摘要
目的观察Intermedin(IMD)预处理对大鼠肾脏缺血再灌注损伤(IRI)修复过程中细胞周期蛋白(cyclin)D1、cyclinE以及其依赖性激酶(CDKs)表达的影响,从而探讨IMD在这一过程中促进肾组织再生修复的作用机制。方法健康雄性Wistar大鼠共144只,体质量180-220g,随机分为对照组、IRI组、转空质粒组、转IMD组,每组36只。IRI组切除右肾后钝性分离左侧腹主动脉及肾动脉;转空质粒组、转IMD组大鼠切除右肾后,在六氟化硫微泡(声诺维)介导下将空质粒及IMD质粒转染入左肾;1周后分别制作肾脏IRI模型。每组于再灌注第1、2、3、4、7、14天时各取6只留取肾组织标本。检测各组肾组织中cyclinD1与CDK4,cyclinE与CDK2的表达。统计学处理采用单因素方差分析和t检验。结果IRI组cyclinD1、cyclinE以及CDK4.CDK2于再灌注后第1、2、3、4、7天表达逐渐增高,第7天时到达最高峰,第14天时仍有少量表达,与对照组比较差异有统计学意义(F值=54.92,69.60,61.28,77.38,P均〈0.05)。转IMD组上述指标在第1天即开始显著增高,第2、3、4、7天呈进行性下降,至第14天时恢复正常,与IRI组相比差异具有统计学意义(F值=54.92,69.60,61.28,77.38,P均〈0.05);转空质粒组与IRI组以上指标差异无统计学意义。结论IMD预处理在大鼠肾脏缺血再灌注损伤后早期能使cvclinDl、cyclinE以及CDK4、CDK2的表达明显上调,这一机制可能促进细胞周期进展从而加快肾组织再生修复。
Objective To observe the effect of intermedin (IMD) preconditioning on cyclin D1, cyclin E and CDKs expression, and explore its role in promoting kidney tissue regeneration after renal ischemia- reperfusion injury. Methods One hundred and forty-four healthy male Wistar rats were randomly divided into four groups: sham operation (S) group, ischemia-reperfusion injury (IR) group, empty plasmid (EP) group and IMD group. In the IR group, after the right kidney was excised, the aorta abdominalis and left renal artery were bluntly dissected in EP and IMD group, empty plasmid and IMD plasmid were transfected into the left kidney using ultrasound-micro-bubble (SonoVue) mediated system, respectively. One week later, renal IRI model was made by clasping the left renal artery for 45 min. After 1, 2, 3, 4, 7 and 14 day of reperfusion, the kidney in each group was collected to detect the expression of cyclin D1, cyclin E, CDK4 and CDK2 by western blot analysis or enzyme-linked immunosorbent assay (ELISA). Results Compared with S group, the expression of cyclin D1, cyclin E, CDK4 and CDK2 was significantly up-regulated in day 1, 2, 3, 4, 7 and 14 in IR group. And the above index increased gradually after repeffusion, and reached the peak at day 7 (F=54.92, 69.60, 51.28, 77.38, P〈0.05). While in IMD group, these indexes reached the peak at day 1, then progressively declined, and could not be detected at day 14 (compared with the IR group, F= 54.92, 69.60, 61.28, 77.38, P〈0.05). Conclusion IMD preconditioning can up-regulate the expression of cyclin D1, cyclin E, CDK2 and CDK4 in the early phase of renal ischemia-reperfusion injury that may accelerate repair of renal tissue, at least by, part~ by enhancinge cell proliferation.
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2011年第8期541-545,共5页
Chinese Journal of Rheumatology
基金
基金项目:国家自然科学基金(30971380)
山西省农社科技攻关项目(20080311061-6)