亚急性铁负荷增加鼠脂质过氧化物及缺血性损害敏感性

Subacute iron loading enhances peroxidation product(MDA)of kidney and susceptibility to renal ischemia in rats

因血色病中的慢性铁负荷能引起器官损伤，肾脏缺血再灌注时的损伤也与铁有关，因此我们评价了轻度亚急性铁负荷增加鼠脂质过氧化物及缺血性损害的敏感性。在实验组给雄性ＳＤ鼠腹内注射ｉｒｏｎｎｉｔｒｉｌｏｔｒｉａｃｅｔａｔｅ（Ｆｅ－ＮＴＡ）（ｌｍｇ／ｋｇ·ｄ，５ｄ），对照组鼠腹腔内注射媒介质ｎｉｔｒｉｌｏｔｒｉａｃｅ－ｔａｔｅ７２ｈ后鼠肾动脉缺血４０ｍｉｎ。铁负荷从基线增加２８％时血肌酐或组织学无任何改变。我们发现Ｆｅ－ＮＴＡ组左肾皮质ＭＤＡ量比ＮＴＡ组左肾皮质显著增加（Ｐ＜０．０１）。铁负荷组肾缺血２４ｈ、４８ｈ血肌酥显著高于对照组（３．３和３．４对２．２和０．８ｍｇ／ｄｌ），ＧＦＲ显著低于对照组（０．３对０．７８ｍｌ／ｍｉｎ）。利用半定量法评价铁负荷鼠肾组织学损害显示显著加重。

Because chronic iron overload would cause organ injury in hemochroma-tosis and because iron participated in injury during renal ischemia-reperfusionl the effectof mild subacute renal iron loading on the susceptibility to ischemic acute renal failurewas evaluated. Male Sprague-Dawley rats were injected with iron nitrilotriacetate(Fe-NTA)(1mg iron/kg,i.p daily)for five days.Controls were injected with nitrilotriace-tate (NTA)instead.Seventy-two hours later animals were subjected to 40 min renalartery ischemia.Iron loading produced a 28%increase in kidney iron content withoutany change in base line renal function (plasma creatinine)or in histology, Ischemicrenal injury was far more severe in iron-loading animals.It was found that subacutrenal iron loading increased lipid peroxidation product MDA, which was very muchhigher in the renal cortical of the left kidney of the Fe-NTA group rats than that of theNTA group( 0. 859 vs.0.555 10_(-9)M,P<0.01).Plasma creatinine a 24 and 48 hoursafter ischemia was much higher in iron-loading rats(3. 3 and4. 3 v2. 2 and 0.8mg/dl)and GFR was much lower in iron-loading rats0.30 vs.0.78 ml/mi.In addition。iron-loading rats showed a dramatical greater extent of damage by histologic evaluationusing a semi-quantitative scoring method.