一氧化氮合酶抑制剂对创伤性休克的干预作用

目的：评价选择性诱导型一氧化氮合酶（iNO）抑制剂氨基胍（AG）和非选择性一氧化氮合酶抑制剂L-N位硝基精氨甲酯（L-NAME）对创伤性休克的治疗效果。方法：40只Wistar大鼠制作创伤性休克动物模型。双侧股骨干砸伤后并经股动脉放血至平均动脉压（MAP）35～45mmHg（4．67～6.00kPa），维持30min，然后回输失血和等量的林格式液。随机分为休克组（10只）,AG组（根据复苏时静脉注射AG含量为10，50mm／kg。则分为AGⅠ，AGⅡ各10只），L-NAME组（10只，复苏时静脉注射LNAME10mg/kg），观察休克前后血浆NO浓度的动态变化及24h大鼠存活率。并留取肺、肝、肾、小肠组织，观察病理改变。结果：大鼠创伤性休克后，血浆NO水平明显高于休克前；AG各组动物复苏后血浆NO的水平明显降低，各脏器的病理损害亦显著减轻，存活率明显提高，AGⅡ组效果最好；L-NAME组动物复苏后血浆NO的水平也明显降低，各脏器的病理损害无明显变化，存活率无明显提高。结论：NO在创伤性休克的病理发展过程中起着重要作用，应用AG有助于创伤性休克的改善；L-NAME能降低NO的水平，但对休克的预后无明显改善。     

一氧化氮合酶抑制剂对骨关节炎的潜在治疗意义

目的探讨一氧化氮合酶(NOS)抑制剂L-N6-亚氨乙基-赖氨酸(L-NIL)和S-甲基异硫脲(SMT)对骨性关节炎(OA)软骨和滑膜代谢的影响,为NOS抑制剂的临床应用提供理论依据。方法无菌条件下,取17例OA患者关节软骨和滑膜,置入体外培养系统,随机分为(1)对照组:不加药物干预;(2)L-NIL组:加入NOS抑制剂L-NIL干预;(3)SMT组:加入iNOS抑制剂SMT干预。培养72h后,通过检测硝酸盐和亚硝酸盐的含量来观察软骨NO的释放量以及NOS的活性;原位杂交检测软骨iNOSmRNA和MMP9mRNA的表达。培养10d后,化学比色法观察软骨蛋白多糖含量和羟脯氨酸释放量的变化。结果对照组软骨和滑膜培养72h后,在其上清液中均可检测到高浓度NO和高活性NOS。其中软骨NO释放量和NOS活性明显高于滑膜NO释放量和NOS活性(P<0.05);原位杂交也检测到软骨iNOSmRNA和MMP9mRNA的高表达。L-NIL组和SMT组软骨和滑膜NO释放量较对照组明显减少,NOS活性明显降低(P<0.01);而L-NIL组和SMT组NO释放量和NOS活性之间的差异无显著性意义(P>0.05)。同时,未检测到iNOSmRNA和MMP9mRNA表达。培养10d后,L-NIL和SMT组OA软骨蛋白多糖的含量比对照组明显增加(F=86.3,P<0.01),羟脯氨酸释放量比对照组显著减少(F=38.1,P<0.01)。结论NOS抑制剂L-NIL和SMT能抑制过量NO的释放,改善软骨代谢环境     

一氧化氮合酶抑制剂对关节软骨修复的影响

目的观察一氧化氮合酶(iNOS)抑制剂S-甲基异硫脲(S-methylisothiourea,SMT)对关节软骨修复的影响,探讨NO在软骨修复过程中的作用。方法36只新西兰大白兔双侧股骨髁间关节面制成全层软骨缺损,随机分为3组:(1)对照组12只,软骨缺损区旷置;(2)rhBMP组12只,缺损区充填rhBMP纤维蛋白凝胶复合物;(3)SMT组12只,缺损区充填rhBMP纤维蛋白凝胶复合物后,皮下注射iNOS抑制剂SMT。术后16周处死动物,按组织形态学分级标准,作修复组织质量评价;天狼猩红-苦味酸染色观察修复组织内Ⅰ、Ⅱ型胶原分布;化学比色法检测NO释放量和NOS活性;35S掺入法检测蛋白多糖合成率;RT-PCR检测iNOS和MMP9mRNA的表达情况。结果术后16周,形态学评分表明,SMT组和rhBMP组在缺损区充填程度方面与对照组差异无显著性意义(F=2.32,P >0.05),在边缘修复结合度、细胞形态和缺损区结构以及软骨下骨修复等方面均优于对照组(P<0.05),其中SMT组优于rhBMP组(P<0.05)。化学比色法显示SMT组NO释放量(24.97±3.95)μmol/L和NOS活性(1.17±0.31)U/ml显著低于rhBMP组和对照组(F=21.287,F=15.932,P<0.05)。SMT组Ⅰ型胶原明显少于rhBMP组和对照组,Ⅱ型胶原多于rhBMP和对照组。SMT组35S掺入量(48276±5791.58)cpm明显高于对照组(10285±867.5)cpm和rhBMP组(37624±5     

