蝮蛇抗栓酶治疗高粘滞血症23例甲襞微循环的观察（摘要）

蝮蛇抗栓酶治疗高粘滞血症２３例甲襞微循环的观察（摘要）南京市钟山医院张思效本文对２３例高粘滞血症患者在用蝮蛇抗栓酶治疗前后以甲襞微循环进行对比观察,证明治疗后甲襞微循环状态有显著改善。从加权积分值变化可以看出;管袢形态Ｐ＜０．００５,管袢流态Ｐ＜０．...     

蝮蛇抗栓酶治疗高粘滞血症的血流变学研究（附47例分析）

本文报道采用蝮蛇抗栓酶治疗血液粘度异常以上的高粘滞血症４７例,以复方丹参对照观察,两组治疗１～２疗程后,复查血液粘度恢复正常者,抗栓酶治疗组占６８％,复方丹参治疗组占６０％;两种药物对降低全血粘度,血球压积,加快红细胞电泳均有明显作用;抗栓酶对降低纤维蛋白原和男性的全血粘度较复方丹参作用更显著,是治疗高粘滞血症一种较理想的药物,也可作为心脑缺血性血管疾病的预防治疗。     

肺血管EDNO及其合酶在大鼠低氧性肺动脉高压形成中的作用

本研究观察了低氧对大鼠肺组织和血管内皮一氧化氮合酶（ＮＯＳ）活性及内皮衍生一氧化氮（ＥＤＮＯ）依赖性舒张反应的影响,以及ＮＯＳ抑制剂（Ｌ－ＮＡＭＥ）对常氧和低氧大鼠肺组织和血管内皮ＮＯＳ活性及颈、肺动脉血压（ＣＡＰｓ、ｍＰＡＰ）的作用。结果表明常氧大鼠肺泡内无肌性血管内皮未见ＮＯＳ活性,其肺血管床对ＥＤＮＯ依赖性舒血管物质ＢＫ没有反应,注射Ｌ－ＮＡＭＥ后大鼠ｍＰＡＰ略有降低,ＣＡＰｓ有所升高。低氧大鼠肺泡内无肌性血管内皮显示ＮＯＳ活性,对ＢＫ的ＥＤＮＯ依赖性舒张反应呈剂量依赖性增大,注射Ｌ－ＮＡＭＥ使低氧大鼠ｍＰＡＰ显著降低（Ｐ＜０．０１）,ＣＡＰｓ显著升高（Ｐ＜０．０５）。提示肺血管ＥＤＮＯ及其合酶在维持正常成年大鼠肺循环低压低阻中的生理作用值得进一步探讨;低氧引起肺血管内皮ｅｃＮＯＳ活性增加和ＥＤＮＯ生成增多可能起到限制肺动脉压过度升高的调制作用,也可能对肺血管内皮产生毒性作用,反而促进肺动脉高压的发生和发展。     

精制蝮蛇抗栓酶治疗迟发性运动障碍

目的：验证精制蝮蛇抗栓酶对迟发性运动障碍的疗效。方法对８例符合ＳｃｈｏｏｌｅｒＴＤ诊断标准的精神分裂症病人,在原抗精神病药物治疗不变的基础上加用蝮蛇抗栓酶,治疗３个疗后（１５天为１个疗程,每疗程间歇期３－７天）用ＴＤＲＳ、ＡＩＭＳ、ＢＰＲＳ和ＴＥＳＳ在应用抗栓酶前后及各疗程末进行评定,并进行自身配对比较分析,结果加用精制蝮蛇抗栓酶治疗３个疗程后ＴＤＲＳ、ＡＭＩＳ、ＢＰＲＳ总分明显降低（Ｐ〈０．０１     

以经颅多普勒血流仪对蝮蛇抗栓酶与速效溶栓清治疗缺血性脑血管病颅内动脉血流变化的观察

６２例缺血性脑血管病患者,其中４２例为蝮蛇抗栓酶治疗组,２０例为速效溶栓清治疗组。治疗前后分别用经颅多普勒血流仪（ＴＣＤ）检查脑血管（大脑中动脉ＭＣＡ、前动脉ＡＣＡ及后动脉ＰＣＡ）血流平均值Ｖｍ。结果显示,两组患者被治疗后脑血管血流Ｖｍ均明显增高（Ｐ＜０．０５或Ｐ＜０．０１）,但两组间无显著性差异（Ｐ＞０．０５）。表明两种药物治疗缺血性脑血管病疗效相仿,但速效溶栓清价格较高     

