目的 探讨姜黄素能否诱导大鼠肾内血红素氧合酶1(HO-1)表达,并防治对比剂肾病.方法 24只SD雄性大鼠按区组随机化方法分为4组,分别为对照组(A组,6例)、单纯泛影葡胺组(B组,6例)、泛影葡胺+姜黄素组(C组,6例)、泛影葡胺+姜黄素+锌原卟Ⅸ组(D组,6例).适应性喂养1周后,在全身麻醉下切除各组大鼠的右肾,继续普通饲料喂养4周.随后,除A组仍以普通饲料喂养外,其余3组给予去盐饮食,且各组大鼠均每天肌肉注射速尿1次(2 mg/kg),连续7d.在第7天初,C组肌肉注射1次姜黄素(20mg/kg),D组肌肉注射1次姜黄素(20mg/kg)和锌原卟Ⅸ(7.5 mg/kg),A、B两组肌肉注射等量的生理盐水各1次.在第7天末,各组经尾静脉注入吲哚美辛10mg/kg;1 h后,分离一侧颈总动脉并插管,B、C、D3组按8ml/kg注入60％泛影葡胺,A组则注入等量生理盐水.48 h后处死动物,取血液及肾组织备检.比较各组血清肌酐、HO-1表达量、HO-1活性、Bax、Bcl-2和凋亡指数.结果 B、C、D组血清肌酐[分别为(83.67±4.50) μmol/L、(63.67 ±4.76)μmol/L、(104.17 ±4.58) μmol/L]均高于A组[(41.50 ±5.58) μmol/L;P均＜0.05]；B组血清肌酐高于C组,而低于D组(P均＜0.05).B、C、D组HO-1表达量均高于A组(P均＜0.05)；B、D两组HO-1表达量低于C组(P均＜0.05).A、B、C组HO-1活性均高于D组(P均＜0.05)；B组HO-1活性高于A组,而低于C组(P均＜0.05).B、C、D组的Bcl-2、Bax、凋亡指数均高于A组(P均＜0.05),而Bcl-2/Bax低于A组(P均＜0.05)；与B组比较,C组的Bcl-2和Bcl-2/Bax较高,Bax和凋亡指数较低(P均＜0.05),而D组Bcl-2和Bcl-2/Bax较低,Bax和凋亡指数较高(P均＜0.05).结论 姜黄素可诱导在体肾组织HO-1表达,并通过HO-1抑制肾脏细胞凋亡,防治对比剂肾病.%Objective To explore the effect of curcumin (CMN) on contrast-induced nephropathy (CIN) in rats and explore the potential mechanisms focusing on heme oxygenase-1 (HO-1)expression.Methods Male SD rats (n =24) were randomly divided into four groups (n =6 each): control group (group A),diatrizoate group(DTZ,group B),DTZ + CMN group (group C),DTZ + CMN + zinc protoporphyrin Ⅸ group (group D).All rats were fed with normal chow for 1 week,right kidney was excised under anesthesia and rats were fed with normal chow for another 4 weeks.Mterwards,rats in group A was fed with normal chow,and rats in group B to D were fed with low-salt diet.All rats were injected furosemide 2 mg · kg-1 · d-1 for 7 days intramuscularly.At the beginning of the 7th day,rats in group C were injected intramuscularly with CMN 20 mg/kg,rats in group D were injected with CMN (20 mg/kg) + zinc protoporphyrin Ⅸ (7.5 mg/kg) while rats in group A and B were injected with equal volume of physiological saline.At the end of the 7th day,indometacin (10 mg/kg) was injected into tail vein of all rats.One hour later,60％ DTZ (8 ml/kg) was injected to rats in the group B,C and D while equal volume saline was injected to rats in group A through common carotid artery.After 48 hours,blood was drawn from the hearts of deeply anesthetized rats and kidney tissue was obtained for histology,HO-1,Bax,Bcl-2 expression and the apoptotic index measurements.Results The serum creatinine of group B,C and D [(83.67 ± 4.50)μmol/L,(63.67 ±4.76) μmol/L,(104.17 ±4.58) μmol/L] was significantly higher than that of group A [(41.50 ±5.58) μmol/L,all P ＜0.05],the serum creatinine was significantly higher in group B than in group C and lower than in group D (all P ＜ 0.05).HO-1 expression of group B,C and D was significantly higher than that of group A(all P ＜0.05),significantly higher in group C than in group B and D (all P ＜0.05).HO-1 activity of group A,B and C was significantly higher than that of group D (all P ＜ 0.05),HO-1 activity was significantly higher in group B than in group A and significantly lower in group B than in group C (all P ＜ 0.05).Bax,Bcl-2 expression and apoptosis index of group B,C and D were significantly higher than that of group A (all P ＜ 0.05),while Bcl-2/Bax of group B,C and D were significantly lower than that of group A(all P ＜ 0.05).Bcl-2 and Bcl-2/Bax were significantly higher while apoptosis index was significantly lower in group C than in group B (all P ＜ 0.05).Bax and apoptosis index were significantly higher and Bcl-2,Bcl-2/Bax were significantly lower in group D than in group B(all P ＜ 0.05).Conclusion CMN could protect against contrast-induced nephropathy through reducing renal cell apoptosis via upregulating HO-1 expression and activating HO-1 activity in rats.
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