亚氨乙基赖氨酸对庆大霉素所致豚鼠肾脏损伤的拮抗作用

Anti-toxical effect of iminoethyl-lysine on guinea pig renal damaged by gentamicin

目的 :探讨诱生型一氧化氮合成酶抑制剂 (in duciblenitricoxidesynthase,iNOS)亚氨乙基赖氨酸(Imi)对庆大霉素 (Gen)所致豚鼠肾脏损伤的拮抗作用。方法 :实验动物分 4组 :正常动物组、Gen组、Gen+Imi组和Imi组。Gen组和Gen+Imi组动物皮下均注射庆大霉素 1 0 0mg·kg-1·d-1日 ,连续 1 0d,同时Gen+Imi组腹腔注射Imi 1 0mg·kg-1·d-1,Gen组腹腔注射等量生理盐水 ;正常动物组皮下与腹腔均注射等量的生理盐水。Imi组腹腔注射与Gen +Imi组等量Imi。所有动物在实验前后均行肾功能检查。所有各组肾脏均行石蜡包埋、切片、HE染色、光镜观察 ;同时行iNOS免疫组织化学染色。结果 :iNOS在正常动物组和Imi组肾脏呈阴性表达 ,在Gen +Imi组和Gen组呈阳性表达 ,且Gen组iNOS活性明显强于Gen +Imi组 ;Gen组肾脏损伤明显重于Gen +Imi组。结论 :iNOS在庆大霉素所致豚鼠肾脏损伤中呈阳性表达 ,Imi显著抑制iNOS活性 ,且对肾脏损伤有明显拮抗作用 。

AIM: To investigate the anti toxic effect of iminoethyl lysine (Imi), an inhibitor of inducible nitric oxide synthase (iNOS), on the guinea pig renal injury with gentamicin (Gen). METHODS: The experiment was consisted of four groups: normal animal group, gentamicin model group (Gen group), Gen+Imi group and Imi group. Guinea pigs of both Gen group and Gen+Imi group were given (sc) Gen 100 mg·kg -1 ·d -1 for 10 d, and the guinea pigs of Gen+Imi group were treated with Imi intraperitoneally. Gen group were treated with the same volume of saline. Guinea pigs of normal animal group were treated with subcutaneous and venous injection of the same volume of saline. Guinea pigs of Imi group were treated with the same dose of Imi. The renal function of guinea pigs of all groups was examined before and after experiment. Renals of all groups were embedded with paraffin, sectioned, stained with HE, and examined with the light microscope. iNOS was examined in the kedney of all groups with immunohistochemistry. RESULTS: The expression of iNOS was negative in kidney of normal animal group and Imi group, and positive in both Gen group and Gen+Imi group. The activity of iNOS of Gen group was significantly stronger than that of Gen+Imi group. The damage of renal of Gen group was much more severely than that of Gen+Imi group. CONCLUSION: The expression of iNOS is positive in the renal damaged with Gen. Imi can significantly inhibit the activity of iNOS, and has also the significant anti toxical effect on the renals damaged with Gen. It suggests that nitric oxide takes part in the process of pathology of renals damaged by gentamicin.