蝮蛇抗栓酶,丹参注射液对高粘状态血液流变学影响的对比观察

本文应用蝮蛇抗栓酶(清栓酶)和丹参注射液对高血压、冠心病、脑动脉硬化并有高粘状态84例进行治疗,其中清栓酶组50例;丹参组34例。检测血球压积,全血比粘度、全血还原粘度、血浆比粘度、红细胞电泳、纤维蛋白原、血沉等7项血液流变学指标,并进行治疗前后对比观察。经统计学处理后发现抗栓酶组的治疗效果明显优于丹参组(P<0.005)。抗栓酶有大幅度降低纤维蛋白原的作用。所以蝮蛇抗栓酶是目前应用于血栓病。血液高粘滞血症HVS等病症较为理想的药物。     

蝮蛇抗栓酶冲击疗法治疗急性心肌梗塞17例

蝮蛇抗栓酶冲击疗法治疗急性心肌梗塞１７例张卫明,苏世祯永福县人民医院５４１８００本文１７例诊断急性心肌梗塞（ＡＭＩ）,为１９８９～１９９３年住院病人。采用蝮蛇抗栓酶［沈阳第一制药厂生产的江浙蝮蛇抗栓酶,每支含０．２５ｕ,Ｓｖａｔｅ,皮试阴性。］０．７...     

蝮蛇抗栓酶3号对心血管病高凝状态的影响

应用蝮蛇抗栓酶３号（以下简称Ｓｖａｔｅ—３）治疗心血管病高凝状态２４例,剂量１．０ｕ稀释后静滴,ｑｄ,３周为一疗程。治疗后患者全血粘度、血浆粘度、血小板聚集率、组织纤溶酶原激活物抑制剂（ＴＰＩ）、血栓素Ｂ２（ＴＸＢ２）、组织纤维连结蛋白（ＦＮ）均有显著下降,而组织纤溶酶原激活剂（ＴＰＡ）、６－酮前列腺素Ｆα（６－Ｋｅｔｏ－ＰＧＦα）明显升高。提示,该药治疗心血管病高凝状态有效。     

蝮蛇抗栓酶治疗高粘滞综合征40例血液流变学观察

蝮蛇抗栓酶治疗高粘滞综合征４０例血液流变学观察武汉市第五医院二桥门诊部周玉祥国内外大量文献报导冠心病,高血压病,脑血管意外的病人血液呈高粘滞状态,是造成这些疾病发生和发展的病理基础之一。笔者近几年来与武汉市针灸医院采用蝮蛇抗栓酶治疗本病,取得满意疗效...     

蝮蛇抗栓酶治疗高脂血症及心电图分析

应用蝮蛇抗栓酶治疗高脂血症３８例,１个月后观察血脂下降、血液流变学改善（Ｐ＜０．０５）、心电图改善,总有效率７５％,尤其是对ＳＴ—Ｔ异常、早博的疗效较好。     

脉络宁合用蝮蛇抗栓酶治疗中风后遗症101例疗效评价

通过观察脉络宁合用蝮蛇抗栓酶分型治疗中风后遗症１０１的临床疗效,并与单用脉络宁对照组６９例比较。从而初步探讨２药联用对各型病例效应的机理,为优选本病的药疗方案提供参考资料。结果治疗组总有效率及中药病例有效率均显著高于对照组;各型病例治愈率及轻、重型病例有效率、重型患者显效率也都比对照组高;但各型病例好转率及轻、中型病例显效率２组结果无显著差异。     

两种蝮蛇抗栓酶与传统方法治疗缺血性脑卒中146例的疗效分析

采用东北白眉蝮蛇抗栓酶、江浙蝮蛇抗栓酶、丹参加低右治疗缺血性脑卒中,以一般对症处理治疗作为对照组结果显示东北白屑蝮蛇抗栓酶治疗缺血性脑卒中与对照组比较 P 值有显著性差异,而其他两组与对照组比较 P 值无显著性差异.     

