QDPR通过调控Beclin1改善UUO诱导的大鼠肾间质纤维化  

QDPR improves UUO-induced renal interstitial fibrosis in rats by regulating Beclin1

作　　者：高海洋 何海兰 张立国 陈曦 李治国 Gao Haiyang;He Hailan;Zhang Liguo;Chen Xi;Li Zhiguo(Dept of Urology,Affiliated Hospital of North China University of Science and Technology,Tangshan 063210;School of Public Health,North China University of Science and Technology,Tangshan 063210)

机构地区：[1]华北理工大学附属医院泌尿外科,唐山063210 [2]华北理工大学公共卫生学院,唐山063210

出　　处：《安徽医科大学学报》2023年第5期806-811,共6页Acta Universitatis Medicinalis Anhui

基　　金：河北省自然科学基金(编号:H2020209243);河北省医学科学研究课题计划(编号:20210159)。

摘　　要：目的探讨醌型二氢生物喋呤还原酶(QDPR)在单侧输尿管梗阻(UUO)大鼠模型肾间质纤维化中的作用及对Beclin1的影响。方法通过单侧输尿管结扎的方法构建UUO模型,Masson、COLⅠ染色和Western blot技术分析纤维化进展及QDPR和Beclin1的表达情况。慢病毒输尿管逆行注射构建过表达QDPR基因和空载对照UUO模型,评估慢病毒感染效率和QDPR表达情况,并检测QDPR过表达对纤维化进展和Beclin1表达的影响。结果UUO模型组较假手术组的胶原纤维表达水平增高(P<0.05),QDPR表达水平降低(P<0.05),Beclin1表达增高(P<0.05)。通过输尿管逆行注射慢病毒,成功感染肾脏,并能增加肾脏QDPR表达。过表达QDPR后,胶原纤维表达水平降低(P<0.05),且Beclin1表达水平下降(P<0.05)。结论过表达QDPR抑制了Beclin1的表达水平,改善了纤维化的进展,提示过表达QDPR可能通过抑制Beclin1进而抑制肾间质纤维化。Objective To investigate the effect of QDPR on renal interstitial fibrosis and Beclin1 expression of unilateral ureteral obstruction(UUO)rat model.Methods The UUO model was constructed by unilateral ureteral ligation.The fibrosis progression,QDPR and Beclin1 expression of UUO model were evaluated by Masson,COLⅠstaining and Western blot techniques.UUO model which was over expression QDPR and its control were constructed by retrograde ureteral infusion of corresponding lentivirus.Infection efficiency and QDPR expression level were further evaluated.The QDPR overexpression on fibrosis progression,and Beclin1 was further analyzed.Results Compared with the sham operation group,the collagen fibers level in the UUO model group significantly increased(P<0.05),the QDPR expression level was significantly reduced(P<0.05),and the Beclin1 significantly increased(P<0.05).Retrograde injection of lentivirus through the ureter could successfully infect the kidney and increase the expression level of QDPR in the kidney.The overexpression of QDPR in kidney could significantly decrease collagen fibers(P<0.05)and Beclin1(P<0.05)expression.Conclusion Overexpression of QDPR inhibits the expression level of Beclin1 and progression of fibrosis,suggesting that overexpression of QDPR may relieve renal interstitial fibrosis by inhibiting Beclin1expression.

关 键 词：醌型二氢生物喋呤还原酶 BECLIN1 肾间质纤维化 

分 类 号：R364.24[医药卫生—病理学]