摘要
目的观察百草枯(paraquat,PQ)中毒肾组织中诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)的表达及褪黑素对其的影响,进一步探讨其病理生理机制。方法 SD大鼠126只随机分为正常对照组(A组)、PQ中毒组(B组)和褪黑素(melatonin,MT)治疗组(C组),每组42只。B、C组腹腔注射PQ(25 mg/kg),A组腹腔注射等量生理盐水,15min后C组腹腔注射MT(10 mg·kg·d^(-1))。观察肾组织病理学变化及iNOS表达。结果①A组大鼠镜下肾组织结构清晰,未见充血、水肿及空泡变性等病理变化;B组肾组织结构清晰度下降,中毒后3h即可见充血、水肿及空泡变性等病理变化,1d达顶峰,其后缓解趋势不明显;C组病理变化明显减轻且缓解趋势明显。②A组iNOS多不表达,少数标本可有皮质部肾小管上皮细胞、肾小球内皮细胞胞浆弱表达。B组中毒后3h在皮质部肾小管上皮细胞及肾小球内皮细胞的胞浆中表达增加,随时间延长明显增强,1d达高峰,其后维持较强表达水平;C组亦出现表达,但表达水平较B组降低,1d达高峰,其后减弱,3d后维持在较低水平,5d时所有标本仍均有表达,6h～5d差异有统计学意义(P<0.05)。结论 iNOS参与了PQ中毒肾损伤的发病过程;MT对PQ中毒肾组织有保护作用,其可能是通过抑制iNOS起作用,但其调节途径尚需进一步探讨。
Objective To study the mechanism of paraquat(PQ)-induced renal injury in rats,the expression changes of inducible nitric oxide synthase(iNOS)and the protection effect of melatonin.Methods One hundred and twenty-six adult healthy Sprague-Dawley(SD)rats were randomly divided into three groups,the control group(group A)(n=42),the paraquart poisoned group(group B)(n=42)and melatonin(MT)group(group C)(n=42).The rats in group B and group C were treated with PQ(25 mg/kg)intraperitoneally,the rats in group A were treated with the same dose of normal saline.Fifteen minutes later,the rats in group C were given MT intraperitoneally at a dose of 10 mg/kg?d^(-1)and the rats in group A and B were treated intraperitoneally with the same dose of normal saline.The histopathological changes and the expression of iNOS were observed with immunohistochemistry(IHC).Results ①In group A,the tissue structure is clear without edema,vacuolar degeneration,cloudy swelling and necrosis.In group B,there were obvious lesions in the renal tubule of cortical part,including cellular swelling, the narrow canula,the mesenchymal congestion and edema.These pathologic changes gradually reached the peak on the first day,and did not relieve till the end of this study;Compared with group B,the aforementioned pathological lesion was more palliative in group C.②In group A, there was no or weak expression of iNOS.On 3 hours after poisoning,the expressions of iNOS in group B were observed in the cytoplasm of renal tubular epithelial cells and glomerular endothelial cells of cortical part.It reached the peak on the first day and continued at a high level after that. Compared with group A,the expressions of iNOS were observed at the third hour in group C too. And compared with group B,iNOS in group C were lower,and reached the peak on the first day. It continued at a low level after third day.There was statistical difference between group C and group B from the sixth hour to the fifth day(P<0.05).Conclusion iNOS was involved in the procedures of renal injury;MT surely had a protective effect,which might be mediated by iNOS in the paraquat-induced renal injury,but its regulation path still need a further exploration.
出处
《河北医科大学学报》
CAS
2009年第10期1001-1004,插27,共5页
Journal of Hebei Medical University
基金
2007年度河北省科技攻关计划指导项目(072361243)
2009年邯郸市科学技术研究发展计划项目(0923108054-3)
关键词
百草枯
肾
一氧化氮合酶
paraquat
kidney
nitric-oxide synthase
