卵巢切除对鼠及异常应力鼠骨密度影响的比较研究

目的：探讨卵巢切除雌激素缺乏时鼠及异常应力鼠不同部位骨密度的变化规律。材料与方法：３个月龄ＳＤ雌性大鼠６４只，双侧卵巢切除（ＯＶＸ）及行假手术（Ｓｈａｍ－Ｏ）；于术后第１、３、５、７个月各处死８只动物，切取Ｌ１～Ｌ２椎体节段、股骨及胫骨，进行ＢＭＤ（骨矿密度）检测；新生２４～７２小时雌性ＳＤ鼠４８只，建立双后肢大鼠模型，椎体、股骨及胫骨均承受较高的应力。３月龄时再同法分组，术后第２、５、７个月时分别处死动物取上述部位进行ＢＭＤ检测。结果：ＯＶＸ后第１个月椎体ＢＭＤ明显骨丢失（Ｐ＜０．０１），股骨丢失较为缓慢，７个月时方呈现差异（Ｐ＜０．０５）。松质骨区丢失时间提前（Ｐ＜０．０５）。胫骨１个月ＢＭＤ即有差异性（Ｐ＜０．０５），松质骨区则呈持续丢失。结论：鼠ＯＶＸ后ＢＭＤ的丢失速度为腰椎＞胫骨＞股骨；腰椎体＞胫骨上段＞股骨上段。双后肢大鼠组亦呈现同样变化，但腰椎、股骨及胫骨上的应力增加，ＢＭＤ的丢失较缓慢。     

一氧化氮对精子的调节作用及影响

一氧化氮 (NO)是一种不稳定的小分子有害气体 ,又是一种生物活性物质 ,参与了多种疾病的病理生理过程。NO在体内由L 精氨酸在一氧化氮合酶的作用下生成。它分布于睾丸、附睾及输精管等组织中 ,也分布于精子的顶体和尾部 ,对生精过程 ,精子活力、活率 ,受精能力以及精子脂质过氧化反应等具有重要的影响和双向调节作用。低浓度NO有益于增加精子活力、活率 ,降低精子脂质过氧化反应 ,提高精子的受精能力 ;高浓度NO对精子具有损伤作用 ,使精子活力、活率下降 ,脂质过氧化反应加强。本文简要介绍了NO在体内的产生机制 ,并着重概述了NO对精子的调节作用及影响。     

一氧化氮在过量氟对大鼠胫骨发育损伤中的作用

目的探讨一氧化氮(NO)在氟骨症发病学中的作用.方法健康SD大鼠分为对照组(饮蒸馏水)、低剂量过量氟组(饮水含氟50mg.L-1)、高剂量过量氟组(饮水含氟100mg.L-1),分别于实验后10周和20周测定大鼠血清游离氟和NO含量、骨氟含量及胫骨纵径、横径,观察胫骨骺板软骨组织细胞学变化.结果随摄氟量的增加及染氟时间的延长,大鼠血清游离氟、NO含量和骨氟含量增加,胫骨纵径、横径减短,胫骨骺板软骨出现明显病理变化;实验大鼠血清NO含量与血清游离氟和骨氟含量及骺板软骨损伤程度呈显著正相关,和胫骨纵径横径呈显著负相关.结论NO很可能在氟骨症早期骨软骨损伤中起一定的介导作用.     

