LaMont J T, Sonnenblick E B, Rothman S
Gastroenterology. 1979 Feb;76(2):356-61.
The pathophysiology of antibiotic-associated colitis was studied in rabbits with severe ileocolitis induced by oral administration of clindamycin. Cell-free, sterile filtrates of cecal contents of rabbits with clindamycin colitis contained a toxin that was lethal for mice and cytotoxic for HeLa-cell monolayers. The toxin was heat labile, was inactivated by pronase but not trypsin, and had a mol wt by gel filtration on Sephadex G-100 of 45,000. The toxin was neutralized by antiserum to Clostridium perfringens type E, but not by other clostridial antisera. The toxin also caused severe necrosis of rabbit rectal epithelium during 18-hr organ culture, which could be completely reversed by neutralization with C. perfringens type E antiserum. These studies indicate that clindamycin colitis in rabbits is caused by overgrowth of a clostridial species, which releases a heat-labile toxic protein of mol wt of 45,000 capable of necrosing colonic epithelial cells.
通过口服克林霉素诱导兔发生严重回结肠炎症，研究了抗生素相关性结肠炎的病理生理学。患克林霉素结肠炎的兔盲肠内容物的无细胞无菌滤液含有一种毒素，该毒素对小鼠具有致死性，对HeLa细胞单层具有细胞毒性。该毒素对热不稳定，可被链霉蛋白酶灭活，但不被胰蛋白酶灭活，通过Sephadex G - 100凝胶过滤测得其分子量为45,000。该毒素可被产气荚膜梭菌E型抗血清中和，但不能被其他梭菌抗血清中和。在18小时的器官培养过程中，该毒素还可引起兔直肠上皮的严重坏死，而产气荚膜梭菌E型抗血清中和可使其完全逆转。这些研究表明，兔的克林霉素结肠炎是由一种梭菌属细菌过度生长引起的，该细菌释放一种分子量为45,000的对热不稳定的有毒蛋白质，能够使结肠上皮细胞坏死。
