鼠随机分为正常对照（NC）gi、糖尿病（DM）组、灯盏花素（EB）组,每组24只。成模2和8周后,分别测定内生肌酐清除率、尿白蛋白、肾重／体重、肾小球PKC活性、NO和NOS含量。发现灯盏花素对糖尿病肾病有保护作用,并可能通过抑制PKC的活性影响NO／NOS。     

Nitric oxide-induced inhibition of transport by thick ascending limbs from Dahl salt-sensitive rats.

The factor responsible for salt sensitivity of blood pressure in Dahl rats is unclear but presumably resides in the kidney. We tested the hypotheses that (1) thick ascending limbs of Dahl salt-sensitive rats (DS) absorb more NaCl than those of Dahl salt-resistant rats (DR) and (2) NO inhibits transport to a lesser extent in thick ascending limbs from DS. We found that basal chloride absorption (J(Cl)) by thick ascending limbs from DR was 105.8+/-10.0 pmol. mm(-1). min(-1) (n=6). Ten and 100 micromol/L spermine NONOate, an NO donor, decreased J(Cl) in DR to 65.8+/-8.5 and 46.8+/-7.0 pmol. mm(-1). min(-1), respectively. Basal J(Cl) in DS was 131.6+/-13.4 pmol. mm(-1). min(-1) (n=7). In DS, 10 and 100 micromol/L spermine NONOate decreased J(Cl) to 111.5+/-12.8 and 46.8+/-6.2 pmol. mm(-1). min(-1), respectively. No difference was observed in basal or NO-inhibited Na absorption by cortical collecting ducts or in basal or NO-inhibited oxygen consumption by inner medullary collecting ducts. Because NO acts via generation of cGMP, we measured cGMP production by thick ascending limbs from DS and DR to see whether a difference in cGMP production could account for the difference in basal or NO-inhibited transport. Basal rates of cGMP production were similar between the 2 strains. Although NO increased cGMP production by thick ascending limbs from both strains, no difference existed between DS and DR. We concluded that the reduced ability of NO to block transport in thick ascending limbs in DS may account for at least part of the salt sensitivity of blood pressure in this strain.     

肝细胞一氧化氮合酶的诱导及动力学研究

目的对内毒素和几种细胞因子诱导肝细胞一氧化氮合酶的协同效应及酶动力学参数进行研究.方法原位预灌流和段原酶循环灌流大鼠肝脏、分离肝实质细胞,观察内毒素、IFN-Y、IFN-α、TNFα、IL-lβ、IL-6及不同组合对肝细胞一氧化氮合酶活性、cGMP及NO2-+NO3的影响,分析酶动力学特征及皮质甾与酶诱导的量效关系.结果内毒素+IFN-v+TNFα+IL-lβ(IL-6)组合诱导酶表达效应最显著;酶参数分析显示Km、Vmax分别为108μmol/L和2632pmol@min1mg-1蛋白质,竞争性抑制剂L-NMMA、L-NNA作用的Ki分别为056μmolL及094μmol/L;诱导时间进程显示iNOS活性表达在9h达到峰值,但cGMP及NO2-NO3-的释放持续增加可维持至l8h;地塞米松和氢化可的松抑制肝细胞酶诱导的IC50分别为35×10-8mol/L和26×10-0mol/L.结论肝细胞诱导性一氧化氮合酶的表达依赖特异多细胞因子协同作用,这种可诱导性特征可能在内毒素血症和败血症休克发病机制中具有重要意义.