急性肺栓塞大鼠肺表面活性物质的变化

目的探讨急性肺栓塞大鼠肺表面活性物质的变化情况。方法32只雄性SD大鼠以随机数字表法分为对照组、栓塞24h组、栓塞1周组、栓塞2周组,每组8只;以明胶海绵溶液经大鼠颈静脉注入制备大鼠肺栓塞模型,经右心导管测定肺动脉压、心率、呼吸频率,并行动脉血气分析。上述4组大鼠分别于肺动脉栓塞后2周、24h、1周、2周时处死,取肺组织制备病理切片,HE染色光镜下观察肺组织病理变化;逆转录聚合酶链反应、Western-blot法测定肺表面活性物质相关蛋白A(SPA)mRNA及蛋白水平。结果对照组、栓塞24h组、栓塞1周组、栓塞2周组大鼠肺动脉压平均值分别为(14.2±4.1)、(26.1±7.5)、(26.1±6.8)、(29.0±8.2)mm Hg(1mm Hg=0.133kPa),肺栓塞后大鼠肺动脉压升高(F值为3.09,P<0.05);心率分别为(415±15)、(451±35)、(463±29)、(446±14)次/min(F值为2.24,P<0.05);动脉血氧分压分别为(94.1±8.8)、(80.5±5.8)、(80.4±13.8)、(73.4±14.3)mm Hg(F值为1.25,P<0.05)。实验大鼠肺组织病理切片光镜检查,栓塞24h组可见肺组织多个血管腔有明胶海绵栓塞,栓塞1周组栓子部分溶解,栓塞2周组栓子基本溶解。大鼠肺栓塞后2周内肺组织SPA mRNA及蛋白水平显著下降,对照组、栓塞24h组、栓塞1周组、栓塞2周组肺组织SPA mRNA水平分别为1.43±0.51、0.83±0.33、0.91±0.33、0.87±0.35(F值为2.92,P<0.05);蛋白水平分别为1.00±0.00、0.44±0.18、0.44±0.33、0.52±0.32(F值为3.49,P<0.05)。结论大鼠急性肺栓塞后SPA水平显著降低,这可能与急性肺栓塞大鼠动脉低氧血症的发生有关。     

急性肺栓塞大鼠血清血管紧张素转换酶1的变化

目的探讨急性肺栓塞大鼠血清血管紧张素转换酶1的变化。方法雄性SD大鼠24只,随机分为对照组,栓塞后24 h组,栓塞后1周组,每组8只;以明胶海绵溶液经颈静脉注入制备大鼠肺栓塞模型,对照组注入同等体积生理盐水。3组大鼠分别于1周(对照组)、栓塞后24 h、栓塞后1周时处死。经右心导管测定肺动脉压、心率、呼吸频率,取动脉血行动脉血气分析及血清血管紧张素转换酶1活性测定;取肺组织制备病理切片,HE染色光镜下观察肺动脉栓塞情况。结果对照组,栓塞24 h组,栓塞1周组大鼠肺动脉平均压分别为(14.2±4.1)mm Hg(1 mm Hg=0.133 kPa)(、26.1±7.5)mm Hg(、26.1±6.8)mm Hg(P<0.05);动脉血氧分压分别为(94.1±8.8)mm Hg(、80.5±5.8)mm Hg(、80.4±13.8)mm Hg(P<0.05);3组大鼠血清血管紧张素转换酶1分别为(30.5±7.2)U/L(、53.5±15.9)U/L(、45.8±17.4)U/L(P<0.05)。光镜下观察,栓塞后24 h组肺组织切片均可见多个肺动脉管腔内海绵明胶栓塞,有继发红血栓形成,肺组织充血、水肿、炎性细胞浸润;栓塞后1周组大鼠部分肺动脉管腔内海绵明胶溶解。结论急性肺栓塞大鼠肺动脉压升高的同时,血清血管紧张素转换酶1明显升高,其程度可能与肺血管床阻塞的范围或程度有关。     

