摘要
目的:探讨淫羊藿苷是否具有缓解缺血再灌注诱导急性肾损伤向慢性肾脏病转化的作用以及对PPAR信号通路的影响。方法:选用SPF级10周龄雄性C57BL/6小鼠随机分为3组,对照组(Control)、模型组(IRI)、模型+250 mg/kg淫羊藿苷组(IRI+I),每组6只,4周后小鼠处死,行病理染色,RT-PCR检测肾小管损伤和肾纤维化指标以及PPAR信号通路相关基因的变化。结果:Masson染色显示,IRI模型组肾间质纤维化严重,淫羊藿苷组与模型组相比肾间质纤维化程度明显改善(P<0.05),同时其肾损伤评分较模型组也有不同程度的改善(P<0.05);实时定量PCR显示,IRI组与Control组相比肾小管损伤、肾纤维化及炎症等基因Havcr-1、FN、Col3a1、TGF-β_(1)、TNF-α表达量均增加(P<0.05),IRI+I组与IRI组相比肾小管损伤、肾纤维化及炎症等基因Havcr-1、FN、Col3a1、TGF-β_(1)、TNF-α表达量显著减少(P<0.05);与对照组相比,模型组PparαmRNA、Cpt1a mRNA、Cpt2 mRNA、Acox2 mRNA水平显著下降,差异具有统计学意义(P<0.05);与模型组相比,淫羊藿苷组PparαmRNA、Cpt1a mRNA、Cpt2 mRNA、Acox2 mRNA水平显著上调,差异具有统计学意义。电镜观察到模型组线粒体结构损伤严重,线粒体肿胀变形,线粒体嵴断裂,淫羊藿苷组线粒体损伤程度较模型组减轻。结论:淫羊藿苷具有缓解缺血再灌注诱导急性肾损伤向慢性肾脏病转化,可能通过调节线粒体脂肪酸PPAR信号通路起到肾脏保护作用。
Objective:This study is aimed to explore the effect of icariin on retarding ischemia-reperfusion induced AKI to CKD transition and the effect on the PPAR signaling pathway.Methods:SPF 10-week-old male C57BL/6 mice were randomized into three groups:Control group(Control group),model group(IRI),and model+250 mg/kg icariin group(IRI+I),with six mice in each group.The mice were sacrificed four weeks later for pathological staining.RT-PCR was used to detect the changes of tubular injury,inflammatory,renal fibrosis,and PPAR signaling pathway-related genes.Results:Masson and H&E staining demonstrated that IRI model presented severe renal fibrosis with more collagen deposition and tubular injuries,while,icariin treatment attenuated renal fibrosis with less collagen deposition and tubular injuries.Real-time quantitative PCR showed the expression levels of tubular injury marker Havcr-1,inflammatory cytokine TNF-α,fibrotic marker FN,Col3a1,and TGF-β_(1)mRNA levels were increased in the IRI group compared with the Control group(P<0.05).The expression levels of tubular injury marker Havcr-1,inflammatory cytokine TNF-α,fibrotic markers FN,Col3a1,and TGF-β_(1)mRNA levels in the IRI+I group were significantly decreased compared with the IRI group(P<0.05).The mRNA levels of Ppara,Cpt1a,Cpt2,Acox2 in the model group were significantly decreased,and the differences were statistically significant(P<0.05).The mRNA levels of Pparα,Cpt1α,Cpt2,Acox2 in the icariin group were up-regulated with statistically significant differences.Electron microcopy showed icariin treatment rescued the IRI induced severe renal tubular mitochondria injuries characterized by enlarged and swelling mitochondria.Conclusion:Icariin attenuates ischemia-reperfusion induced AKI to CKD transition.Icariin may play a protective role in kidney by regulating mitochondria fatty acid PPAR signaling pathway.
作者
谢林
付莉莉
陈敏
梅长林
王怡
顾向晨
XIE Lin;FU Lili;CHEN Min(Department of Nephrology,Yueyang Hospital of Integrated Traditional And Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437)
出处
《中国中西医结合肾病杂志》
2022年第12期1047-1050,I0010,共5页
Chinese Journal of Integrated Traditional and Western Nephrology
基金
国家自然科学基金资助项目(No.81774106)
上海交通大学医学院“中西医结合研究”平台项目(No.2022ZXY003)。
