目的在“骨肉不相亲”理论指导下,比较废用性骨质疏松症大鼠股骨、腓肠肌中果蝇母本抗生存因子蛋白2/3(small mother against decapentaplegic 2/3,Smad2/3)、特异性蛋白1(specificity protein 1,SP1)表达在中医不同治法下的影响,分析...目的在“骨肉不相亲”理论指导下,比较废用性骨质疏松症大鼠股骨、腓肠肌中果蝇母本抗生存因子蛋白2/3(small mother against decapentaplegic 2/3,Smad2/3)、特异性蛋白1(specificity protein 1,SP1)表达在中医不同治法下的影响,分析中医药对其的防治机制。方法将60只大鼠随机分为正常组、模型组、补肾组、健脾组、补肾健脾组、西药组6组,并适应性喂养1周,造模组采用尾吊法建立模型,5周后取大鼠的腹主动脉血清、股骨及腓肠肌。通过骨密度检测和对股骨远端横断面处的骨形态进行三维重建观察比较各组大鼠股骨组织结构变化,评估骨质流失情况。采用HE染色和Masson染色观察大鼠腓肠肌组织的形态学变化。采用ELISA法检测各组大鼠血清碱性磷酸酶(alkaline phosphatase,ALP)、抗酒石酸酸性磷酸酶(tartrate resistant acid phosphatase,TRACP)水平和股骨、腓肠肌中Smad2/3、SP1蛋白表达。结果与正常组比较,模型组大鼠股骨骨密度显著降低(P<0.01),骨微结构破坏明显;腓肠肌肌纤维萎缩,排列疏松;血清ALP水平显著降低、TRACP水平显著升高(P<0.01);股骨与腓肠肌中Smad2/3、SP1蛋白表达显著升高(P<0.01)。与模型组比较,各给药组股骨骨密度明显升高(P<0.05),骨微结构修复明显;腓肠肌肌纤维增粗,肌间隙减小;ALP水平明显升高(P<0.05,P<0.01)。与模型组比较,补肾健脾组和西药组TRACP水平降低最显著(P<0.01),其次是补肾组(P<0.05);各给药组股骨与腓肠肌中Smad2/3、SP1蛋白表达显著降低(P<0.01)。结论废用性骨质疏松症的发生、发展可能与骨骼及肌肉中Smad2/3、SP1蛋白表达的升高有关,二者的高表达可能会导致骨-肌失衡。各中医治法对废用性骨质疏松症的防治作用可能与降低骨骼与肌肉中Smad2/3、SP1蛋白表达有关。展开更多
Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the ci...Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied.Methods:Western blot,immunohistochemistry,and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression.The CCK-8 assay was used to assess cell growth.The Transwell assay was used to detect invasion and migration of cells.The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4(or SP1)bind to one another.An in vivo assay was used to measure tumor growth.Results:It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues.CircPDIA4 knockdown prevented the invasion,migration,and proliferation of cells in CRC.Additionally,the combination of circPDIA4 and miR-9-5p was confirmed,as well as miR-9-5p binding to SP1.Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC.In addition,SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription.CircPDIA4 was shown to facilitate tumor growth in an in vivo assay.Conclusions:The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression.This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82073276 and 82273100)Science and Technology Project of Tianjin Binhai New Area Health Commission(Grant No.2022BWKY016)the China Digestive Tumor Clinical Scientific Research Public Welfare Project(Grant No.P014-058).
文摘Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied.Methods:Western blot,immunohistochemistry,and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression.The CCK-8 assay was used to assess cell growth.The Transwell assay was used to detect invasion and migration of cells.The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4(or SP1)bind to one another.An in vivo assay was used to measure tumor growth.Results:It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues.CircPDIA4 knockdown prevented the invasion,migration,and proliferation of cells in CRC.Additionally,the combination of circPDIA4 and miR-9-5p was confirmed,as well as miR-9-5p binding to SP1.Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC.In addition,SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription.CircPDIA4 was shown to facilitate tumor growth in an in vivo assay.Conclusions:The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression.This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.
