高渗盐溶液对失血性休克大鼠红细胞膜黏弹性的影响

采用微管吸吮技术,观察高渗盐溶液对失血性休克大鼠红细胞膜黏弹性的影响。Wistar大鼠随机分为0.9%NaCl(NS)、7．5％ NaCl(HS)、5％ NaCl-3.5% NaAc(HSA)三组。10min内放血使平均动脉压降至5．3kPa,维持90min。休克模型完成后,分别按4ml／kg体重静脉注入NS、HS、HSA,5min内输完。取血测定休克前、后及给药后的红细胞膜黏弹性。结果表明,休克后红细胞膜弹性模量、黏性系数较休克前显著增加。治疗后,HS组与NS组比较,弹性模量增加,黏性系数显著降低;HSA组与NS、HS组比较,弹性模量和黏性系数显著降低。结论 是HSA可显著改善失血性休克大鼠红细胞膜黏弹性。     

2.112 针刺足三里和内关穴对猫食管动力影响的实验研究

目的以往曾有报道针刺足三里穴可以改善食管蠕动和降低LES的压力,改善贲门器质性梗阻和机能性梗阻(achalasia)病人所致的吞咽困难.我们意图通过针灸对猫(动物)实验的研究,进一步了解针刺对食管动力的作用.方法本研究应用6只健康猫(2.5～3.5kg),LES压力和食管体运动经荷兰M MS压力检测系统和7导测压管检测.观察静息状态(10min)针刺中(3min捻转)滞针期(10min) 停针后(10min),并重复3次,比较针刺足三里穴位(双侧)和内关穴(双侧)对食管动力的作用 .结果 18次针刺足三里穴时有67%(12/18)LES压力增加,6只猫针刺反应率为3 3%～100%,增幅为17.5～90.8%,针刺后LES变化率平均为88.8%.针刺内关穴18次中,仅 6次LES有轻微增高,变化率为20.8%,针刺足三里穴与针刺内关穴相比差异显著(P＜0 .05).针刺上述2个不同穴位时,食管体蠕动均未见明显变化.结论针刺足三里穴对LES压力有明显增加作用.     

心肌缺血损伤小型猪模型内关穴位埋针后血管新生及成纤维细胞生长因子mRNA和蛋白的表达

背景：血管生成及成纤维细胞生长因子与心肌缺血损伤后修复关系密切,针刺内关防治心肌缺血损伤的机制是否与此有关尚不清楚。 目的：观察内关穴位埋针对心肌缺血损伤小型猪血管新生及成纤维细胞生长因子基因和蛋白表达的影响。 方法：将32只小型猪随机分为4组,采用左冠状动脉前降支结扎法建立心肌缺血模型,假手术组穿线但不结扎,内关组和膈俞组分别在造模的基础上进行内关、膈俞穴埋针治疗,模型组和假手术组不进行任何干预。 结果与结论：免疫组织化学染色显示小型猪经冠脉结扎后心肌毛细血管密度降低(P < 0.01),内关、膈俞穴埋针治疗7 d,损伤心肌组织毛细血管密度增加(P < 0.05或P < 0.01),内关组优于膈俞组(P < 0.05);Real time PCR和Western blot检测显示小型猪经冠脉结扎后心肌组织成纤维细胞生长因子mRNA和蛋白表达量显著增高(P < 0.05或P < 0.01),内关和膈俞穴位埋针治疗均可上调成纤维细胞生长因子mRNA和蛋白表达量,以内关埋针效果最明显(P < 0.05)。揭示内关、膈俞穴位埋针均可通过上调成纤维细胞生长因子mRNA和蛋白的表达,增加心肌毛细血管密度,改善缺血心肌的损伤,且内关优于膈俞。     