抑制一氧化氮生物合成对门脉高压鼠血流动力学的影响

研究一氧化氮(NO)在门脉高压高血流动力学中的作用。方法:用SD大鼠制备肝内型(IHPH)、肝前型门脉高压(PHPH)和门腔分流(PCS)3组模型,并以正常鼠作为对照组。每一组实验动物再分成3个亚组:NO生物合成抑制剂L-NMMA组、L-NMMA NO生物合成底物L-精氨酸组以及生理盐水安慰组。血流动力学研究用放射性微球注射技术。结果:IHPH、PHPH和PCS鼠均具有心输出量和内脏血流量增加,平均动脉压、周围血管总阻力和内脏血管阻力降低等高血流动力学特征。L-NMMA能逆转门脉高压鼠和门腔分流鼠的高血流动力学状态,使之恢复至正常鼠的基础水平,但并未达到正常鼠用L-NMMA后的水平。如先给予L-精氨酸,则使L-NMMA对门脉高压鼠和门腔分流鼠的心血管作用消失。结论:门静脉高压症中NO过多产生是高动力循环重要的、但并不是唯一的介质。     

一氧化氮在肿瘤生长转移中的作用

目的 探讨一氧化氮(NO)在肿瘤生长、转移中的作用。方法 对近年来有关文献加以综述。结果 NO在肿瘤生长转移中具有双重作用，一方面NO通过干扰肿瘤细胞代谢，引起DNA损伤，形成高毒性的羟自由基，诱导肿瘤细胞凋亡，介导巨噬细胞和内皮细胞的杀瘤作用，发挥其抗肿瘤的作用；另一方面NO通过调节细胞增殖相关基因的表达，可诱导肿瘤血管形成，而具有促肿瘤生长作用。结论 选择性阻断或诱导NO的合成，使其发挥抗肿瘤作用，将为肿瘤的治疗提供新的思路和方法。     

NO对前列腺及阴茎勃起功能的调节作用

一氧化氮是一种不稳定的低分子有害气体 ,同时它又是一种生物活性物质 ,参与了多种疾病的病理生理过程。一氧化氮在体内由L 精氨酸在一氧化氮合成酶的作用下生成 ,作为一种非肾上腺能非胆碱能神经递质 ,对动物和人的生殖泌尿器官平滑肌张力起着重要的调节作用。本文简要介绍一氧化氮在体内的产生机制和分布 ,并着重概述一氧化氮对平滑肌舒张调节作用机理 ,及其在非手术治疗前列腺增生导致下尿路梗阻及改善阴茎勃起功能障碍方面的临床应用。     

一氧化氮合成酶在骨关节炎关节软骨及骨刺中的表达

目的与方法：近年来，一氧化氮在骨科领域广泛的生物学作用，引起骨科界普遍重视。本文用组化及免疫组化方法研究骨性关节软骨及骨刺中诱导型一氧化氮合成酶的表达。结果发现：一氧化氮合成酶在极早期软骨损伤中表达，定位于关节软骨表层细胞的胞浆内；在骨性关节炎关节软骨中，全层表达，以软骨细胞团表达明显，在骨刺中，表达丰富，以骨膜中软骨祖细胞层，软骨细胞团（尤其是肥大样改变的软骨细胞）、破骨细胞及成骨细胞表达明显。     

大鼠骨质疏松模型血清中一氧化氮和IL—6水平及意义

目的：测定骨质疏松模型大鼠血清中一氧化氮（NO）和IL－6水平，探讨其意义。方法：8月龄成年雌性SD大鼠随机分假手术对照组和去卵巢骨质 疏松模型组，术后第12周测量全身骨密度后处死，取血清用硝酸还原酶法测定NO水平，放免法测定IL－6和雌激素水平，结果：去卵巢骨质疏松模型组大鼠与假手术对照组相比，骨密度下降，胫骨骨小梁宽度变窄，间距变宽，小梁占视野面积比降低，血清中雌激素和NO含量显著下降，IL－6含量明显升高，大鼠骨密度与血清中雌激素和NO含量正相关，与IL－6含量负相关，结论：大鼠骨质疏松模型血清中NO水平降低，IL－6水平升高，NO和IL－6在骨质疏松的发生发展中起重要作用。     