一氧化氮合酶抑制剂对重度失血性休克的治疗效果

目的 评价选择性诱导型一氧化氮合酶（ｉＮＯＳ）抑制剂氨基胍（ＡＧ）和非选择性一氧化氮合酶抑制剂Ｌ－Ｎ－位硝基精氨甲酯（Ｌ－ＮＡＭＥ）对重度失血性休克的治疗效果。方法 ４０只大白兔按照Ｗｉｇｇｅｒｓ改良法制作失血性休克模型,经股动脉放血至ＭＡＰ３０～３５ｍｍＨｇ,维持１２０ｍｉｎ,然后回输失血和等量的林格氏液,随机分为休克组（１４只）、ＡＧ组（１４只,复苏时静脉注射ＡＧ２０ｍｇ／ｋｇ）、Ｌ－ＮＡＭＥ组（１２只,复苏时静脉注射Ｌ－ＮＡＭＥ３０ｍｇ／ｋｇ）,观察休克前后血浆内毒素、ＴＮＦα、Ｎ 度的动脉变化、２４ｈ和４８ｈ存活率,４８ｈｘ后留取肺、小肠、肝、肾组织观察病理改变。结果 动物失血性休克后,血浆内毒素、ＴＮＦα、ＮＯ水平明显高于休克前;ＡＧ组动物复苏后血浆内毒素、ＴＮＦα、ＮＯ的水平在失血性休克的病理发展过     

大鼠移植肝组织中一氧化氮合酶的表达及其抑制剂的作用

目的 观察大鼠移植肝组织中一氧化氮合酶(iNOS)的表达及iNOS抑制剂氨基胍和免疫抑制剂他克莫司(FK-506)对肝移植术后急性排斥反应的影响。方法 实验分为4组：同基因组(供、受者均为LEW大鼠)；急性排斥组(供者为BN大鼠，受者为LEW大鼠)；氨基胍组、FK506组在异基因大鼠肝移植后分别应用氨基胍和FK506。用免疫组织化学法检测各组移植肝组织中iNOS表达水平。结果 急性排斥组iNOS表达呈强阳性，与氨基胍组、FK506组、同基因组比较，差异显著。结论 在大鼠原位肝移植发生急性排斥反应时，iNOS增高程度与排斥反应的强度有明显关系。氨基胍和FK506可以抑制iNOS的表达，明显减轻移植肝组织的急性排斥反应。     

一氧化氮合酶抑制剂对延缓腰椎间盘退变的影响

目的　探讨一氧化氮合酶(NOS)抑制剂L N6 亚氨乙基 赖氨酸(L NIL)和S 甲基异硫脲(SMT)对退变腰椎间盘组织代谢的影响。方法　无菌条件下,取2 0例腰椎间盘突出症患者的椎间盘组织体外培养,分别加入1mmol/L浓度的SMT和L NIL ,培养72h后,通过检测硝酸盐和亚硝酸盐的含量来观察椎间盘NO的释放量及NOS的活性;原位杂交法检测椎间盘组织iNOSmRNA和MMP3mRNA的表达。培养10d后,化学比色法观察椎间盘蛋白多糖含量和羟脯氨酸释放量的变化。结果　L NIL组髓核和纤维环NO释放量(65 .6±4.5 ,68.8±5 .7) μmol/L和SMT组髓核和纤维环NO释放量(69.5±6.5 ,69.1±6.1) μmol/L较对照组NO释放量(10 7.9±4.4,93 .1±5 .9) μmol/L明显减少(P <0 .0 1)。L NIL组和SMT组髓核组织中蛋白多糖含量(5 1.3±9.6,48.2±8.5 )kg/L ,比对照组(3 2 .1±6.4)kg/L明显增加(P <0 .0 1) ,羟脯氨酸释放量(1.1±0 .4,1.2±0 .5 )kg/L比对照组(3 .4±0 .8)kg/L显著减少(P <0 .0 1) ;同时,原位杂交法未检测到iNOSmRNA和MMP3mRNA的表达。结论　NOS抑制剂L NIL和SMT能抑制过量NO的释放,对延缓椎间盘退变具有积极的作用     