内关穴位埋针心肌缺血损伤小型猪血管生长功能性基因的表达谱

背景：内关针刺可上调相关血管生长因子的表达,但血管新生相关生长因子较多,针对部分因子研究有局限性。 目的：观察心肌缺血损伤小型猪血管生长功能性基因表达谱特征及内关穴位埋针的干预效应。 方法：将32只小型猪随机分为4组,模型组采用左冠状动脉前降支结扎法建立小型猪心肌缺血模型,内关组和膈俞组分别在造模基础上进行内关、膈俞穴埋针治疗,假手术组穿线不结扎。埋针7 d后取各组小型猪的缺血心肌组织进行实验。 结果与结论：应用Q Series血管生长功能基因组表达谱芯片共检测到96个与血管生成功能密切相关的基因。与模型组比较,内关组显著上调基因17个,下调基因3个,膈俞组显著上调基因14个,下调基因2个。就其基因功能分类而言,内关组、膈俞组与模型组比较差异表达基因各有其自身特点,但特异的促进因子和抑制因子、血小板衍生生长因子及受体、成纤维细胞生长因子及受体、生长因子及受体以及其他细胞生长因子,细胞因子和化学增活素、基质蛋白酶及抑制剂以及其他相关基因是各组共有的,其中以血管生长因子及受体最多。说明心肌缺血以及穴位埋针后的干预均与血管生长因子差异表达有关,但内关埋针与膈俞埋针作用不完全相同。     

低强度激光修复术对小型巴马猪退变椎间盘VEGF表达的影响

目的制备小型巴马猪椎间盘退行性病变模型,观察低强度激光对猪椎间盘血管内皮生长因子(VEGF)表达的影响。方法小型巴马猪9头,随机分为对照组(Con组),造模组(Mod组)及激光治疗组(Las组),每组3头。Con组不进行任何处理, Mod组及Las组在C形臂X光引导下利用16G针刺入猪L2-3、L3-4、L4-5、L5-6椎间盘进行破坏,Las组猪椎间盘退变模型建立1个月后,再对已处理的椎间盘进行低能量激光治疗再观察1个月,进行MR检测,治疗1个月后取椎间盘HE染色、免疫组化及Western blot检测VEGF的表达情况。结果三组在造模前、造模后1个月、治疗后1个月,Con组猪的椎间盘T2加权像呈高信号,Mod组信号强度明显下降,Las治疗组呈中、高信号影。HE染色Con组结构完整,Mod组结构遭到破坏,Las组结构较Mod组显著恢复。与Con组比较,Mod组和Las组猪椎间盘的VEGF表达均显著升高(P 0.05),但Las组VEGF表达较Mod组显著降低(P 0.05)。结论低强度激光对小型巴马猪退变的椎间盘具有一定的保护作用,与上调椎间盘组织VEGF表达相关。     

高渗盐溶液对失血性休克大鼠红细胞几何形状的影响

目的:采用微管吸吮技术,观察高渗盐溶液对失血性休克大鼠红细胞几何形状的影响。方法:Wistar大鼠随机分为0.9%NaCl(NS)、7.5%NaCl(HS)、5%NaCl-3.5%NaAc(HSA)3组。10min内放血使平均动脉压降至5.3kPa,维持90min。休克模型复制完成后,分别按4mL/kg体重静脉注入NS、HS、HSA,5min内输完。取血测定休克前、后及给药后的红细胞几何形状。结果:休克后红细胞表/体比值、球度指数无明显变化,红细胞直径较休克前下降非常显著。治疗后,HS组与NS、HSA组比较,表/体比值降低非常显著;HS组和HSA组球度指数非常显著高于NS组,HSA组球度指数非常显著低于HS组。HS组和HSA组红细胞直径非常显著低于NS组。结论:HS和HSA不利于失血性休克大鼠红细胞几何形状的改善。HSA对红细胞几何形状的不利影响低于HS。     

