姜黄素预诱导血红素氧合酶1表达防治对比剂肾病的实验研究

Curcumin attenuates contrast-induced nephropathy by upregulating heme oxygenase.1 expression in rat

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（2mg／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（7．5mg／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；1h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。48h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 heine 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. Afterwards, 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-~ ~ d-~ 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 〈 O. 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 〈 O. 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 〈 O. 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 〈 O. 05 ）. Conclusion CMN could protect against contrast-induced nephropathy through reducing renal cell apoptosis via upregnlating HO-1 expression and activating HO-1 activity in rats.