一氧化氮合酶抑制剂对关节软骨缺损修复影响的形态学研究

目的　探讨诱导型一氧化氮合酶 (iNOS)抑制剂S 甲基异硫脲 (SMT)对关节软骨修复的影响。方法　将 2 0只新西兰大白兔双侧股骨髁关节面造成全层软骨缺损。随机分为 2组 :对照组 10例 ,缺损软骨面用纤维蛋白凝胶BMP复合物充填 ;给药组 10例 ,缺损软骨面用纤维蛋白凝胶BMP复合物充填后 ,皮下注射SMT(5mg·kg-1·12h-1)。术后 8周、16周、1年处死动物 ,按组织形态学分级标准 ,双盲法行 16周和 1年修复组织评价 ;化学比色法检测修复组织NO释放量和NOS活性。结果　形态学观察证实 ,术后 8周、16周及 1年后 ,给药组软骨缺损修复在缺损区结构、细胞形态和基质染色等评分方面优于对照组 (P <0 0 5 )。术后 16周及 1年对照组NO释放量和NOS活性明显高于给药组 (P <0 0 5 )。结论　iNOS抑制剂SMT可减少NO释放 ,降低iNOS活性 ,提高软骨修复质量。     

诱导型一氧化氮合酶抑制剂对胆管癌细胞生物学行为的影响

目的:探讨诱导型一氧化氮合酶抑制剂(i NOS)抑制剂对胆管癌细胞生物学行为的影响。方法:不同浓度i NOS抑制剂1400W孵育人胆管癌QBC939细胞24 h后,分别用硝酸还原酶法、MTT比色法检各组细胞中NO浓度与增殖情况,并计算半抑制浓度(IC_(50));根据IC_(50)值,选择合适浓度的1400W处理QBC939细胞24 h后,分别用划痕试验、Transwell小室法检测细胞迁移及侵袭情况。以上实验均以未加1400W培养基处理的QBC939细胞为空白对照。结果:与空白对照组比较,各1400W处理组QBC939细胞中NO含量及增殖率均呈浓度依赖性降低(均P0.05),IC_(50)值为51.24μmol/L;用_(50)μmol/L的1400 W处理QBC939细胞24 h后,实验组的细胞划痕愈合率(61.7%vs.92.3%)和细胞侵袭数(72.7个vs.128.0个)均较对照组明显降低(均P0.05)。结论:i NOS抑制剂1400W能抑制胆管癌细胞增殖、迁移和侵袭,其机制可能与NO下游的信号分子变化有关。     

一氧化氮合酶抑制剂对炎性刺激下软骨细胞增殖和基质代谢的影响

目的　用白细胞介素 1β(IL 1β)和脂多糖 (LPS)模拟软骨细胞和软骨的炎性环境 ,探讨一氧化氮合酶 (NOS)抑制剂对软骨细胞增殖和基质代谢的影响。方法　实验共分 5组 :对照组、IL 1β和LPS刺激组、IL 1β和LPS +S 甲基异硫脲 (SMT)组、IL 1β和LPS +L NIL组、IL 1β和LPS +L NMA组。清洗干净的软骨块和传至第二代的软骨细胞依次加入上述药物。采用MTT法和BrdU掺入法分别检测软骨细胞和软骨的增殖活性 ;化学比色法检测NO释放量、NOS活性 ;3 5S掺入法检测蛋白多糖合成率。结果　①外源性IL 1β和LPS可增加软骨细胞和软骨NO释放 [(2 0 4 5± 14 )μmol/L ,(2 0 9 8± 18) μmol/L],诱导iNOSmRNA表达 ,增加NOS活性 [(2 0 1 7± 17)U/ml,(2 98 7±2 0 )U/ml) ],抑制软骨蛋白多糖合成和软骨细胞增殖 (P <0 0 5 ) ;②不同浓度NOS抑制剂均能减少NO释放和降低NOS活性 ,并与药物剂量正相关 ;③ 1mmol/L的NOS抑制剂可显著逆转软骨细胞和软骨蛋白多糖合成抑制 (P <0 0 5 ) ,增加软骨细胞增殖活性。结论　NOS抑制剂能有效抑制炎性因子 (IL 1β和LPS)诱发的软骨代谢改变 ,对关节软骨损害具有潜在的保护作用。     