经皮球囊封堵冠状动脉法制备小型猪心肌梗死模型及评价

目的: 探讨球囊封堵法建立小型猪心肌梗死模型的可行性,以及骨髓间充质干细胞(MSCs)移植治疗心肌梗死疗效初探。方法: 选用小型藏猪20只,麻醉后经股动脉置入经皮腔内冠状动脉成形术(percutaneous transluminal coronary angioplasty, PTCA)球囊至左前降支中远段,完全堵闭血流90 min,行心电图、心脏超声心动图、心肌核素显像、心脏核磁共振及病理检查。随机分2组:MSCs移植组,OTW球囊将MSCs移植到梗死心肌处;生理盐水组,注入等量生理盐水。观察2组的左室射血分数(LVEF)和短轴缩短率(FS)、左室舒张末期内径(EDV)和左室收缩末期内径(ESV)的变化。结果: 20只猪均完成冠脉造影,造模成功10只,,死亡10只,成功率50%。与造模之前比, LVEF、FS显著下降(P<0.05),EDV、ESV显著延长。8周后,MSCs移植组均较移植前好转(P<0.05, P<0.01),而生理盐水组亦有所改善,但无显著差异;MSCs移植组的LVEF和FS较生理盐水组明显增加(P<0.05,P<0.01),MSCs移植组的EDV和ESV较生理盐水组明显缩少(P<0.05,P<0.01)。结论: 球囊封堵法可成功建立小型猪心肌梗死模型,并且适合行骨髓干细胞移植的研究,但须特别注意预防心室纤颤的发生。MSCs移植可明显改善小型猪梗死心肌的功能。     

法舒地尔调控巨噬细胞极化改善糖尿病小鼠心肌纤维化

目的:探讨盐酸法舒地尔(HF)对糖尿病(D)小鼠心肌纤维化及巨噬细胞极化的影响。方法:将60只C57BL/6小鼠随机分为正常组(NS组)、正常+法舒地尔组(N+HF组)、糖尿病组(D+NS组)、低剂量法舒地尔组(D+LHF组)、中剂量法舒地尔组(D+MHF组)及高剂量法舒地尔组(D+HHF组)。采用链脲佐菌素(STZ)连续腹腔注射建立1型糖尿病小鼠模型。干预8周后处死小鼠,观察法舒地尔对小鼠体重及血糖的影响;HE及Masson染色观察心脏组织形态改变,测量心肌胶原容积分数(collagen volume fraction,CVF);免疫组化观察心脏组织中巨噬细胞极化及白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)和IL-10的蛋白水平;Western blot测定心脏组织中p-MYPT1 Thr853、诱导型一氧化氮合酶(iNOS)和精氨酸酶1(Arg-1)的蛋白水平。结果:与NS组相比,D+NS组小鼠成模后体重下降,血糖升高(P0.05);与D+NS组相比,各治疗组血糖和体重差异无统计学显著性。与NS组相比,D+NS组CVF增大,M1型巨噬细胞数量增加,M2型巨噬细胞数量减少,IL-6、TNF-α、p-MYPT1 Thr853和iNOS的蛋白水平升高,IL-10和Arg-1的蛋白水平降低(P0.05);与D+NS组相比,各治疗组CVF下降,M1型巨噬细胞数量减少,M2型巨噬细胞数量增加,IL-6和TNF-α的蛋白水平降低,IL-10的蛋白水平升高;与D+NS组相比,D+MHF和D+HHF组的p-MYPT1 Thr853和iNOS的蛋白水平下降,Arg-1的蛋白水平升高(P0.05)。与NS组相比,N+HF组各检测指标差异无统计学显著性。结论:法舒地尔能改善糖尿病心肌病小鼠心肌纤维化,其可能的机制与诱导M2型巨噬细胞极化,减少M1型巨噬细胞极化和炎症反应有关。     

狗左冠状动脉结扎后左、右心室和肺循环功能的动态演变及其相互关系

用麻醉开胸狗,观察了左冠状动脉前降支(LAD)结扎后2小时内,左,右心室舒缩性能、泵功能及肺循环压力和阻力的动态变化,并分析其相互关系。结扎LAD所造成的心肌缺血范围占左心室(LV)重量的35.2±1.4%。LAD结扎后,依次出现LV舒缩性能、肺动脉压、左、右心室泵功能、LV收缩性船、右心室(RV)舒张性能和肺血管阻力的改变,而RV收缩性能则无明显变化。结果表明,较大范围的LV心肌梗塞(MI)早期,LV功能降低可直接导致RV舒张性能降低,还可直接和通过肺循环压力和阻力升高间接使RV泵功能降低。但对RV收缩性能无明显影响。因子分析提示,LV收缩性能与两心室泵功能的改变是LVMI后心功能改变的主要方面;依次为两心室舒张性能和肺循环功能的改变。     

