Studies on the action of bacterial thiol-activated hemolysins on endothelial cells of pulmonary circulation.

用全鼠、离体主动脉环和培养的血管内皮细胞，研究了细菌硫醇激活的溶血素肉毒梭菌的肉毒杆菌溶血素和产气荚膜梭菌的theta毒素对动物肺循环的影响。染毒1,000 HU的大鼠出现左心衰竭，并伴有进行性心动过缓和低血压，死亡15.6(SY.+-)。[)注射毒素后2分钟。另一方面，10000HU的theta毒素中毒的大鼠表现为右心衰竭伴心动过速、肺水肿、右房和右室腔血栓形成以及肝脏充血，死亡21.8(]sy.+-)。[)注射后2.8分钟。离体大鼠心脏灌流灯盏花素可明显增加冠脉循环阻力，而灌流Theta毒素的作用不明显。两种溶血素均可抑制乙酰胆碱引起的大鼠离体主动脉环内皮依赖性松弛。1HU/mlBL和1HU/mltheta毒素对乙酰胆碱的量效曲线右移幅度基本相同。与其他有核哺乳动物细胞相比，猪和猪主动脉内皮细胞对这两种溶血素非常敏感。在体外培养的猪和豚鼠血管内皮细胞中，50%有效浓度的青蒿素和西他毒素对猪和豚鼠血管内皮细胞的细胞毒作用无明显差异。Theta毒素优先作用于肺循环系统，而BL优先作用于冠状循环系统，尽管两种溶血素在体外和现场对主动脉内皮细胞的作用相似。结果提示，theta毒素可能是成人气性坏疽呼吸窘迫综合征的致病因素。

Effects of bacterial thiol-activated hemolysins, botulinolysin (BL) of Clostridium botulinum and theta toxin of C.perfringens, on the pulmonary circulation of the animals were studied using whole rats, isolated aortic rings, and cultured endothelial cells.1. Rats intoxicated with 1,000 HU of BL showed left heart failure with progressive bradycardia and hypotension, and died 15.6(]SY.+-。[)2,0 min after the toxin injection. On the other hand, rats intoxicated with 10,000 HU of theta toxin showed right heart failure with tachynea, lung edema, clot formation in right atrial and ventricular cavities, and liver congestion, and died 21.8(]SY.+-。[)2.8 min after the injection.2. In vitro perfusion of BL into isolated rat hearts caused marked increase in resistance of coronary circulation while perfusion of theta toxin did just a little.3. Acetylcholine-induced endothelium-dependent relaxation of isolated rat aortic rings was inhibited by both hemolysins. The extent of rightward shifts of concentration-response curve of acetylcholine by 1 HU/ml of BL and 1 HU/ml of theta toxin were almost the same.4. Swine and gunea pig aortic endothelial cells were very much sensitive to both hemolysins comparing with other nuclearated mammalian cells in culture. No significant difference was obserrved between 50% effective concentrations of BL and that of theta toxin in their cytotoxic action against swine and guinea pig endothelial cells culture.The results obtained in this study show taht both hemolysins act on endothelial cells in vivo. Theta toxin preferentially acts on the pulmonary circulation system while BL acts preferentially on the coronary circulation system, though both hemolysins act similarly on aortic endothelial cells in vitro and in site. The results suggest theta toxin as a possible causative agent for adult respiratory distress syndrome in gas gangrenes.