急性肺血栓栓塞症犬模型的建立

目的通过股静脉注入自体血栓,建立急性肺血栓栓塞症犬模型。方法选择杂种犬22只,由股静脉注入条形自体血栓,制成肺血栓栓塞症模型。监测注栓前、注栓后、造模后2h、造模后3h的血流动力学,检测平均肺动脉压(mPAP)、肺血管阻力(PVR)、心输出量(CO);行肺动脉造影,并使用改良Miller指数(MMI)进行量化评分。结果注栓后mPAP、PVR较注栓前明显升高[(26.01±6.34)mm Hg vs(15.62±2.30)mm Hg,1mm Hg=0.133kPa;(695.30±238.68)dyn/(s·cm5)vs(281.24±93.39)dyn/(s·cm5),1dyn=10-5 N,P0.01)],CO较注栓前明显降低[(2.25±0.38)L/min vs(2.96±0.97)L/min,P0.01)]。造模后2h和3h血流动力学指标与注栓后比较,差异无统计学意义(P0.05)。注栓后MMI升至(17.23±6.47)分,与mPAP呈正相关(r=0.723,P0.01)。结论 40ml自体血体外形成血凝块经股静脉注入,能模拟急性肺血栓栓塞症血流动力学、影像学和病理学变化,是良好的急性肺血栓栓塞症犬模型。     

两种不同方式复制大面积肺栓塞动物模型的比较

目的 比较自制可脱落球囊和自体血凝块行大面积肺动脉栓塞动物模型的异同.方法 健康绵羊18例,随机分为3组:血栓栓塞组(简称血栓组)、球囊栓塞组(简称球囊组)和空白对照组.所有动物均经全麻下监测有创肺动脉压、中心静脉压及外周动脉压.使用12 F薄壁指引导管置于右肺动脉,将自制可脱落球囊或自体血凝块经导管引入,建立肺栓塞动物模型.分别于栓塞术前、肺栓塞模型建立后0.5 h、1 h、2 h、4 h、6 h及8 h监测平均动脉压(MAP)、平均肺动脉压(MPAP)、心率、呼吸频率及外周血氧饱和度(SaO2),动脉血氧分压(PaO2)和动脉血二氧化碳分压(PaCO2).结果 2组建立大面积肺栓塞模型的绵羊均在注入自体血栓或球囊阻塞后经肺动脉造影证实为右侧肺栓塞.实验动物均存活8 h以上.动物模型建立后0.5 h～2 h出现心率、呼吸频率加快,SaO2及PaO2下降,肺动脉压增高,与空白对照组比较差异有统计学意义,但2种栓塞方法间对照差异无统计学意义.2 h后逐渐稳定,球囊组呼吸指标缓慢回升,血栓组则稳定于较低水平,球囊组与血栓组对照有统计学差异.结论 球囊栓塞较好的模拟肺栓塞的机械作用,血凝块较好的模拟血栓中活性物质的影响,可根据实验目的的不同而选择不同的模型复制方式.     

犬肺血栓栓塞后不同时间的血气、血液动力学及血栓的病理变化

目的建立犬肺血栓栓塞症(PTE)模型;观察栓塞后不同时间犬动脉血气、血液动力学、影像学及血栓病理的变化情况。方法健康成年杂种犬16只,其中栓塞左下肺动脉的15只按随机数字表法随机分为3组,每组5只:假手术组;1周组:5段血栓柱栓塞,观察1周;2周组:5段血栓柱栓塞,观察2周。另外1只将血栓柱栓塞至右下肺动脉以证实选择性栓塞的可行性,观察2周。观察指标为动脉血气、血液动力学参数及局部肺动脉造影影像学变化。实验犬经血栓栓塞制模后肌注氨甲环酸,1、2周后解剖观察栓塞情况;应用磷钨酸苏木精染色(PTAH)观察血栓的病理变化。结果犬肺血栓栓塞前,氧合指数(PaO_2/FiO_2)为(508±58)mm Hg(1 mm Hg=0.133 kPa),栓塞1 h 后为(395±100)mm Hg;栓塞前平均肺动脉压(MPAP)为(15±3)mm Hg,栓塞1 h后为(21±4)mm Hg;肺血管阻力(PVR)栓塞前为(178±114)mm Hg·s/L,栓塞1 h后为(404±260)mm Hg·s/L,差异均有统计学意义(均 P<0.05)。实验犬肺动脉栓塞后局部肺动脉造影可见截断征;1周时见栓塞近端肺动脉明显增粗,管壁僵硬样改变等。栓塞1、2周时解剖发现实验犬肺动脉内血栓表面不平滑;PTAH 染色见血栓表面机化,2周组见血栓内多处再通,肺动脉壁增生组织包绕、分割血栓。结论将血栓柱栓塞犬肺叶动脉,并用氨甲环酸抑制纤溶,可建立模拟慢性 PTE 部分病理改变的动物模型;栓塞不同时间,肺动脉造影表现不同;时间越长,血栓机化越明显。     

