摘要
目的探讨全反式维甲酸(ATRA)对大鼠肾间质纤维化(RIF)的延缓作用及其可能分子机制。方法将36只大鼠随机分为ATRA组、RIF模型组和假手术组,每组12只。ATRA组、RIF模型组大鼠采用左侧输尿管梗阻方法建立RIF模型,假手术组只开腹探及肾包膜。术前1 d,ATRA组给予ATRA灌胃,其余2组灌胃等量生理盐水。于造模后的第2周末和第4周末,每组随机抽取6只大鼠。留取大鼠左侧肾组织,行Masson染色并计算RIF指数,免疫组织化学法检测肾组织维甲酸受体α(RARα)、阻抑素、Ⅳ型胶原蛋白(ColⅣ)、纤维连接蛋白(FN)的表达水平,实时荧光定量PCR检测肾脏组织RARα、阻抑素的mRNA表达水平。结果造模后的第2周末和第4周末,假手术组、ATRA组、RIF模型组RIF指数、ColⅣ和FN的蛋白表达水平依次升高,RARα和阻抑素的蛋白、mRNA表达水平依次降低(均P<0.05);在ATRA组、RIF模型组,与第2周末比较,第4周末RIF指数、ColⅣ和FN的蛋白表达水平更高,而RARα和阻抑素的蛋白、mRNA表达水平更低(均P<0.05)。在RIF模型组中,第2、4周末时,RARα蛋白表达水平与阻抑素蛋白表达水平均呈正相关,与RIF指数、ColⅣ和FN蛋白表达水平均呈负相关(均P<0.05)。结论ATRA具有延缓大鼠RIF的作用,其可能通过上调肾脏组织RARα表达,调控阻抑素的表达,从而发挥作用。
Objective To investigate the inhibitory effect of all-trans retinoic acid(ATRA)on progression of renal interstitial fibrosis(RIF)in rats and its possible molecular mechanism.Methods Thirty-six rats were randomized to ATRA group,RIF model group or sham operation group,with 12 rats in each group.The RIF model was established by using left ureteral obstruction method in the ATRA group and the RIF model group,whereas open renal capsule exploration was performed in the sham operation group.One day before operation,the ATRA group was given intragastric administration of ATRA,and the remaining two groups were given intragastric administration of equivalent normal saline.At the end of the second and fourth weeks after modeling,6 rats were randomly selected from each group.After collecting the left kidney tissues of the rats,Masson staining was performed and RIF index was calculated,immunohistochemistry assay was employed to determine the expression levels of retinoic acid receptor alpha(RARα),prohibitin,typeⅣcollagen(ColⅣ)and fibronectin(FN)proteins in kidney tissues,and real-time fluorescent quantitative PCR was applied to detecting the expression levels of RARαand prohibitin mRNAs in kidney tissues.Results At the end of the second and fourth weeks after modeling,RIF index,the expression levels of ColⅣand FN proteins increased,whereas the protein and mRNA expression levels of RARαand prohibitin declined in the order of the sham operation group,the ATRA group and the RIF model group(all P<0.05);the ATRA group and the RIF model group obtained higher RIF index,higher expression levels of ColⅣand FN proteins,as well as lower protein and mRNA expression levels of RARαand prohibitin at the end of the fourth week than at the end of the second week(all P<0.05).In the RIF model group,at the end of the second or fourth week,the expression level of RARαprotein positively correlated with the expression level of prohibitin protein,but negatively correlated with RIF index and the expression levels of ColⅣand FN protein
作者
周添标
钟红珍
钟志青
谢伟基
翁文娟
ZHOU Tian-biao;ZHONG Hong-zhen;ZHONG Zhi-qing;XIE Wei-ji;WENG Wen-juan(Department of Nephrology,the Second Affiliated Hospital of Shantou University Medical College,Shantou 515041,China)
出处
《广西医学》
CAS
2020年第7期830-834,共5页
Guangxi Medical Journal
基金
广东省自然科学基金(2015A030310386)
广东省医学科学技术研究基金项目(A2018336)
广东省汕头市医疗卫生科技计划项目(汕府科[2019]106号4)。
关键词
肾间质纤维化
全反式维甲酸
维甲酸受体Α
阻抑素
Ⅳ型胶原
纤维连接蛋白
大鼠
Renal interstitial fibrosis
All-trans retinoic acid
Retinoic acid receptor alpha
Prohibitin
TypeⅣcollagen
Fibronectin
Rat
