超声介导载阿霉素微泡对小鼠H22肝癌皮下移植瘤抑制作用的实验研究  

Inhibitory Effect of Ultrasound-mediated Doxorubicin-loaded Microbubbles on Subcutaneous H22 Hepatoma Transplantation in Mice

作　　者：罗小琴 刘朝奇[1] 邹云雷 杨饰琪 赵云[1] Luo Xiaoqin;Liu Zhaoqi;Zou Yunlei;Yang Shiqi;Zhao Yun(Medical College of China Three Gorges University,Yichang,Hubei 443000,China)

机构地区：[1]三峡大学医学院,湖北省宜昌市443000

出　　处：《中国超声医学杂志》2022年第1期111-115,共5页Chinese Journal of Ultrasound in Medicine

基　　金：国家自然科学基金项目(No.81473461);三峡大学学位论文培优基金项目资助(No.2021SSPY097)。

摘　　要：目的探讨超声介导载阿霉素微泡对小鼠H22肝癌皮下移植瘤的抑制效果。方法 (1)制备载阿霉素微泡,并检测其一般性质。(2)建立小鼠H22肝癌皮下移植瘤模型,将荷瘤小鼠随机分为对照组、空微泡+超声组、阿霉素组及阿霉素微泡+超声组,治疗5次后,绘制各组肿瘤生长曲线,计算抑瘤率,冰冻切片观察阿霉素在肿瘤组织的聚集情况,RT-PCR及免疫组化检测肿瘤组织中Bax、Bcl-2基因和蛋白的表达情况,Tunel检测肿瘤组织的细胞凋亡情况。结果 (1)制备的载阿霉素微泡呈球形,平均粒径为(438.33±12.87)nm,包封率为43.65%±3.84%。(2)阿霉素微泡+超声组肿瘤组织内阿霉素的聚集量是阿霉素组的3.49倍。与对照组相比,空微泡+超声组、阿霉素组及阿霉素微泡+超声组肿瘤生长均受到抑制,肿瘤体积和质量抑瘤率均升高,Bax基因和蛋白表达上调,Bcl-2基因和蛋白表达下调,肿瘤组织出现不同程度的细胞凋亡,上述结果以阿霉素微泡+超声组表现更明显(P<0.01)。结论超声介导载阿霉素微泡可抑制小鼠H22肝癌皮下移植瘤的生长,促进肿瘤细胞的凋亡。Objective To evaluate the inhibitory effect of ultrasound-mediated doxorubicin-loaded microbubbles on subcutaneous H22 hepatoma transplantation in mice. Methods(1)Microbubbles loaded with adriamycin were prepared and test their general properties were detected.(2)H22 hepatocellular carcinoma model in mice was established, and the tumor-bearing mice were randomly divided into control group, empty microbubbles + ultrasound group, doxorubicin group and doxorubicin microbubbles + ultrasound group. After 5 times of treatment, the tumor growth curve of each group was plotted and the tumor inhibition rate was calculated. The enrichment of doxorubicin in the tumor tissue was observed by frozen section. The expression of Bax and Bcl-2 genes and proteins in the tumor tissue were detected by RT-PCR and immunohistochemistry. Tunel was used to detect apoptosis in tumor tissues. Results(1)The prepared doxorubicin-loaded microbubbles were spherical, with an average particle size of(438.33±12.87) nm, and an encapsulation efficiency of 43.65%±3.84%.(2)The accumulation of doxorubicin in the tumor tissue of the Doxorubicin microbubbles + ultrasound group was 3.49 times that of the doxorubicin group. Compared with the control group, the tumor growth of the empty microbubbles+ultrasound group, the doxorubicin group and the doxorubicin microbubbles + ultrasound group was inhibited, the tumor volume and mass were increased, Bax gene and protein expression was up-regulated, Bcl-2 gene and protein expression was down-regulated, and tumor tissues have different degrees of apoptosis. The above results were more obvious in the doxorubicin microbubbles+ultrasound group(P<0.01). Conclusions Ultrasound-mediated doxorubicin-loaded microbubbles can inhibit the growth of subcutaneous transplanted H22 hepatoma in mice and promote apoptosis of tumor cell.

关 键 词：超声微泡 阿霉素 移植瘤 

分 类 号：R735.7[医药卫生—肿瘤]