建立监测血流动力学变化的兔急性肺血栓栓塞模型

目的应用猪尾导管建立能够监测血流动力学变化的兔急性肺血栓栓塞(PTE)模型。方法试验兔24只随机分为PTE组和对照组,每组12只,均建立右侧颈静脉和左侧颈动脉通路。PTE组经导管注入自体血栓3个,通过肺动脉造影评估PTE模型是否成功,监测肺动脉压力和血气分析等变化。结果造模成功率100%。PTE组肺动脉造影显示,右心室扩张,肺动脉增粗、充盈缺损、截断或完全缺失。造模后,PTE组较造模前和对照组肺动脉平均压明显增高[(16.40±1.82)mm Hg vs(9.60±2.07)mm Hg和(11.17±2.14)mm Hg,1 mm Hg=0.133kPa,P=0.01,P=0.002]。血气分析显示,造模后PTE组较造模前pH、PO2、标准碳酸氢盐、血氧饱和度以及动脉/肺泡氧分压等指标明显降低,肺泡动脉氧分压差明显增加。结论经颈静脉送入猪尾导管建立兔急性PTE模型成功率较高,重复性较好,且能够监测血流动力学变化,为PTE诊治的相关研究提供了实验基础。     

尿激酶免疫脂质体靶向溶栓治疗兔肺动脉血栓栓塞

目的 观察以抗纤维蛋白D-二聚体单克隆抗体(DDmAb)为靶向装置的血栓靶向尿激酶(urokinase,UK)免疫脂质体(liposome,Lip)的溶栓效果.方法 新西兰大白兔32只,随机分为4组,每组8只,每只兔均采用自体血栓栓子颈静脉注入法建立急性肺动脉血栓栓塞模型.各组经股静脉输入不同溶栓剂进行溶栓治疗,通过观察右心室压变化及比较肺内残留栓子评价各组溶栓疗效.4组分别为阴性对照组(输入TBS缓冲液),阳性对照组(输入15万IU/kg UK),UK-Lip组(输入3万IU/kg尿激酶脂质体,反相蒸发法制备),DDmAb-UK-Lip组(输入3万IU/kg尿激酶免疫脂质体,戊二醛交联法连接UK-Lip和DDmAb制备).结果 栓塞后各组右心室压均明显升高(P均<0.01),平均升高(6.75±6.82)mm Hg(1 mm Hg=0.133 kPa).阴性对照组溶栓结束时右心室压[(40.15±11.22)mm Hg]与溶栓即刻[(41.67±14.23)mm Hg]相比下降轻微,阳性对照组和DDmAb-UK-Lip组降到与正常近似[阳性对照组和DDmAb-UK-Lip组溶栓结束时与栓塞前右心室压分别为(34.71±8.67)mm Hg比(33.98±9.32)mm Hg和(30.65±6.67)mm Hg比(30.77±6.85)mm Hg,P均>0.05],UK-Lip组情况居于阴性对照组和阳性对照组及DDmAb-UK-Lip组之间.阳性对照组及DDmAb-UK-Lip组栓子溶解最充分,残留柃子数近似(P>0.05),UK-Lip组栓子部分溶解,阴性对照组栓子未溶解.阳件对照组的心、肝、肾组织明显出血,其他组内脏未见明显病理学改变.结论 DDmAb-UK-Lip治疗急性肺动脉血栓栓塞的尿激酶用量仪为单独应用尿激酶的1/5即达到相似的溶栓效果,且不良反应较少,以DDmAb-UK-Lip进行靶向溶栓可能是肺动脉血栓栓塞的一种理想溶栓方式.     