三七总皂苷对低氧大鼠肺动脉压和肺组织p38 MAPK表达的影响

目的:探讨三七总皂苷(PNS)对低氧大鼠p38丝裂原活化蛋白激酶(p38 MAPK)表达的影响,及预防低氧性肺动脉高压(HPH)的作用和机制。方法:将30只SD大鼠随机分为3组:正常对照组、低氧组和低氧+PNS组。观察各组大鼠平均肺动脉压(mPAP)、平均颈动脉压(mCAP)和右心室/(左心室+室间隔重量)比[RV/(LV+S)],免疫组化法和RT-PCR法分别检测肺小血管壁磷酸化p38 MAPK(p-p38 MAPK)蛋白和肺组织中mRNA的含量。结果:与对照组相比,低氧组大鼠mPAP、RV/(LV+S)明显升高,肺小动脉p-p38 MAPK及肺组织p38 MAPK mRNA含量显著升高(P0.05)。低氧+PNS组mPAP、RV/(LV+S)、肺小动脉p-p38 MAPK及肺组织p38 MAPK mRNA含量明显低于低氧组(P0.05)。结论:PNS具有显著预防HPH的作用,其机制可能与其降低p38 MAPK mRNA的表达有关。     

Compliance of the interstitial space in rats I. Studies on hindlimb skeletal muscle

Interstitial compliance, defined as the ratio between changes in interstitial fluid volume (ΔIFV) and interstitial fluid pressure (ΔIFP), was determined for rat skeletal muscle. IFV was measured as the extravascular distribution space for ⁵¹Cr-EDTA, while sharpened micropipettes connected to a servo-controlled counterpressure system were used to measure IFP. The experimental protocol was designed to bring about acute (2–4 h) and chronic (24–28h) tissue over- and dehydration. During dehydration, the average compliance was 0.056 ml/g dry weight · mmHg, corresponding to 1.40 ml/100 g wet tissue mmHg, and was not significantly different in acute and chronic experiments. In hydration (acute and chronic), compliance increased several-fold when IFV increased. Even at greatly increased IFV, IFP did not rise more than 1 to 1.5 mmHg above control level. Since control IFV amounts to 10 ml/100 g wet tissue, IFV will decrease by 14% when IFP falls by 1 mmHg from this control level. Provided unchanged interstitial protein mass the dehydration will cause interstitial fluid colloid osmotic pressure to increase by somewhat more than 1 mmHg—from a control level of 9 mmHg. Furthermore, since IFP was not increased by more than 1 to 1.5 mmHg during hydration, an increase in IFP plays a minor role in edema-prevention compared to dilution and/or washout of interstitial proteins.     

Subcutaneous interstitial pressure in man and dogs exposed to heat and exercise stress

Summary Interstitial fluid pressure (IFP) was measured by the wick method in six young men. During exercise in the heat, IFP progressively decreased, and this decrease was maintained after cessation of exercise. In two men working in the same conditions after heat acclimatisation IFP became initially positive before steadily declining. In three anaesthetised dogs exposed to heat IFP also declined, but in a thermoneutral environment it rose towards atmospheric pressure. It is suggested that IFP could be used as a measure of filtration forces operating across the capillary wall. Fluid dynamics in the interstitial space of heat acclimatised man differed, however, from that of unacclimatised man and heat exposed dogs. It is postulated that these changes may be related to movement of protein from the interstitial to the plasma compartments during exercise after acclimatisation.     

Interstitial fluid pressure correlates with intravoxel incoherent motion imaging metrics in a mouse mammary carcinoma model

The effective delivery of a therapeutic drug to the core of a tumor is often impeded by physiological barriers, such as the interstitial fluid pressure (IFP). There are a number of therapies that can decrease IFP and induce tumor vascular normalization. However, a lack of a noninvasive means to measure IFP hinders the utilization of such a window of opportunity for the maximization of the treatment response. Thus, the purpose of this study was to investigate the feasibility of using intravoxel incoherent motion (IVIM) diffusion parameters as noninvasive imaging biomarkers for IFP. Mice bearing the 4T1 mammary carcinoma model were studied using diffusion‐weighted imaging (DWI), immediately followed by wick‐in‐needle IFP measurement. Voxelwise analysis was conducted with a conventional monoexponential diffusion model, as well as a biexponential model taking IVIM into account. There was no significant correlation of IFP with either the median apparent diffusion coefficient from the monoexponential model (r = 0.11, p = 0.78) or the median tissue diffusivity from the biexponential model (r = 0.30, p = 0.44). However, IFP was correlated with the median pseudo‐diffusivity (D_p) of apparent vascular voxels (r = 0.76, p = 0.02) and with the median product of the perfusion fraction and pseudo‐diffusivity (f_pD_p) of apparent vascular voxels (r = 0.77, p = 0.02). Although the effect of IVIM in tumors has been reported previously, to our knowledge, this study represents the first direct comparison of IVIM metrics with IFP, with the results supporting the feasibility of the use of IVIM DWI metrics as noninvasive biomarkers for tumor IFP. Copyright © 2011 John Wiley & Sons, Ltd.     

