实用医学杂志 ›› 2022, Vol. 38 ›› Issue (17): 2158-2164.doi: 10.3969/j.issn.1006⁃5725.2022.17.008

• 基础研究 • 上一篇    下一篇

超声激励bFGF纳米微泡靶向治疗对裸鼠瘢痕疙瘩及PTEN/PI3K/Akt 通路的影响

陈珂1 陈翠兰1 周雪萍1 任斯1 黄娟2    

  1. 1 武汉市第三医院超声科(武汉 430060);2 武汉市肺科医院功能科(武汉 430030)

  • 出版日期:2022-09-10 发布日期:2022-09-10
  • 通讯作者: 陈翠兰 E⁃mail:chen_chen00@126.com
  • 基金资助:
    武汉市医学科研项目(编号:WX19C24)

Effects of ultrasound ⁃ excited bFGF nano ⁃microbubble targeted therapy on keloids and PTEN/PI3K/Akt pathway in nude mice

CHEN Ke*,CHEN Cuilan,ZHOU Xueping,REN Si,HUANG Juan.   

  1. Ultrasonic Depart⁃ ment,Wuhan Third Hospital,Wuhan 430060,China 

  • Online:2022-09-10 Published:2022-09-10
  • Contact: CHEN Cuilan E⁃mail:chen_chen00@126.com

摘要:

目的 探讨超声激励碱性成纤维细胞生长因子(bFGF)纳米微泡靶向治疗对裸鼠瘢痕疙瘩 及第 10 号染色体同源缺失性磷酸酶⁃张力蛋白基因(PTEN)/3⁃磷酸肌醇激酶(PI3K)/丝氨酸⁃苏氨酸激酶 Akt)通路的影响。方法 构建裸鼠瘢痕疙瘩模型。将裸鼠分为对照组,bFGF 水溶液组,bFGF 纳米微泡 组,超声空化组,超声+bFGF 水溶液组,超声+bFGF 纳米微泡组,观察裸鼠生存状态和瘢痕疙瘩生长状 况。末次给药结束后次日取血,检测血清肿瘤坏死因子 α(TNF⁃α)、转化生长因子⁃β(TGF⁃β)水平;观察裸 鼠瘢痕疙瘩组织形态;检测瘢痕疙瘩组织细胞凋亡、瘢痕疙瘩组织中蛋白 caspase⁃3、α⁃SMA、collagen I PTEN、PI3K、Akt水平。结果 各bFGF处理组瘢痕疙瘩体积和重量、血清TNF⁃α、TGF⁃β水平、蛋白α⁃SMA collagen I、PI3K、Akt 均低于对照组,细胞凋亡数目、蛋白 caspase⁃3、PTEN 表达均高于对照组(P < 0.05);超 +bFGF 水溶液组、超声+bFGF 纳米微泡组瘢痕疙瘩体积和重量、血清 TNF⁃α、TGF⁃β 水平、蛋白 α⁃SMA collagen I、PI3K、Akt 均低于 bFGF 水溶液组、bFGF 纳米微泡组,细胞凋亡数目、蛋白 caspase⁃3、PTEN 表达均 高于 bFGF 水溶液组、bFGF 纳米微泡组(P < 0.05);超声+bFGF 纳米微泡对瘢痕疙瘩的抑制强于超声+bF⁃ GF 水溶液组(P < 0.05)。结论 超声激励 bFGF 纳米微泡能够抑制裸鼠瘢痕疙瘩的生长,可能与 PTEN/ PI3K/Akt 通路的激活有关。

关键词:

超声, 碱性成纤维细胞生长因子, 纳米微泡, 瘢痕疙瘩

Abstract:

Objective To investigate the effects of ultrasound ⁃ excited basic fibroblast growth factor (bFGF)nano⁃microbubble targeted therapy on keloids and phosphatase and tensin homolog deleted on chromosome ten(PTEN)/phosphatidylinositol 3⁃kinase(PI3K)/protein kinase B(Akt)pathway. Methods A nude mouse keloid model was constructed. The nude mice were divided into acontrol group,bFGF aqueous solution group,bFGF nano⁃ microbubble group,ultrasonic cavitation group,ultrasound plusbFGF aqueous solution group,and ultrasound plusbFGF nano⁃microbubble group. The survival status of nude mice and the growth of keloids were observed,and the volume and weight of keloids were measured. Blood was withdrawn the next day after the last administration and serum levels of tumor necrosis factor α(TNF⁃α)and transforming growth factor⁃ β(TGF⁃β)in nude mice were detected;the morphology of keloids in nude mice was observed;the apoptosis in keloid tissue was detected levels of protein caspase⁃3,α⁃SMA,collagen I,PTEN,PI3K,and Akt in keloid tissues were detected by Western blotting(WB). Results The volume and weight of keloids,serum TNF⁃αand TGF⁃β levels,protein α⁃SMA collagen I,PI3K,and Akt were lower in each bFGF treatment group thanin the control group,whilethe apoptosis count,protein caspase⁃3,andPTEN expression were higher(P < 0.05). The volume and weight of keloids,serum TNF ⁃ αand TGF ⁃ β levels,protein α ⁃ SMA,collagen I,PI3K,and Akt were lower in the ultrasound plusbFGF aqueous solution group and ultrasoundplusbFGF nano⁃microbubble group than in the bFGF aqueous solution group and bFGF nano⁃microbubble group,but the apoptosis count,protein caspase⁃3,and PTEN expression were higher (P < 0.05). Ultrasoundplus bFGF nano ⁃microbubbles was stronger than ultrasound plusbFGF aqueous solutioninsuppression of keloids(P < 0.05). Conclusions Ultrasound ⁃ excitedbFGF nano ⁃microbubbles can inhibit the growthof keloids,which may be related to the activation of the PTEN/PI3K/Akt pathway.

Key words: ultrasound,  , basic fibroblast growth factor,  , nano?microbubbles,  , keloids