rhBMP-2对肾缺血再灌注损伤大鼠肾组织的影响及其分子机制

Influence of rhBMP-2 on the renal tissue of rat with renal ischemia reperfusion injury and its molecular mechanism

探讨重组人骨形成蛋白-2(bone morphogenetic protein2,BMP-2)对肾缺血再灌注损伤(ischemia reperfusion injury,IRI)大鼠肾组织的影响。研究复制了大鼠肾IRI模型,并将Wistar大鼠随机分为假手术(S)组、肾IRI模型(R)组以及rhBMP-2预处理(于术前给予不同剂量rhBMP-2)组(B组),观察肾组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)的含量,SOD活性、MDA含量,BUN、Scr含量以及肾功能和结构的变化。结果表明,与肾IRI模型组相比,rhBMP-2能显著降低肾组织中IL-6和IL-8的含量(P<0.05),rhBMP-2(4μg·kg-1)能显著降低肾组织中的TNF-α含量(P<0.05);亦能显著降低血浆中的BUN、Scr含量,增强肾组织中的SOD活性、降低肾组织中的MDA含量,使肾IRI大鼠的肾损害得到明显改善。与肾IRI模型组相比,rhBMP-2能显著减轻肾缺血再灌注损伤后肾组织结构的病变情况。由此可以推断,rhBMP-2可通过抑制肾组织促炎症细胞因子产生及抗氧化作用而减轻肾缺血再灌注损伤。

The objective of this research is to investigate the influence of rhBMP-2 on the renal tissue of rat with renal ischemia reperfusion injury.In this program the ischemia reperfusion rat model was established and Wistar rats were divided into six groups：sham operation group（S group）,renal ischemia reperfusion injury group（R group）,rhBMP-2 treatment group（B1,B2,B3 and B4 group）.In the rhBMP treatment groups,rhBMP-2 was intravenously administered with different doses before reperfusion.The contents of TNF-α,IL-6,IL-8,MDA and SOD in kidney tissue were observed.At the same time,renal function（blood creatine（Scr） and urea nitrogen（BUN）） were measured.As a result,compared with renal ischemia reperfusion group,administration of rhBMP-2 significantly reduced the content of IL-6 and IL-8（P 〈 0.05） and ameliorated renal dysfunction cellular damages（P 〈 0.05）.Higher dose of rhBMP-2 may reduce the content of TNF-α（P 〈 0.05） in kidney tissue.rhBMP-2 also increased activity of SOD and reduced the level of MDA,BUN and Scr.So,we can draw a conclusion that rhBMP-2 treatment attenuates renal ischemia reperfusion injury through inhibition of pro-inflammatory cytokines production and anti-oxidation activity.