阿霉素肾病大鼠肾组织NF-κB表达及甘草甜素的防护作用

Study on the expression of nuclear factor-κB in nephridial tissue and the protective role of glycyrrhizin on adriamycin nephropathy in rats

目的观察甘草甜素对阿霉素肾病大鼠肾组织中核因子-κB(NF-κB)表达的影响,探讨甘草甜素对阿霉素肾病大鼠的防护作用。方法18只SD雄性大鼠随机分为3组:A组(正常对照组)、B组(模型组)、C组(甘草甜素治疗组)每组6只。模型组和甘草甜素治疗组大鼠采用尾静脉注射阿霉素的方法建立阿霉素肾病模型。甘草甜素治疗组予以甘草甜素灌胃6周,正常对照组和模型组大鼠予以等量生理盐水灌胃。检测各组大鼠24h尿蛋白定量及血清生化指标。观察各组大鼠肾组织病理学改变,检测肾组织中核因子-κB(NF-κB)活性及其下游炎症因子结缔组织生长因子(connective tissue growth factor,CTGF)的表达水平。结果甘草甜素治疗组于用药第6周24h尿蛋白定量与同期模型组相比,均有明显改善,差异有统计学意义。甘草甜素治疗组大鼠肾组织病理学改变明显优于模型组,且肾组织中NF-κB活性、CTGF水平也明显下降,差异有统计学意义。结论甘草甜素可能直接或间接抑制肾组织中NF-κB活化,减轻肾小球细胞外基质的积聚,从而延缓肾小球硬化的进程。

Objective To observe the effects of glycyrrhizin on nuclear factor-κB（NF- κB） expression in kidney tissue of rats with adriamycin nephropathy, and to explore the protective effect s of glycyrrhizin on glomerulosclerosis. Methods Eighteen SD rats were randomly divided into 3 groups： normal control group （n=6）, untreated group （n=6） and glycyrrhizin treated group （n=6）. Adriamycin nephropathy was induced in rats in the last two groups by intravenous injection of adriamycin. The rats in the glycyrrhizin treated group were fed glycyrrhizin for six weeks, whereas the rats in the normal control group and untreated group were fed normal saline solution for six weeks. The levels of 24h urine protein （Upr）, serum creatinine （Cr）, urea nitrogen （BUN）, albumin （Alb） and cholesterol （Ch） of the rats in each group were examined before and after treatment for six weeks. The renal morphological changes were observed under microscope. The NF-κB activity in renal tissue was measured by electrophoretic mobility shift assays （EMSA） and the expression level of CTGF in renal tissue was detected by streptavidin biotin peroxidase complex （SABC） method. Results The levels of 24 h Upr after the treatment for eight weeks in the glycyrrhizin treated group were both significantly decreased as compared with those in the untreated group. The pathological morphological changes of renal tissue in the glycyrrhizin treated group were remarkably alleviated , The NF-κB activity and CTGF level in renal tissue were also decreased in the glycyrrhizin treated group as compared with those in the untreated group. Conclusion The glycyrrhizin can exert certain protective effects on adriamycin nephropathy in rats by inhibiting NF-κB activity so as to retardthe development of glomerulosclerosis.