结缔组织病相关肺动脉高压模型的建立

目的 通过成年SD大鼠腹腔一次性注射野百合碱,构建结缔组织病相关肺动脉高压模型方法的可行性.方法 实验组一次性腹腔注入1％野百合碱溶液,剂量为50 mg/kg,对照组腹腔注入同体积2:8无菌乙醇和0.9％氯化钠注射液.2、4周后通过计算机控制多功能生理仪行血流动力学检测,通过肺组织病理学观察异硫氰酸荧光素( FITC).凝集素灌注和抗α.平滑肌肌动蛋白(α-SMA)荧光标记了解肺血管重构情况.2组间比较采用t检验.结果 腹腔注射1％野百合碱溶液4周后,模型动物肺动脉测压[肺动脉收缩压(PASP)(41±6) mm Hg,肺动脉舒张压(PADP)(24.3±3.8) mm Hg,平均肺动脉压(mPAP)(29.8±4.2) mm Hg],与对照组[PASP (23±3) mm Hg;PADP (8.5±2.4) mm Hg;mPAP (17.1±2.5) mm Hg]比较,明显升高(P＜0.05),实验组肺组织病理学检查显示肺小动脉管壁增厚、管腔狭窄,肺小动脉管壁厚度指数(TI) 0.723±0.034和面积指数(AI) 0.912±0.203明显高于对照组(0.314±0.023和0.414±0.021)(P＜0.05).结论 SD大鼠腹腔注射野百合碱4周后,可形成肺动脉高压模型,该模型与临床结缔组织病相关肺动脉高压的病理生理相接近,且稳定、可靠、经济.     

实验性肺血栓栓塞症大鼠肺炎症反应的变化及阿托伐他汀的干预作用

目的探讨实验性肺血栓栓塞症大鼠肺炎症反应的变化及阿托伐他汀的干预作用。方法 42只大鼠随机分为假手术组(Sham组)、肺栓塞模型组(PTE组)、阿托伐他汀干预组(Statin组)。采用自体血栓回输法建立肺栓塞大鼠动物模型,取动脉血行血气分析,取肺组织行常规病理检查,免疫组化测定P38促分裂原活化蛋白激酶(P38MAPK)及TNF-α在肺组织中的表达。结果 PTE组明显缺氧,且肺组织炎症损伤较Statin组明显。PTE组肺组织P38MAPK、TNF-α表达较Sham组表达增强,Statin组与PTE组相比表达减弱,差异均有统计学意义(P均<0.05)。结论急性肺动脉栓塞可引起P38MAPK信号通路参与的炎症反应的激活,阿托伐他汀可以从某种程度上抑制P38MAPK、TNF-α的表达,从而减轻炎症反应。     

实验性急性肺栓塞溶栓疗法与动脉血浆内皮素水平变化

目的：自体血栓注入法建立急性肺栓塞动物模型，探讨内皮素在急性血栓栓塞性肺动脉高压中的作用和溶栓疗法对肺动脉释放内皮素的影响。方法：14只杂种犬，自体血栓注入法建立急性肺栓塞模型。模型犬随机分入溶栓组和对照组，溶栓组7只犬给予尿激酶20000U/kg，100ml液体稀释后30分钟静脉滴入，对照组同期输入等量的生理盐水。分别于注栓前、溶栓前（对照组同期）、溶栓后（对照组同期）血液动力学测定，采动脉血放免法测定血浆内皮素水平。结果：溶栓组犬静注尿激酶30分钟后，伴随肺动脉压力和肺血管阻力的显著性下降，动脉血浆内皮素水平显著升高，溶栓后30小时为99.25±12.90pg/L，与注栓前51．63±10．09pg/L比较P＜005，与对照组同期值55．93±2.10pg/L比较P＜001，对照组犬栓塞后4小时内肺动脉压力和肺血管阻力无显著变化，内皮素水平亦无显著性改变。结论：内皮素可能与急性血栓栓塞性肺动脉高压的形成有关，动脉血浆内皮素水平的增加可能是血管再通的一个标志。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.