循经低流阻通道组织液压的初步观察

目的 测量循经低流阻通道与周围的组织液压,观察其差异及变化情况。方法 在麻醉的小型猪上,使用连续流阻测量仪测出低流阻点和非低流阻点,然后采取针中芯方法测量组织液压。结果 统计结果表明,小型猪胃经、肾经和任脉的低流阻通道平均压力均显著低于旁开的高流阻区域,其压力差分别为1.06、0.70、3.69 mmHg（1 mmHg=0．133 kPa）,总压力差为1.44 mmHg,压力梯度为1.44~2.88 mmHg/cm。在一些低流阻点上发现了与呼吸频率一致的压力波。结论 外周皮下组织中存在着指向经脉低流阻通道的压力差,可能构成组织液向经脉流动的动力。     

Reevaluation of the needle method for measuring interstitial fluid pressure.

Inserting a needle into subcutaneous spaces should allow a subatmospheric pressure to be measured if interstitial fluid pressure is truly negative as measured by the capsule and wick techniques. Previous needle measurements of interstitial fluid pressure have produced a positive value, but in most instances fluid has been injected into the tissues prior to recording of pressure. Therefore, we measured subcutaneous needle pressure in anesthetized dogs without fluid injection into the tissues. Approximately 30 min are required for an equilibrium pressure after insertion of the needle. The mean 30-min pressure was 4.6 +/- 0.5 (SE) mmHg (n equals 41). With observable edema, interstitial fluid pressures as measured with the needle were always positive. However, the needle method for continuous recording of pressure lacks rapid sensitivity to changes in tissue fluid pressures. In order to develop a needle method that would follow changes in interstitial fluid pressure, 0.5-1 mul of saline was injected into or withdrawn from the tissue. With this method, pressure plateaued in 10-20 min. This plateau pressure increased with tissue hydration and decreased with dehydration.     

Sympathectomy decreases size and invasiveness of tongue cancer in rats

The sympathetic nervous system plays a role in carcinogenesis wherein locally released sympathetic neurotransmitters affect proliferation, angiogenesis, vessel permeability, lymphocyte traffic and cytokine production. The present in vivo study was designed to investigate whether surgical sympathectomy, both unilateral and bilateral, had an effect on tumor growth, interstitial fluid pressure (IFP) and lymphatics in rat tongue cancer. We used 4-nitroquinoline-1-oxide (4-NQO) in drinking water for 19 weeks to induce tongue cancer in 20 Dark Agouti rats. After 11 weeks, one group underwent unilateral sympathectomy and another underwent bilateral sympathectomy, while the third group underwent sham surgery. By 19 weeks, tumors in the bilaterally sympathectomized (BL-SCGx) rats were significantly smaller (P<0.05), more diffuse in appearance and less invasive (P<0.05) compared with the large exophytic tumors in the sham-operated rats. The relative lymphatic area was significantly decreased (P<0.05) in tumors in the BL-SCGx rats compared with the sham group. Interestingly, the tumors in rats that underwent unilateral or bilateral sympathectomy had a significantly lower (P<0.05) IFP than those in sham rats. Lack of tyrosine hydroxylase (TH) immunoreactive nerves and few neuropeptide Y (NPY) positive fibers indicate absence of sympathetic nerve fibers in the bilateral sympathectomized group. The peritumoral lymph vessel area was correlated with the tumor size (P<0.001), depth of invasion (P<0.001), weight of rats (P<0.005) and IFP (P<0.05). In conclusion, the present study presents evidence that deprivation of sympathetic nerves decreases tumor growth in rat tongue, probably caused by decreasing IFP and lymph vessel area.     