蝮蛇抗栓酶治疗小儿脑炎致急性偏瘫血中6—K—PGF1α,TXB2的变化

应用蝮蛇抗栓酶治疗小儿脑炎致急性偏瘫共25例。沿疗前后检测血中的6-K-PGF_1x及 TXB_2.结果表明:治疗后血中 6-酮-前列腺素 F_1x 明显增高,血栓素 B_2明显降低。推测蝮蛇抗栓酶之所以具有去纤、溶栓、扩血管等作用,可能与血中前列腺素、血栓素 B_2水平变化有关。     

Mesenchymal stem cells ameliorate silica-induced pulmonary fibrosis by inhibition of inflammation and epithelial-mesenchymal transition

Silicosis is a devastating occupational disease caused by long-term inhalation of silica particles, inducing irreversible lung damage and affecting lung function, without effective treatment. Mesenchymal stem cells (MSCs) are a heterogeneous subset of adult stem cells that exhibit excellent self-renewal capacity, multi-lineage differentiation potential and immunomodulatory properties. The aim of this study was to explore the effect of bone marrow-derived mesenchymal stem cells (BMSCs) in a silica-induced rat model of pulmonary fibrosis. The rats were treated with BMSCs on days 14, 28 and 42 after perfusion with silica. Histological examination and hydroxyproline assays showed that BMSCs alleviated silica-induced pulmonary fibrosis in rats. Results from ELISA and qRT-PCR indicated that BMSCs inhibited the expression of inflammatory cytokines TNF-α, IL-1β and IL-6 in lung tissues and bronchoalveolar lavage fluid of rats exposed to silica particles. We also performed qRT-PCR, Western blot and immunohistochemistry to examine epithelial-mesenchymal transition (EMT)–related indicators and demonstrated that BMSCs up-regulate E-cadherin and down-regulate vimentin and extracellular matrix (ECM) components such as fibronectin and collagen Ⅰ. Additionally, BMSCs inhibited the silica-induced increase in TGF-β1, p-Smad2 and p-Smad3 and decrease in Smad7. These results suggested that BMSCs can inhibit inflammation and reverse EMT through the inhibition of the TGF-β/Smad signalling pathway to exhibit an anti-fibrotic effect in the rat silicosis model. Our study provides a new and meaningful perspective for silicosis treatment strategies.     

Surfactant protein A prevents silica-mediated toxicity to rat alveolar macrophages

Silicosis is a serious occupational lung disease associated with irreversible pulmonary fibrosis. The interaction between inhaled crystalline silica and the alveolar macrophage (AM) is thought to be a key event in the development of silicosis and fibrosis. Silica can cause direct injury to AMs and can induce AMs to release various inflammatory mediators. Acute silicosis is also characterized by a marked elevation in surfactant apoprotein A (SP-A); however, the role of SP-A in silicosis is unknown. We investigated whether SP-A directly affects the response of AMs to silica. In this study, the degree of silica toxicity to cultured rat AMs as assessed by a (51)Cr cytotoxicity assay was shown to be dependent on the time of exposure and the concentration and size of the silica particles. Silica directly injured rat AMs as evidenced by a cytotoxic index of 32.9 +/- 2.5, whereas the addition of rat SP-A (5 microg/ml) significantly reduced the cytotoxic index to 16.6 +/- 1.2 (P < 0. 001). This effect was reversed when SP-A was incubated with either polyclonal rabbit anti-rat SP-A antibody or D-mannose. These data indicate that SP-A mitigates the effect of silica on AM viability, and this effect may involve the carbohydrate recognition domain of SP-A. The elevation of SP-A in acute silicosis may serve as a normal host response to prevent lung cell injury after exposure to silica.     

MiR‐503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica‐induced pulmonary fibrosis

Inhalation and deposition of crystalline silica particles in the lung can cause pulmonary fibrosis, then leading to silicosis. Given the paucity of effective drugs for silicosis, new insights for understanding the mechanisms of silicosis, including lung fibroblast activation and myofibroblast differentiation, are essential to explore therapeutic strategies. Our previous research showed that the up‐regulation of miR‐503 alleviated silica‐induced pulmonary fibrosis in mice. In this study, we investigated whether miR‐503 can regulate the TGF‐β1‐induced effects in lung fibroblasts. Mimic‐based strategies aiming at up‐regulating miR‐503 were used to discuss the function of miR‐503 in vivo and in vitro. We found that the expression level of miR‐503 was decreased in fibroblasts stimulated by TGF‐β1, and the up‐regulation of miR‐503 reduced the release of fibrotic factors and inhibited the migration and invasion abilities of fibroblasts. Combined with the up‐regulation of miR‐503 in a mouse model of silica‐induced pulmonary fibrosis, we revealed that miR‐503 mitigated the TGF‐β1‐induced effects in fibroblasts by regulating VEGFA and FGFR1 and then affecting the MAPK/ERK signalling pathway. In conclusion, miR‐503 exerted protective roles in silica‐induced pulmonary fibrosis and may represent a novel and potent candidate for therapeutic strategies in silicosis.     