衰老对大鼠阴茎海绵体NOSⅠ的表达和NOS活性的影响

目的 :探讨衰老对大鼠阴茎海绵体一氧化氮合酶Ⅰ (NOSⅠ)mRNA、蛋白的表达和NOS活性的影响。　方法 :30只雄性SD大鼠按不同月龄分为成年组、老年组和衰老组 ,应用Western印迹、RT PCR方法分别检测不同年龄组阴茎海绵体NOSⅠ蛋白及mRNA的表达 ;用紫外分光光度计测定不同年龄组阴茎海绵体NOS的活性。　结果 :成年组NOSⅠ 蛋白的表达量最高 ,老年组和衰老组显著降低 ,分别为成年组的 75 .6 %和 6 1.2 % ;NOSⅠmRNA的表达与蛋白表达的变化一致 ;老年组NOS活性与成年组差异无显著性 (P >0 .0 5 ) ,衰老组NOS活性明显降低 ,是成年组的70 .4 % ,并且差异非常显著 (P <0 .0 1)。　结论 :衰老引起NOSⅠ 蛋白及mRNA的表达降低和NOS活性的显著降低 ,可能是老年性阴茎勃起功能障碍的主要机制之一。     

一氧化氮在神经根性疼痛中的作用

目的：探索一氧化氮(NO)在髓核突出所致的神经根性疼痛中的作用。方法：取大鼠自体尾椎髓核无压迫下放置在L4和L5神经根表面，分别在术后3d及1、2、3、4周时观察大鼠后足机械刺激和热刺激敏感性的变化，并用免疫组化方法对移植髓核中的一氧化氮合酶(NOS)进行检测．探索NO在疼痛中的作用：结果：在无明显机械压迫情况下，大鼠腰神经根上放置自体髓核可产生痛觉过敏，移植髓核组织中NOS染色阳性一结论：髓核自身是引起腰腿痛的重要原因，NO可能参与疼痛的产生.     

Histomorphometric Evaluation of the Effects of Ovariectomy on Bone Turnover in Rat Caudal Vertebrae

The purpose of this study was to learn whether caudal vertebrae can be used to evaluate the effects of ovariectomy (OVX) in rats. Seven-month-old female Wistar rats were divided into two groups: the OVX group and the untreated control group. All rats were killed at 8 weeks and their 4th lumbar (L4), 1st caudal (C1), 3rd caudal (C3), and 5th caudal (C5) vertebrae were processed undecalcified and sectioned with Villanueva bone stain for quantitative bone histomorphometry. Both length of vertebral bodies and the cancellous tissue area in C1 were similar in size to L4 but significantly bigger than C3 and C5. Within the groups, cancellous bone volume (BV/TV) and trabecular thickness in both groups gradually increased in caudal vertebrae in relation to the distal direction. Between the groups, OVX rats exhibited a significantly lower BV/TV relative to control rats at L4 and C1, however, no significant difference were seen at C3 and C5. Bone formation-related parameters such as osteoid and mineralizing surface, and eroded surface were higher in the OVX group than in the control group in caudal as well as in lumbar vertebrae. By quantitative analysis of bone marrow composition, yellow marrow volume in C3 and C5 was significantly higher than that in L4 and C1, in both groups. Our results suggest that C1 is similar to L4 in size, bone turnover, and bone marrow composition. However, further experiments are needed to evaluate the possibility that C1 vertebra could be used as an alternative site for histomorphometric evaluation of bone changes in OVX rats. Received: 12 August 1997 / Accepted: 11 May 1998     

