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姜黄素通过上调大鼠血红素加氧酶-1表达减轻造影剂肾病

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

作者信息

Duan Bing-jun, Huang Le, Ding Hong, Huang Wei-yi

机构信息

Department of Cardiology, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2013 Feb;41(2):116-20.

Abstract

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. 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(-1)×d(-1) for 7 days intramuscularly. At the beginning of the 7(th) 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 7(th) 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.

摘要

目的

探讨姜黄素(CMN)对大鼠造影剂肾病(CIN)的影响,并以血红素加氧酶-1(HO-1)表达为重点探讨其潜在机制。

方法

雄性SD大鼠(n = 24)随机分为四组(每组n = 6):对照组(A组)、泛影葡胺组(DTZ,B组)、DTZ + CMN组(C组)、DTZ + CMN + 锌原卟啉IX组(D组)。所有大鼠正常喂养1周,麻醉下切除右肾,再正常喂养4周。之后,A组大鼠正常饮食,B至D组大鼠给予低盐饮食。所有大鼠肌肉注射速尿2 mg×kg⁻¹×d⁻¹,共7天。在第7天开始时,C组大鼠肌肉注射CMN 20 mg/kg,D组大鼠注射CMN(20 mg/kg)+ 锌原卟啉IX(7.5 mg/kg),而A组和B组大鼠注射等体积生理盐水。在第7天结束时,所有大鼠尾静脉注射吲哚美辛(10 mg/kg)。1小时后,通过颈总动脉向B、C和D组大鼠注射60% DTZ(8 ml/kg),向A组大鼠注射等体积生理盐水。48小时后,从深度麻醉的大鼠心脏取血,并获取肾组织进行组织学检查、HO-1、Bax、Bcl-2表达及凋亡指数测定。

结果

B、C和D组血清肌酐[(83.67 ± 4.50)µmol/L、(63.67 ± 4.76)µmol/L、(104.17 ± 4.58)µmol/L]显著高于A组[(41.50 ± 5.58)µmol/L,均P < 0.05];B组血清肌酐显著高于C组且低于D组(均P < 0.05)。B、C和D组HO-1表达显著高于A组(均P < 0.05),C组显著高于B组和D组(均P < 0.05)。A、B和C组HO-1活性显著高于D组(均P < 0.05),B组HO-1活性显著高于A组且显著低于C组(均P < 0.05)。B、C和D组Bax、Bcl-2表达及凋亡指数显著高于A组(均P < 0.05),而B、C和D组Bcl-2/Bax显著低于A组(均P < 0.05)。C组Bcl-2和Bcl-2/Bax显著高于B组,凋亡指数显著低于B组(均P < 0.05)。D组Bax和凋亡指数显著高于B组,Bcl-2、Bcl-2/Bax显著低于B组(均P < 0.05)。

结论

CMN可通过上调大鼠HO-1表达和激活HO-1活性,减少肾细胞凋亡,从而预防造影剂肾病。

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