The central role of Fas-ligand cell signaling in inflammatory lung diseases

Following inflammation and injury in the lung, loss of epithelial cell precursors could determine the balance between tissue regeneration and fibrosis. This review discusses evidence that proapoptotic Fas-Fas ligand (FasL) signaling plays a central role in pulmonary inflammation, injury and fibrosis. FasL signaling induces inflammatory apoptosis in epithelial cells and alveolar macrophages, with concomitant IL-1 beta and chemokine release, leading to neutrophil infiltration. FasL signaling plays a critical role in models of acute lung injury, idiopathic pulmonary fibrosis and silicosis; blockade of Fas-FasL interactions either prevents or attenuates pulmonary inflammation and fibrosis. Serologic and immunohistochemical studies in patients support a major pathogenic role of Fas and FasL molecules in inflammatory lung diseases. Identification of the pathogenic role of FasL could facilitate the discovery of more effective treatments for currently untreatable inflammatory lung diseases.     

Effect of inhaled crystalline silica in a rat model: time course of pulmonary reactions

Numerous investigations have been conducted to elucidate mechanisms involved in the initiation and progression of silicosis. However, most of these studies involved bolus exposure of rats to silica, i.e. intratracheal instillation or a short duration inhalation exposure to a high dose of silica. Therefore, the question of pulmonary overload has been an issue in these studies. The objective of the current investigation was to monitor the time course of pulmonary reactions of rats exposed by inhalation to a non-overload level of crystalline silica. To accomplish this, rats were exposed to 15 mg/m3 silica, 6 h/day, 5 days/week for up to 116 days of exposure. At various times (5-116 days exposure), animals were sacrificed and silica lung burden, lung damage, inflammation, NF-KB activation, reactive oxygen species and nitric oxide production, cytokine production, alveolar type II epithelial cell activity, and fibrosis were monitored. Activation of NF-KB/DNA binding in BAL cells was evident after 5 days of silica inhalation and increased linearly with continued exposure. Parameters of pulmonary damage, inflammation and alveolar type II epithelial cell activity rapidly increased to a significantly elevated but stable new level through the first 41 days of exposure and increased at a steep rate thereafter. Pulmonary fibrosis was measurable only after this explosive rise in lung damage and inflammation, as was the steep increase in TNF-alpha and IL-1 production from BAL cells and the dramatic rise in lavageable alveolar macrophages. Indicators of oxidant stress and pulmonary production of nitric oxide exhibited a time course which was similar to that for lung damage and inflammation with the steep rise correlating with initiation of pulmonary fibrosis. Staining for iNOS and nitrotyrosine was localized in granulomatous regions of the lung and bronchial associated lymphoid tissue. Therefore, these data demonstrate that the generation of oxidants and nitric oxide, in particular, is temporally and anatomically associated with the development of lung damage, inflammation, granulomas and fibrosis. This suggests an important role for nitric oxide in the initiation of silicosis.     

Type 2 immune response associated with silicosis is not instrumental in the development of the disease

It has been proposed that the development of lung fibrosis is associated with a T helper type 2 response, mainly characterized by IL-4 and IL-13 production. We investigated the potential role of type 2 immune polarization in the silicotic process and examined the pulmonary response to silica particles in mice genetically deficient for IL-4. We found that IL-4(-/-) mice were not protected against the development of silicosis, suggesting that IL-4 is not essential for the development of this fibrotic disease. By evaluating the intensity of silica-induced lung fibrosis in mice deficient for IL-4 receptor alpha (IL-4Ralpha), we showed that the establishment of pulmonary fibrosis was independent of both IL-4 and IL-13. Strong impairment of the type 2 immune response (IgG(1)) in the lungs of IL-4(-/-) and IL-4Ralpha(-/-) mice did not affect the development of the disease. Measurement of IL-13alpha2 receptor expression and IgG(2a), IL-12p70, and IFN-gamma levels in silica-treated IL-4(-/-) and IL-4Ralpha(-/-) animals showed that the development of silicosis was not related to an IL-13 signaling pathway or a switch to a type 1 response in deficient animals. Our data clearly indicate that the type 2 immune response associated with silicosis in mice is not required for the development of this inflammatory and fibrotic disease.