前列环素对小鼠肾脏及血管系统发育的影响  

Effects of prostacyclin on the development of kidney and vascular system in mice

作　　者：曹映雪 郝传明 Cao Yingxue;Hao Chuanming(Division of Nephrology,Shenyang Fourth People′s Hospital,Shenyang 110000,China;Division of Nephrology,Huashan Hospital,Fudan University,Shanghai 200040,China)

机构地区：[1]沈阳市第四人民医院肾内科,沈阳110000 [2]复旦大学附属华山医院肾内科,上海200040

出　　处：《中华肾脏病杂志》2022年第10期899-904,共6页Chinese Journal of Nephrology

基　　金：沈阳市卫生健康委35岁以下青年医师承担项目(2020017)。

摘　　要：目的探讨前列环素(prostacyclin,PGI2)在小鼠肾脏及血管系统发育过程中的作用。方法构建C57BL/6J小鼠前列环素合成酶(prostacyclin synthase,PGIS)敲除模型,通过基因型鉴定观察PGIS敲除对小鼠存活率的影响;应用HE染色和PAS染色观察PGIS敲除对小鼠肾脏和血管系统发育的影响;观察PGIS敲除小鼠的肾脏大体形态;检测小鼠血尿素氮水平评估小鼠肾脏功能;应用实时荧光定量PCR分析PGIS敲除对前列腺素合成酶PGES和TXAS mRNA表达水平的影响;应用免疫荧光染色观察血管系统中PGIS的表达部位;采用尾套法测定小鼠的血压和心率。结果多数PGIS基因全身敲除纯合子(PGIS^(-/-))胎鼠在母鼠孕晚期死亡,个别PGIS^(-/-)胎鼠出生后可存活;PGIS^(-/-)胎鼠肾脏发育明显异常,表现为间质稀疏,组织分化异常,生肾囊泡延长,折叠形成的“S”形结构数量明显减少(P<0.01);存活的PGIS^(-/-)小鼠肾脏大体表现为组织萎缩、表面不规则和囊泡形成,血清尿素氮水平显著高于野生型(PGIS^(+/+))小鼠[(36.89±5.39)mmol/L比(5.07±0.69)mmol/L,n=3,P<0.01]。PGIS^(+/+)小鼠和PGIS^(-/-)小鼠PGES和TXAS mRNA表达的差异无统计学意义。免疫荧光结果显示PGIS广泛表达于PGIS^(+/+)小鼠肾脏血管内皮细胞和平滑肌细胞;光镜下可以观察到PGIS基因全身敲除杂合子(PGIS+/-)小鼠肾脏血管平滑肌层缺失、内皮下疏松层增宽、血管壁变薄、内弹力板不连续等多种形态异常;PGIS+/-和PGIS^(+/+)小鼠血压和心率的差异无统计学意义。结论PGIS在小鼠肾脏及血管系统发育中起重要作用。Objective To explore the role of prostacyclin(PGI2)in the development of kidney and vascular system in mice.Methods The prostacyclin synthase(PGIS)knockout model was established in C57BL/6J mice.The effects of PGIS knockout on the survival rate of mice were observed by genotyping analysis.The effects of PGIS knockout on the development of kidney and vascular system in mice were observed by hematoxylin and eosin staining and periodic acid-Schiff staining.The morphological changes of kidneys in PGIS knockout mice were observed.Blood urea nitrogen was tested to evaluate the function of kidney in mice.Real-time quantitative PCR was used to analyze the effect of PGIS knockout on the mRNA expression of prostaglandin synthetase PGES and TXAS.The expression of PGIS in vascular system was observed by immunofluorescence staining.The blood pressure and heart rate of mice were measured by the tail-cuff method.Results Most of the systemic complete PGIS knockout(PGIS^(-/-))fetal mice sacrificed.The kidneys of PGIS^(-/-)fetal mice developed abnormally,which showed sparse interstitial,abnormal tissue differentiation,lengthened renal vesicle,and significant decrease in the number of“S”-shape bodies(P<0.01).The kidneys of PGIS^(-/-)mice showed tissue atrophy,surface irregularities and cyst formation.Blood urea nitrogen level in the PGIS^(-/-)mice was significantly higher than that in the wild type(PGIS^(+/+))mice[(36.89±5.39)mmol/L vs(5.07±0.69)mmol/L,n=3,P<0.01].There was no significant difference in the mRNA expression of PGES and TXAS between PGIS^(+/+)mice and PGIS^(-/-)mice.PGIS was widely expressed in renal vascular endothelial cells and smooth muscle cells of PGIS^(+/+)mice.Vascular system developed abnormally,which showed loss of smooth muscle layer,width of subendothelial loose layer,thinning of the pipe wall,and discontinuity of the inner elastic plate in PGIS+/-mice.There was no significant difference in the blood pressure and heart rate between PGIS systemic half-knockout(PGIS+/-)mice and PGIS^(-/-)mice.Conclusio

关 键 词：前列腺素 肾 心血管系统 前列环素 发育 

分 类 号：R692[医药卫生—泌尿科学]