大黄素对骨髓间充质干细胞移植治疗缺血性再灌注肾损伤的影响  

Emodin effects on renal ischemia/reperfusion injury after bone marrow mesenchymal stem cell transplantation

作　　者：李忠[1] 

机构地区：[1]南阳理工学院张仲景国医学院,河南省南阳市473004

出　　处：《中国组织工程研究》2016年第14期2052-2058,共7页Chinese Journal of Tissue Engineering Research

摘　　要：背景:已有研究表明大黄素通过抑制炎症因子释放对肠缺血再灌注损伤具有保护作用。目的:探讨大黄素对骨髓间充质干细胞移植治疗缺血性再灌注肾损伤的作用。方法:40只SD大鼠随机分为5组(n=8):假手术组、缺血再灌注组、骨髓间充质干细胞组、大黄素低剂量干预组、大黄素高剂量干预组。除假手术组外,其余4组建立大鼠肾缺血再灌注损伤模型。造模后骨髓间充质干细胞组下腔静脉注射1 mL骨髓间充质干细胞悬液,大黄素低剂量干预组与高剂量干预组术前7 d内每天灌胃大黄素30 mg/kg和60 mg/kg,后续处理与骨髓间充质干细胞组一致。再灌注6 h后,苏木精-伊红染色法检测肾组织病理改变,实时荧光定量PCR检测肿瘤坏死因子α,白细胞介素6和白细胞介素18以及TLR2和TLR4 mR NA表达水平,免疫印迹法检测COX-2,ICAM-1,i NOS蛋白表达水平。结果与结论:(1)缺血再灌注后可见大量小管上皮脱落,间质有炎性细胞浸润;骨髓间充质干细胞组可见部分小管上皮细胞脱落,部分间质有炎细胞浸润;药物低剂量干预组与高剂量干预组肾小管管腔几乎完整,少量间质有炎细胞浸润;(2)与假手术组相比,缺血再灌注组肿瘤坏死因子α,白细胞介素6,白细胞介素18以及TLR2,TLR4 m RNA表达水平显著升高(P<0.05),COX-2,ICAM-1,iN OS蛋白表达水平也显著升高(P<0.05);骨髓间充质干细胞组上述各因子表达明显低于缺血再灌注组(P<0.05);大黄素低剂量干预组与高剂量干预组的降低程度更为显著,且与大黄素剂量相关;(3)结果表明,大黄素具有促进骨髓间充质干细胞改善大鼠缺血性再灌注肾损伤的作用。BACKGROUND： Studies have shown that emodin protects against intestinal ischemia-reperfusion injury by inhibiting the release of inflammatory factors.OBJECTIVE： To investigate the effect of emodin on renal ischemia/reperfusion injury after bone marrow mesenchymal stem cell transplantation. METHODS： Forty Sprague-Dawley rats were randomized into five groups（n=8 per group）： sham group, model group（renal ischemia/reperfusion injury group）, bone marrow mesenchymal stem cell group（cell transplantation group）, low-dose emodin group, high-dose emodin group. Rats in the latter four groups were pretreated with or without different concentrations（30 and 60 mg/kg） of emodin for 7 days, and then were subjected to clamping bilateral renal pedicles for 45 minutes, followed by injection of 1 mL bone marrow mesenchymal stem cell suspension. Six hours after reperfusion, the pathological changes of renal tissues were examined by hematoxylin-eosin staining; the mR NA levels of tumor necrosis factor α, interleukin-6, interleukin-18, TLR2 and TLR4 detected by real-time fluorescence quantitative PCR; and the protein expression of COX-2, ICAM-1 and i NOS determined by western blot. RESULTS AND CONCLUSION： Compared with the sham group, rats in the model group showed obvious features of severe acute tubular damage and inflammatory cell infiltration. In the cell transplantation group, tubular epitheliael cells were partially lost with some inflammatory cells infiltrated in the renal interstitium. In the emodin groups, the tubular lumen was practically intact with little renal interstitial inflammatory cells. Compared with the sham group, a significant increase in the mR NA levels of tumor necrosis factor α, interleukin-6, interleukin-18, TLR2 and TLR4 as well as in the protein levels of COX-2, ICAM-1 and i NOS was found in the model group（both P〈 0.05）. However, bone marrow mesenchymal stem cell transplantation attenuated this ischemia/reperfusion-induced increase in the expression of the above-mentioned f

关 键 词：骨髓 间质干细胞移植 再灌注损伤 肾 大黄素 组织工程 干细胞 移植 骨髓间充质干细胞 缺血性再灌注肾损伤 肿瘤坏死因子α 白细胞介素6 白细胞介素18 TLR2 TLR4 COX-2 ICAM-1 INOS 

分 类 号：R394.2[医药卫生—医学遗传学]