感觉神经保护延缓失神经性肌萎缩的实验研究

目的研究感觉神经延缓失神经肌萎缩的作用。方法成年雄性SD大鼠40只,随机分成两组,实验组(n=20)即感觉神经移植保护组,对照组(n=20)即纯失神经组。第一阶段:对照组仅横断肌皮神经。实验组完成近端锁骨上神经和远端肌皮神经吻合。第二阶段:第一阶段术后6个月,实验组及对照组完成胸小肌运动神经分支与肌皮神经远端的吻合。第二阶段术后4周及8周内,分别测定大鼠理毛实验、运动单位电位、肌肉湿重、肌肉HE染色、运动终板染色计数等。结果实验组术后第4及8周运动单位电位波幅明显高于对照组,电流刺激敏感度明显优于对照组。二头肌湿重恢复率、肌纤维直径、肌纤维截面积恢复率、运动终板数明显优于对照组。理毛实验于术后第2周时优势明显。结论近端感觉神经与远端运动神经端端吻合可有效延缓失神经肌肉萎缩。     

神经肌蒂移位预防失神经肌萎缩的实验研究

目的研究神经肌蒂移位对骨骼肌失神经肌萎缩的预防作用。方法选用SD大鼠48只,随机分为四组,每组12只。建立右下肢失神经胫骨前肌加腓骨长肌神经肌蒂移位为A组;右下肢失神经胫骨前肌加腓浅神经干埋植为B组;右侧腓总神经离断,胫骨前肌失神经对照为C组;正常对照为D组。每组随机均分为两批,分别于术后6周和12周进行步态分析、电生理检测、胫前肌湿重检测和肌纤维截面积检测,并进行评价。结果术后6周,A组在步态分析（神经功能指数为-47.20±12.30）、电生理检测、胫前肌湿重检测（0.3840±0.0246g）和肌纤维截面积（1040.98±120.54μm^2等各项指标都明显优于C组（分别为-114.40±14.84、0.1730±0.0191g和585.08±182.93μm^2,差异有统计学意义（P〈0.05）;胫前肌湿重、肌纤维截面积检测优于B组（分别为0.2940±0.0564g和763.92±82.68μm^2,差异有统计学意义（P〈0.05）。术后12周A组肌纤维截面积1360.10±261.45μm^2D组1544.57±266.92μm^2较差异无统计学意义（P〉0.05）,达到正常值范围;A组在步态分析（神经功能指数为-31.60±25.34）、电生理检测、肌纤维截面积方面均优于B、C两组,比较差异有统计学意义（P〈0.05）。结论神经肌蒂移位对失神经肌萎缩有预防作用,对失神经肌萎缩预防效果优于神经干埋植。     

氨哮素对失神经骨肌内胶原代谢的影响

为探讨氨哮素对人体失神经骨骨各肌内胶原代谢的影响，采用安慰剂对照的随机双盲研究法，对７１例因臂丛神经损伤而致肌皮神经功能完全丧失的患者，给予氨哮素或安慰剂６０μｇ，每天２次，治疗３个月。实验前、后均行肱二头肌活检，活检肌肉作Ⅰ型、Ⅳ型胶原的免疫组织化学染色和图像分析。结果表明，氨哮素治疗组肌内膜中Ⅰ型胶原明显低于安慰剂组，Ⅳ型胶原纤维的增生明显少于安慰剂组（Ｐ＜０．０５）。证明，氨哮素能抑制失神经骨骨各肌内胶原的增生     

INFLUENCE OF THE ENDOTHELIAL NITRIC OXIDE SYNTHASE POLYMORPHISM ON THE PROGRESSION OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE AND IgA NEPHROPATHY