乌拉地尔和一氧化氮对急性缺氧犬肺循环的作用

目的 :对比观察乌拉地尔 (URA)和一氧化氮 (NO)对肺循环和体循环的影响及作用的强弱。方法 :健康杂种犬 8只 ,先观察静注URA 1mg/kg后 1～ 3 0分钟血流动力学的变化 ,然后使FIO2 降至 0 12 ,按随机顺序进行两组实验。组 1静注URA 1mg/kg ,5分钟后再吸入 90× 10 -6 容积的NO ;组 2先吸入 90× 10 -6 容积的NO ,再静注URA1mg/kg ,观察用药后血流动力学变化。结果 :静注乌拉地尔可同时降低正常犬体循环和肺循环的阻力及压力 (P <0 0 5 ) ,作用约持续 10分钟。组 1静注URA可明显降低缺氧犬MAP、SVR(P <0 0 5 ) ,再吸入NO后可再降低MPAP、PVR和SVR(P <0 0 5 ) ;组 2吸入NO后缺氧犬的PVR显著降低 (P <0 0 5 ) ,再静注URA后 ,MPAP、MAP及SVR又明显下降 (P <0 0 5 )。结论 :在急性缺氧犬模型上 ,URA静注后的扩血管作用以体循环为主。     

异丙酚和哌氟合剂辅助连硬外阻滞下行胆囊切除术血浆内皮素和一氧化氮浓度变化

目的 :观察异丙酚和哌氟合剂作为硬膜外辅助用药的临床效果及其对术中血浆内皮素 (ET)和一氧化氮(NO)水平的影响。方法 :2 1例择期胆囊切除病人随机分为两组。麻醉完善后 ,Ⅰ组用微泵输注异丙酚 2mg·kg-1·h-1;Ⅱ组给于哌替啶 5 0mg ,氟哌啶 2 5mg静注。于麻醉前、麻醉后、牵拉胆囊及术终抽静脉血测定NO和ET的含量。结果 :麻醉后两组病人BP、ET值均明显下降 ,NO值升高 ;牵拉胆囊时HR、BP、NO和ET均下降 ;Ⅰ组“胆 心反射”发生率低于Ⅱ组。结论 :麻醉后BP下降有神经及体液因素参与。牵拉胆囊时的BP下降可能系以神经调节因素占主导。小剂量异丙酚仍不能完全消除内脏牵拉反应 ,但可提供一定的心肌保护作用。     

Correlations Between Trabecular Bone Score, Measured Using Anteroposterior Dual-Energy X-Ray Absorptiometry Acquisition, and 3-Dimensional Parameters of Bone Microarchitecture: An Experimental Study on Human Cadaver Vertebrae

Developing a novel technique for the efficient, noninvasive clinical evaluation of bone microarchitecture remains both crucial and challenging. The trabecular bone score (TBS) is a new gray-level texture measurement that is applicable to dual-energy X-ray absorptiometry (DXA) images. Significant correlations between TBS and standard 3-dimensional (3D) parameters of bone microarchitecture have been obtained using a numerical simulation approach. The main objective of this study was to empirically evaluate such correlations in anteroposterior spine DXA images. Thirty dried human cadaver vertebrae were evaluated. Micro-computed tomography acquisitions of the bone pieces were obtained at an isotropic resolution of 93 μm. Standard parameters of bone microarchitecture were evaluated in a defined region within the vertebral body, excluding cortical bone. The bone pieces were measured on a Prodigy DXA system (GE Medical-Lunar, Madison, WI), using a custom-made positioning device and experimental setup. Significant correlations were detected between TBS and 3D parameters of bone microarchitecture, mostly independent of any correlation between TBS and bone mineral density (BMD). The greatest correlation was between TBS and connectivity density, with TBS explaining roughly 67.2% of the variance. Based on multivariate linear regression modeling, we have established a model to allow for the interpretation of the relationship between TBS and 3D bone microarchitecture parameters. This model indicates that TBS adds greater value and power of differentiation between samples with similar BMDs but different bone microarchitectures. It has been shown that it is possible to estimate bone microarchitecture status derived from DXA imaging using TBS.     

