间充质干细胞治疗造影剂肾病的作用及机制研究

目的研究间充质干细胞(MSCs)对造影剂肾病(CIN)的预防作用及可能的机制。方法将30只SD大鼠随机分为对照组(CIN组)和MSCs组。2组大鼠均皮下注射环氧化酶抑制剂吲哚美辛(10 mg·kg-1)和一氧化氮合成酶抑制剂左旋硝基精氨酸甲酯(L-NAME,10 mg·kg-1),15 min后注射碘必乐(3 g碘·kg-1)诱导CIN。随后将大鼠麻醉,开腹,将MSCs用纤维蛋白胶混合后涂布到肾包膜上(200μL,5×106个细胞)。CIN组同样开腹,但只将纤维蛋白胶涂布到肾包膜上。每日取血测量肌酐水平。最后1日处死动物,取肾脏做HE染色和测定肾组织丙二醛(MDA)水平、过氧化氢酶(CAT)活性、谷胱甘肽过氧化物(GSH-Px)活性和总超氧化物歧化酶(T-SOD)活性。肌酐水平及各项氧化应激指标采用完全随机设计的单因素方差分析,多个样本均数间的两两比较采用t检验。结果 CIN组第24、48、72 h的肌酐水平分别为(171.00±10.15)μmol·L-1、(148.40±14.98)μmol·L-1和(98.20±8.04)μmol·L-1,而MSCs组第24、48、72 h的肌酐水平分别为(111.80±8.76)μmol·L-1、(71.01±9.27)μmol·L-1和(46.69±5.81)μmol·L-1,明显低于CIN组,该组有效抑制肾功能下降。HE染色可以看到CIN组的肾组织出现明显的空泡。而MSCs组空泡不明显。各项氧化应激指标MSCs组优于CIN组。结论 MSCs对造影剂引起的急性肾衰竭有很好的预防作用。

Mechanism and effect of mesenchymal stem cells on contrast-induced nephropathy

Objective To investigate the effi cacy and mechanism of mesenchymal stem cell（MSCs） for contrast-induced nephropathy（CIN）. Methods Totally 30 SD rats were randomized into a CIN group and an MSCs group. For inhibition of cyclooxygenase and nitric oxide synthase, the rats were injected indomethacin（10 mg·kg^-1） and NG-nitro-Larginine methyl ester（L-NAME, 10 mg·kg^- 1）, respectively. The CIN was induced with iohexol injection after 15 min. All the rats were anesthetized and paunched. MSCs mixed with fi brin glue were painted on the renal capsules of the MSCs group, but only fi brin glue was painted on the renal capsules of CIN group. Blood was collected daily to measure the creatinine level for 4 days（days 0, 1, 2, 3 or baseline and after 24, 48, and 72 h） and the rats were sacrifi ced and blood chemistry reexamined on day 3. Catalase（CAT）, glutathione peroxidase（GSH-Px）, total superoxide dismutase（TSOD） and malondialdehyde（MDA） were quantifi ed on the renal tissue. HE slides were examined. One-factor analysis of variance with completely random design was used and Student＇s t test was used in pairwise comparison between the average number with multiple samples. Results The creatinine level of the CIN group was Scr =（171.00±10.15） μmol·L^-1,（148.40±14.98） μmol·L-1 and（98.20±8.04） μmol·L-1 for 24, 48 and 72 h, respectively, with P =0.000. The MSCs protected the rats against CIN with Scr =（111.80±8.76） μmol·L^-1,（71.01±9.27） μmol·L^-1and（46.69±5.81） μmol·L-1for 24, 48 and 72 h, respectively, with P = 0.000. The creatinine level of the CIN group was higher than that of the MSCs group. After 72 h, histological evaluation of kidney sections from all rats was researched. However, proximal tubular vacuolization was signifi cantly less in rats pretreated with MSCs than in the CIN control rats. There was also signifi cantly difference in the levels of MDA, CAT, GSH-Px and T-SOD, which all favored the MSCs group. Conclusion The treatment of contr