Background: The reason of variability of clinical course and progression to end-stage renal failure (ESRF) of two widespread chronic nephropathies–-autosomal dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IGAN) is not clear. The endothelial dysfunction is considered in the number of factors possibly influencing the prognosis of these nephropathies. Our study tried to verify the hypothesis that endothelial nitric oxide synthase (ecNOS) gene polymorphisms in intron 4 could have some relevance to the progression of ADPKD and/or IgA nephropathy. Methods: We examined 128 Czech patients with ADPKD (62 males, 66 females) and 93 patients with IGAN (51 males, 42 females). As a control group we used 100 genetically unrelated healthy subjects (50 men, 50 women, mean age 51.2 ± 8.2). The genomic DNA was amplified by polymerase chain reaction (PCR) and the products were separated on 1.5% agarose gel and visualized by ultraviolet transillumination. We compared homozygous subjects for ecNOSb allele with homozygous and heterozygous subjects for ecNOSa allele. Results: The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 19% (19/100) and 81% (81/100) in the control group. The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes in ADPKD patients were: 26.6% (8/30) and 73.4% (22/30) in ADPKD patients with normal renal function, 30% (9/30) and 70% (21/30) in ADPKD with ESRF, 35.2% (18/51) and 64.8% (33/51) in young ADPKD patients, 60% (12/20) and 40% (8/20) in ADPKD patients with ESRF later than in 62 years. In IGAN the frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 24% (12/50) and 76% (38/50) in IgA with normal renal function and 20.9 % (9/43) and 79.1% (38/43) in IgA with ESRF. Conclusion: Both in ADPKD and IGAN groups there was no significant difference in the frequencies of ecNOS genotypes between patients with normal renal function and age matched patients with ESRF and between patients with normal renal function and control group. The frequency of ecNOS a allele was significantly higher in a number limited group ADPKD patients with ESRF later than in 62 years (Chi-square test p < 0.05). This higher frequency of a allele among ADPKD patients with later onset of ESRF could suggest the trend of positive influence of a allele in ADPKD patients.     

INFLUENCE OF THE ENDOTHELIAL NITRIC OXIDE SYNTHASE POLYMORPHISM ON THE PROGRESSION OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE AND IgA NEPHROPATHY

Background: The reason of variability of clinical course and progression to end-stage renal failure (ESRF) of two widespread chronic nephropathies—autosomal dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IGAN) is not clear. The endothelial dysfunction is considered in the number of factors possibly influencing the prognosis of these nephropathies. Our study tried to verify the hypothesis that endothelial nitric oxide synthase (ecNOS) gene polymorphisms in intron 4 could have some relevance to the progression of ADPKD and/or IgA nephropathy. Methods: We examined 128 Czech patients with ADPKD (62 males, 66 females) and 93 patients with IGAN (51 males, 42 females). As a control group, we used 100 genetically unrelated healthy subjects (50 men, 50 women, mean age 51.2 ± 8.2). The genomic DNA was amplified by polymerase chain reaction (PCR) and the products were separated on 1.5% agarose gel and visualized by ultraviolet transillumination. We compared homozygous subjects for ecNOSb allele with homozygous and heterozygous subjects for ecNOSa allele. Results: The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 19% (19/100) and 81% (81/100) in the control group. The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes in ADPKD patients were: 26.6% (8/30) and 73.4% (22/30) in ADPKD patients with normal renal function, 30% (9/30) and 70% (21/30) in ADPKD with ESRF, 35.2% (18/51) and 64.8% (33/51) in young ADPKD patients, 60% (12/20) and 40% (8/20) in ADPKD patients with ESRF later than in 62 years. In IGAN, the frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 24% (12/50) and 76% (38/50) in IgA with normal renal function and 20.9% (9/43) and 79.1% (38/43) in IgA with ESRF. Conclusion: Both in ADPKD and IGAN groups, there was no significant difference in the frequencies of ecNOS genotypes between patients with normal renal function and age matched patients with ESRF and between patients with normal renal function and control group. The frequency of ecNOSa allele was significantly higher in a number limited group ADPKD patients with ESRF later than in 62 years (Chi-square test p<0.05). This higher frequency of a allele among ADPKD patients with later onset of ESRF could suggest the trend of positive influence of a allele in ADPKD patients.     

