关木通对大鼠肾上腺的毒效应及其可能机制

Toxic effects and possible mechanisms of Aristolochia manshuriensis Kom on adrenals in rats

目的观察关木通(AMK)对大鼠肾上腺的影响及其与肾损害的关系,并探讨其可能机制。方法ig给予雌性大鼠40.gkg-1.d-1AMK水煎剂1,3及5 d,观测肾上腺和肾脏的重量,肾上腺和肾脏组织学及其超微结构变化,测定血清尿素氮、肌酐和皮质醇含量,免疫组化法检测8羟-基脱氧鸟苷(8-OHdG)和诱生型一氧化氮合酶(iNOS)的表达。结果给药3 d后,大鼠血清皮质醇明显增高,肾上腺皮质明显增厚;连续给药5 d,大鼠血清尿素氮和肌酐明显增高,肾小管上皮细胞水肿,变性,坏死;给药组大鼠8-OHdG和iNOS明显表达。结论AMK可引起肾上腺皮质增生和肾损害,肾上腺损害早于肾损害,其毒效应机制可能与DNA氧化损伤和一氧化氮增多有关。

AIM To investigate the toxic effects and possible mechanism of Aristolochia manshuriensis Kom（AMK） on adrenals of rats and relationship between adrenal and kidney damage. METHODS Decoction of AMK 40 g·kg^-1·d^-1 was given ig to female rats for 1,3 and 5 d, respectively. The observed items included absolute weight and relative weight, histology and ultrastructure of adrenals and kidneys, the serum level of urea nitrogen, creatinine and cortisol, and expression of 8-hydroxydeoxyguanosine （ 8- OHdG） and inducible nitric oxide synthase （iNOS）. RESULTS After administration of AMK for 3 d, the serum cortisol level was markedly increased and adrenal cortex became thick. After administration of AMK for 5 d, urea nitrogen and creatinine significantly increased.Histologically, edema, denaturation and necrosis were observed in renal tubular epithelium. The 8-OHdG and iNOS positive cells obviously increased in treated groups. CONCLUSION AMK would induce adrenal hyperplasia and kidney damage , the occurrence was followed by kidney of adrenal damage damage. The possible toxic mechanism is related to oxidative of DNA and nitric oxide increase. damage