抗补体蛋白对油酸型肺损伤的保护作用

THE PROTECTIVE EFFECT OF ANTICOMPLEMENTARYPROTEIN ON OLEIC ACID-INDUCED LUNG INJURY

本研究改进抗补体蛋白（ＡＣＰ）柱层析分离技术，用ＢｉｏＧｅｌＰ２００柱纯化，每次眼镜蛇毒上样量１０ｇ，ＡＣＰ回收率高达１．８％。其电泳特性和抗补体效价均和以往报道一致。ＡＣＰ４ｍｇｉｐ能使油酸的ＬＤ５０从９４．４μｇ／ｋｇ提高至２７９μｇ／ｋｇ，能预防油酸引起家兔血氧分压进行性下降和血二氧化碳分压上升，肺渗出液量和蛋白含量减少。用使补体耗竭９５％以上剂量的ＡＣＰ腹腔注射，能预防油酸引起的麻醉狗肺损伤，包括血气。肺循环。肺动态顺应性和肺病理改变改善。ＡＣＰ急性毒性低，小白鼠能耐受１次静注１０μｇ／ｋｇ而不死亡，能耗竭９８％补体剂量ＡＣＰ亦仅引起狗可恢复的肺血管阻力轻度上升，肺组织光镜检查仅有非特异性改变。说明ＡＣＰ耗竭补体可能成为有效而安全防治呼吸窘迫综合征的强有力的手段。

The anticomplementary protein (ACP) was separated and purified from the venom of Naja naja atra by improved chromatography on sephadex G75 , DEAE cellurose DE52 , and Bio gel P200 columns. The final yield reacheds 1. 8% at each loading amount of 10g crude venom. 1ts electrophoresis features and anticomple- ment activity were determined to be close to those reported previously. The protective effects of ACP on oleic acid-induced lung injury manifested in : 1. Increase in LD50 of oleic acid in mice previously given ACP ip to 279 (95% confidence limits 206-378) μg/kg, as compared with 94. 4(95% confidence limits 69. 5-129)μg/ kg in comtrol mice. 2. Prevention of hypoxemia and hypercapnea induced by oleic acid in rabbits. 3. Decrease in amount of and protein content in pulmonary exudate. 4. Improvement of respiratory distress symptoms in- cluding changes in blood gas tensions, increase in venoarterial shunt and depression in dynamic compliance in dogs. 5. Attenuation in pathological findings including hyaline membrane formation , alveolar hemorrhage and pulmonary arteriolar thrombosis. The acute toxicity of ACP was very low. Mice tolerated 10 mg/kg ACP for iv injection , ACP at dosage depleting 98% camplements only induced slight change in pulmonary va- sicular resistance in dogs. The above results suggested that depleting complements by ACP might be an effec- tive and safe measure for prevention and to treatmeant of respiratory distress syndrome.