诱导型一氧化氮合酶及一氧化氮在肝动脉结扎大鼠肝损伤中的意义及高压氧治疗作用

目的探讨大鼠肝脏及血清诱导型一氧化氮合酶、一氧化氮在肝动脉结扎损伤中的意义及高压氧的治疗作用。方法雄性SD大鼠96只,随机分成3组:对照组(手术对照,肝动脉未结扎)、肝动脉结扎组(结扎组)和肝动脉结扎 高压氧治疗组(高压氧组)。每组分为术后1 d、3 d、7 d、14 d时间点。高压治疗于术后2 h开始,吸纯氧60 m in,2/日,检测肝脏和血清中iNOS及NO水平,血清丙氨酸氨基转移酶(ALT),肝脏常规病理检查。结果结扎组肝组织iNOS、NO水平7 d达峰值,结扎组7、14 d与高压氧组及对照组相比均明显增高(P<0.01)。血清iNOS水平7 d、14 d结扎组明显高于高压氧及对照组,结扎组3 d血清NO水平达峰值,3 d、7 d、14 d均较高压氧组明显升高(P<0.05)。高压氧治疗各组血清ALT均较结扎组明显降低,病理示结扎组肝细胞浊肿明显,有坏死灶形成,高压氧治疗组肝细胞未见坏死。结论iNOS及NO参与了肝动脉结扎肝损害过程,高压氧治疗改善肝损害作用机制可能为抑制iNOS及NO。     

THE IMPACT OF CHRONIC RENAL FAILURE ON NITRIC OXIDE SYNTHASE ISOFORMS GENE EXPRESSION IN THE PENIS AND PELVIC GANGLIA OF RATS

PURPOSE: Patients with chronic renal failure experience a variety of physical and metabolic alterations. Uremia is often accompanied by erectile dysfunction (ED). Little information is available concerning the underlying pathophysiological mechanisms by which chronic renal failure can lead to erectile dysfunction. In this study, chronic renal failure was induced by 5/6 nephrectomy in a rat model. Cavernous nerve stimulation was used to measure the intracavernous pressure (ICP) rise. MATERIALS AND METHODS: Adult male Sprague-Dawley rats, aged between 10-12 weeks and weighing 200-250 gm. were divided into two groups. The first group (n = 20) served as a control (sham-operated) and underwent laparotomy with dissection of the perirenal fat around both kidneys. The second group (n = 40) were subjected to an excisional 5/6 nephrectomy (unilateral nephrectomy and contralateral upper and lower polar nephrectomy). Serum creatinine was measured 3 days post-operatively and at the end of the 12th week. Development of renal failure was considered if the animal had serum creatinine more than 120 microM/l. After 12 weeks, 10 animals per group were subjected to electric field stimulation (EFS) of the cavernous nerve with simultaneous recording of ICP-rise and systemic blood pressure. Northern and western blot analyses were used to determine the mRNA expression and protein contents of NOS isoforms (neuronal and endothelial) in the penile tissues and MPG. RESULTS: This remnant kidney model resulted in renal failure in 20 of 40 animals. The ICP-rise after cavernous nerve stimulation in the renal failure group was significantly impaired, 7.7+/-2.9 cm. H2O, as compared to control rats, 55.5+/-1.2 cm. H2O (p<0.001). The latency period after cavernous nerve stimulation was significantly increased in renal failure rats (6.9+/-0.95 sec.) in comparison to controls (2.4+/-0.25 sec.). Six of ten uremic animals had significantly lower testosterone (<1 nmol./l.) levels compared to non-uremic rats (3.6 nmol./l.) (p<0.005). Northern blot analysis revealed that renal failure rats had significantly higher levels of nNOS mRNA in the MPG and penile tissues than controls. There was no change in eNOS mRNA in either group. Western blot analysis demonstrated that eNOS and nNOS protein contents in the MPG and penile tissues of renal failure rats were significantly higher than those of controls. CONCLUSION: This report demonstrates that impairment of erection in renal failure rats, as determined by ICP-rise, was present in spite of elevated neuronal nitric oxide synthase mRNA and its protein in the MPG and penile tissues. Further studies are needed to determine whether erectile dysfunction is a result of post-translational changes, circulating inhibitory substances or other factors.     