Involvement of the Hippocampus and Neuronal Nitric Oxide Synapse in the Gastric Electrical Stimulation Therapy for Obesity

Background  Gastric electrical stimulation (GES) has been introduced for treating obesity. However, possible central mechanisms remain to be revealed. Hippocampus has been shown to be involved in the regulation of gastrointestinal functions. Changes in hypothalamic neuronal nitric oxide synthase (nNOS) have been observed in genetically obese rodents. The aim of this study was to investigate the involvement of nNOS with GES in the rodent hippocampus. Methods  The effect of GES on gastric distension (GD) neurons was investigated using four different sets of parameters (GES-A, pulse train of standard parameters; GES-B, reduced on time; GES-C, increased pulse width, and GES-D: reduced pulse frequency), and the expression of nNOS in hippocampus was observed by fluoimmunohistochemistry staining. Results  CA1 region neurons (90.8%) responded to GD, 50.6% of which showed excitation (GD-E neurons) and 49.4% showed inhibition (GD-I neurons). Most of GD-responsive neurons (63.3%) were excited with GES. The response to GES was associated with stimulation strength, pulse width and frequency. GD-E neurons (62.5%, 76.9%, 100%, and 62.3%) and GD-I (63.6%, 47.1%, 85.7% and 50.0%) showed excitatory responses to GES-A, GES-B, GES-C, and GES-D, respectively (P < 0.05, GES-C vs. others). nNOS immunoreactive (nNOS-IR) positive neurons were observed in hippocampus CA1, CA2-3 regions and the dentate gyrus. The expression of nNOS-IR positive neurons was significantly decreased in CA1 and CA2-3 region (P < 0.05) after GES (para-C) for 2 h. Conclusions  Excitation of GD-responsive neurons and reduced expression of nNOS in the hippocampus are indicative of the central effect of GES. L. Xu and X. Sun contributed equally to this work.     

Effects of Promethazine on Bone Mass and on Bone Remodeling in Ovariectomized Rats: A Morphometric, Densitometric, and Histomorphometric Experimental Study

The effect of promethazine on bone is debated. We studied the effect of promethazine on bone and the mechanism of action involved by densitometric and histomorphometric measurements in female Wistar rats (100 days old, mean weight 25 ± 20 g). A control group of 15 rats was not manipulated. An experimental group of 15 rats were ovariectomized (OVX) at 100 days of life and fed a diet supplemented with 4.8 mg/kg promethazine hydrochloride (OVX + Prom). The group that underwent OVX and a group of 15 rats that underwent sham ovariectomy (Sham-OVX) were not treated with promethazine. After 30 days, all the rats were killed. Their femur and 5th lumbar vertebra were dissected and cleaned of soft tissue. Femoral length and vertebral height were measured with a caliper and bones were weighed on a precision balance. The bone mineral content (BMC) and bone mineral density (BMD) of the whole right femurs and 5th lumbar vertebras were measured by dual-energy X-ray absorptiometry (DXA). Trabecular bone volume (Cn-BV-TV%), trabecular number (Tb-N mm⁻¹), trabecular thickness (Tb-Th μm), and trabecular separation (Tb-Sp μm) were measured in the femurs by histomorphometric study of nondecalcified bone. Our results showed that promethazine significantly inhibited postovariectomy loss of bone mass (P < 0.0001) by significantly reducing bone resorption, as shown by the smaller trabecular spaces observed in the treated OVX rats (P < 0.0001). Received: 1 June 1998 / Accepted: 17 February 1999     

Osteoblast Gene Expression in Rat Long Bones: Effects of Ovariectomy and Dihydrotestosterone on mRNA Levels

