尾加压素Ⅱ受体拮抗剂(urantide)减轻动脉粥样硬化大鼠肾脏损伤

UrotensinⅡreceptor antagonist(urantide)alleviates renal injury in rats with atherosclerosis

目的探讨尾加压素Ⅱ受体拮抗剂(urantide)减轻动脉粥样硬化(AS)肾损伤的作用机制。方法将大鼠分为正常组、模型组(连续3 d腹腔注射VitD 3150 U/(kg·d^(-1)),联合高脂特制饲料饲养,实验周期6周)、辛伐他汀组[5μg/(kg·d^(-1)),连续14 d]和干预模型组[urantide 30μg/(kg·d^(-1)),7 d和14 d]。组织形态学观察肾脏病理变化并评估损伤程度;RT-qPCR和免疫组化染色法检测基因和蛋白质表达。结果与正常组相比,模型组肾脏组织中肾小球萎缩且与周围组织黏连、肾小管上皮细胞水肿变性并伴有少量坏死,且肾小球和肾小管间质损伤评分升高(P<0.01);JAK2/STAT3基因和蛋白阳性表达升高(P<0.05,P<0.01),差异均有统计学意义。与模型组相比,urantide各组随用药时间的延长,肾脏组织病理变化明显改善,且肾小球硬化和肾小管间质损伤评分下降(P<0.01);JAK2/STAT3基因和蛋白阳性表达降低(P<0.05,P<0.01),差异均有统计学意义。结论Urantide可抑制JAK2/STAT3信号通路,为防治AS相关肾损伤开拓了新视野。

Objective To explore the mechanism of action of urantide in ameliorating renal injury caused by atherosclerosis(AS).Methods The rats were divided into normal group,model group which were treated with ip VitD3150 U/(kg·d^(-1))for 3 consecutive days,and fed with high-fat special diet,with an experimental period of 6 weeks,simvastatin group[5μg/(kg·d^(-1))for 14 consecutive days]and intervention model group[urantide 30μg/(kg·d^(-1)),7 d and 14 d].Microscopy was performed for observing pathological changes in the kidney and evaluation of the degree of renal tissue damage.RT-qPCR and immuno-histochemical staining microscopy was used to detect the expression of related genes and proteins.Results Compared to the normal group,the model group showed glomerular atrophy in the renal tissue and adhesion with surrounding tissues.The experiment found a series of changes in renal tubular epithelial cells,such as edema and degeneration,accompanied by a small area of cell necrosis.Sclerosis was found in the glomerulus;Increased positive expression of genes and proteins related to JAK2 and STAT3(P<0.05,P<0.01)was found.Compared to the model group,urantide groups with prolongated medicine administration and the pathological changes that occur in the kidney tissue showed obvious improvement and upturned.At the same time,the degree of glomerulosclerosis decreased and renal tubulointerstitial injury was improved(P<0.01);Positive expression of genes and proteins related to JAK2 and STAT3(P<0.05,P<0.01)all decreased.Conclusions Urantide may inhibit JAK2/STAT3 signal pathway and this finding may support the development of clinical strategy for the prevention and treatment of AS related renal injury.