失神经骨骼肌萎缩机制的研究进展

目的对近年失神经骨骼肌萎缩机制的研究进展作一综述。方法广泛查阅近年有关失神经骨骼肌萎缩的国内外文献,并进行综述。结果失神经骨骼肌萎缩的机制非常复杂,目前主要从组织学、细胞学和分子学的改变来研究萎缩机制。失神经骨骼肌纤维变细,排列紊乱,并有凋亡小体出现。促凋亡相关基因表达上调,抑制凋亡相关基因下调。骨骼肌卫星细胞在失神经支配后增多,但不能分化为成熟肌纤维,以致最后减少甚至耗竭。失神经支配萎缩的骨骼肌细胞中线粒体结构改变和代谢相关酶基因下调导致肌细胞代谢紊乱。结论骨骼肌纤维组织学改变,肌卫星细胞数量及分化改变,线粒体结构改变,凋亡相关基因和代谢相关基因表达发生改变均参与了失神经骨骼肌萎缩的发生。     

一氧化氮在家猪皮肤撕脱伤撕脱皮瓣坏死中的作用

为了探讨一氧氮和一氧化氮合成酶抑制剂－硝基左旋精氨酸甲基酯在撕脱皮瓣坏死中的作用，采用家猪下肢撕脱伤模型，用测量，称重以及微盘，组织化学和原位杂交的方法进行观察。结果：撕脱皮瓣早期ＮＯＳ基因表达增多。     

一氧化氮对急性胆道感染大鼠肾功能影响作用研究

目的　探讨一氧化氮（nitric oxide,NO）对实验性急性胆道感染大鼠肾功能的影响作用。方法　Wistar大鼠35只,随机分为急性胆道感染组（AC组）、急性胆道感染加左旋精氨酸组（L组）、左旋硝基精氨酸甲基酯组（N组）、单纯胆道梗阻对照组（O组）和假手术组（SO组）5组,分别测定血浆NO、BUN、Cr值和肾组织一氧化氮合成酶（NOS）活性,并行肝、肾组织病理变化观察。结果　L组NO、NOS高于其余各组（P＜0.05）,BUN、Cr低于AC组和N组（P＜0.05）,而与O组比较差异无显著性意义（P＞0.05）,肾组织病理变化较AC组轻;N组NO、NOS低于其余各组,而BUN、Cr则高于其余各组（P＜0.05）。结论　NO对急性胆道感染72小时大鼠的肾功能有保护作用,其作用机理可能与其舒张肾血管,增加血液灌流量等作用有关。     

CASTRATION INDUCES ACUTE VASOCONSTRICTION OF BLOOD VESSELS IN THE RAT PROSTATE CONCOMITANT WITH A REDUCTION OF PROSTATIC NITRIC OXIDE SYNTHASE ACTIVITY

PURPOSE: Previous studies demonstrating a rapid and drastic reduction of blood flow to the rat prostate gland resulting from castration caused us to consider the influence of castration on the state of vascular constriction and on the activity of the vascular tone-regulating factors (nitric oxide synthase and cyclic GMP) in the rat prostate. MATERIALS AND METHODS: Sections of ventral prostate glands obtained from intact and castrated rats were analyzed for the mean areas within smooth muscle-coated blood vessels using a computerized microscopic image analysis system. Nitric oxide synthase (NOS) levels were measured in prostatic extracts from unoperated or castrated rats using an enzyme assay system that measures conversion of 3H-L-arginine to citruline. Cyclic GMP levels were measured in prostatic extracts from unoperated or castrated rats using a competitive radioimmunoassay system. RESULTS: The mean area within ventral prostate smooth muscle-coated blood vessels was reduced 39% at 24 hours after castration (p = 0.039) and 47.7% at 48 hours after castration (p = 0.039). NOS activity measured in prostatic extracts was reduced 38% at 24 hours (p = 0.0012) and 51.6% at 36 hours after castration (p = 0.0001) compared with the control group of noncastrated rats. Finally, prostatic cGMP levels were reduced 55.8% (p = 0.0018) at 36 hours after castration when compared with controls rats. CONCLUSION: Within 24 hours after castration, the lumenal areas of smooth muscle-coated blood vessels in the rat prostate gland were found to be significantly reduced. This vasoconstriction was associated with a significant reduction of prostatic NOS activity as well as a reduction in the prostatic levels of the NOS co-factor, cGMP. Thus, acute vasoconstriction is a prominent early event associated with rat prostate regression in response to castration and likely contributes to the regression of the tissue.