“Artificial Lymphatic System”: A New Approach to Reduce Interstitial Hypertension and Increase Blood Flow, pH and pO2 in Solid Tumors

A mechanical drainage system, the artificial lymphatic system (ALS), consisting of a vacuum source and drain, is evaluated for its ability to aspirate the interstitial fluids responsible for the elevated interstitial fluid pressure (IFP) observed in solid tumors. IFP, pH, and pO₂ radial profiles were measured before and after aspiration using wick-in-needle (WIN) probes, needle pH and oxygen electrodes, respectively. Laser Doppler flowmetry measured temporal changes in blood flow rate (BFR) at the tumor surface during aspiration. The WIN probe and IFP profile data were analyzed using numerical simulation and distributed mathematical models, respectively. The model parameter, p _E reflecting central tumor IFP, was reduced from 15.3 to 5.7 mm Hg in neuroblastoma and from 13.3 to 12.1 mm Hg in Walker 256, respectively, following aspiration. The simulation demonstrated that spatial averaging inherent in WIN measurements reduced the calculated magnitude of the model parameter changes. IFP was significantly lower (p < 0.05), especially in regions surrounding the drain, and BFR was significantly higher (p < 0.05) following 25 and 45 min of aspiration, respectively; pH and pO₂ profiles increased following aspiration. The experimental and mathematical findings suggest that ALS aspiration may be a viable way of reducing IFP and increasing BFR, pO₂ and pH and should enhance solid tumor chemo and radiation therapy. © 2000 Biomedical Engineering Society. PAC00: 8719Tt, 8715Vv, 8719Uv, 8780-y, 8719Xx     

猫内囊组织间液经纤维束间隙向脑室的引流

目的探讨生理状态下猫内囊组织间液在纤维束间隙内的引流方向,方法将 5 μl 印度墨汁 0．4 μl／min 的速度立体定位地注射于猫内囊,在脑切面、2 mm 透明脑薄片及石蜡切片上对碳颗粒的扩散和引流途径予以观察。结果脑切面及透明后的脑薄片显示,墨汁在三个平面上均沿白质扩散;脑室外侧壁轻微黑染。光镜下,墨汁从脑内注射点沿白质纤维网向脑室方向扩散。脑室管膜下,碳颗粒成簇呈线状排列。结论猫内囊组织间液经纤维束间隙弥散到脑室管膜下区,由此可能引流入脑室。     

各向异性传导系数对实体肿瘤间质流体流动影响的二维边界元模拟

目的研究实体肿瘤组织间质各向异性传导系数对流体流动的影响。方法用图像处理方法建立具有实体肿瘤微血管形态和分布特征的二维微血管网络模型, 应用边界元方法数值计算多连通区域内组织液的流动及水力传导系数变化的影响。结果横向与纵向间质水力传导系数的不同, 对整个肿瘤内组织间质压强的分布有明显的影响; 不同函数形式分布的水力传导系数, 影响肿瘤局部区域内间质流体压强的分布。结论各向异性水力传导系数对实体肿瘤组织间质压强有明显影响, 与传导系数变化的范围和肿瘤内微血管网络的形态有关。     

Interstitial matrix and transendothelial fluxes in normal lung

Pulmonary gas exchange critically depends upon the hydration state and the thinness of the interstitial tissue layer within the alveolo-capillary barrier. In the interstitium, fluid freely moving within the fibrous extracellular matrix equilibrates with water chemically interacting with hyaluronic acid and proteoglycans, the non-fibrillar components of the matrix. The integrity of the macromolecular assembly of the tissue matrix is required in all processes involved in establishing and maintaining the adequate interstitial tissue fluid volume, by providing: (a) a stiff three dimensional fibrous scaffold, functioning as an efficient safety factor to oppose fluid filtration into the tissue and preventing tissue fluid accumulation; (b) a restrictive perivascular and interstitial sieve with respect to plasma proteins; (c) a mechanical support to initial lymphatics. Therefore, disturbances of the deposition and/or turnover of the matrix and/or of its three dimensional architecture and composition are invariably accompanied by profound changes of the steady state tissue fluid dynamics, eventually evolving towards severe lung disease.