The steroid sex hormones exert major effects on bone formation although the molecular events associated with their activity remain unclear. We have investigated the effects of ovariectomy and dihydrotestosterone (DHT) administration to both sham-operated and ovariectomized (ovx) rats on the bone mRNA levels of osteoblast genes. Rats were randomly allocated to either sham or ovariectomy operations and were administered either vehicle or 40 mg/kg body weight DHT by silastic tube implants at the time of operation for 8 weeks, at which time they were killed and total RNA was extracted from the long bones. Northern blot analysis indicated that the mRNA levels of the bone cell genes α1(I) collagen, alkaline phosphatase, osteocalcin, and osteopontin were markedly increased in ovx rats between 6- and 30-fold. DHT administration to ovary-intact, estrogen-sufficient rats increased the mRNA levels of α1(I) collagen, alkaline phosphatase, osteopontin, and osteocalcin between 3- and 9-fold. In contrast, DHT did not alter levels of these mRNA species in ovx rats. The data demonstrate that estrogen deficiency increased mRNA levels of genes expressed during osteoblast development and suggest an interplay between estrogen and androgen action in regulating the expression of a number of bone cell genes. Received: 20 May 1999 / Accepted: 21 January 2000     

碱性成纤维细胞生长因子对牵张性脊髓损伤后一氧化氮合酶活性的影响

目的观察碱性成纤维细胞生长因子(bFGF)对牵张性脊髓损伤后一氧化氮合酶(NOS)活性的影响,探讨其对脊髓损伤的保护作用。方法大鼠脊髓T13~L2经牵张损伤,皮层体感诱发电位监测P1-N1波幅下降至术前波幅70%后,于损伤平面以下经蛛网膜下腔置细导管,治疗组分别于术后即刻0·5、1、2、3、4h经细导管注入bFGF溶液20μl(含bFGF20μg),对照组在相同时间注入等量生理盐水,采用放射强度测定法测定一氧化氮合酶(NOS)含量。结果正常组NOS活性为3·92±1·31,脊髓损伤后各时相点生理盐水组较正常组NOS活性显著增加,而bFGF治疗组NOS活性明显下降,与生理盐水组比较差异有显著性意义(P<0·01)。结论bFGF能够抑制脊髓损伤后NOS的活性,减轻脊髓继发性损害,从而保护脊髓组织。     

去神经支配对青春期大鼠前列腺的影响及神经元型一氧化氮合酶的表达和意义

目的:探讨去神经对青春期大鼠前列腺生长发育的影响及神经元型一氧化氮合酶(nNOS)在其中可能的作用。方法:20只SD雄性大鼠随机分为假手术组(A组)及手术组(B组),采用显微外科技术建立去盆神经节模型,以假手术组为对照组。5周后取前列腺腹侧叶观察其形态结构的变化,并检测前列腺组织细胞凋亡及nNOS的表达。结果:B组大鼠去神经侧前列腺腹侧叶湿重比A组减少了30.8%(P<0.01),腺体明显减少,细胞高度减低,腺泡萎缩,细胞凋亡指数显著增加(P<0.01),nNOS表达下降(P<0.01)。结论:去神经支配引起前列腺组织细胞凋亡,使青春期大鼠前列腺生长发育受阻,nNOS可能在其中发挥重要的作用。     

The Effects of Nitric Oxide Supplementation and Inhibition on Bacterial Translocation in Bile Duct Ligated Rats

Obstructive jaundice promotes bacterial translocation from the gut, but the role of nitric oxide is controversial in this process. We studied the effects of nitric oxide synthase substrate, L-arginine, and nitric oxide synthase inhibitor, NG-nitro-¿-arginine methyl ester, on bacterial translocation in bile duct ligated rats. The animals were randomized into five groups; control, sham, common bile duct ligation alone, nitric oxide inhibition, and nitric oxide supplementation. Obstructive jaundice was performed with common bile duct ligation. ¿-arginine or NG-nitro-¿-arginine methyl ester was injected once daily for 14 days. Blood bilirubin level, liver histology, and bacterial translocation to the mesenteric lymph nodes as well as to the liver were assessed. The ¿-arginine supplemented group had the lowest bacterial translocation rate, but the most prominent hepatic fibrosis. Nitric oxide inhibition increased bacterial translocation to the mesenteric lymph nodes. Therefore, the administration of nitric oxide donor or inhibitor acts as a significant regulatory factor for bacterial translocation in obstructive jaundice.