光动力治疗联合托拉塞米对大鼠脑胶质瘤的影响研究  

Effects of photodynamic therapy combined with torasemide on rat glioma

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作  者:李波[1] 孟超[2] 鞠东辉 高万龙[5] 丛大忞 胡韶山 

机构地区:[1]连云港市第二人民医院神经外科,222000 [2]哈尔滨医科大学附属第二医院疼痛科,150086 [3]哈尔滨医科大学附属第四医院神经外科,150081 [4]沈阳市第十一人民医院神经外科,110033 [5]哈尔滨医科大学附属第二医院神经外科,150086

出  处:《国际生物医学工程杂志》2017年第5期346-352,共7页International Journal of Biomedical Engineering

基  金:国家自然科学基金(61575058);蚌埠医学院自然科学科研课题计划面上项目(BYKY16162);黑龙江省省院科技合作项目(YS14C11)

摘  要:目的 通过检测基质金属蛋白酶2(MMP2)、基质金属蛋白酶9(MMP9)、钠-钾-氯共转运体1(NKCC1)和血管内皮生长因子(VEGF)的表达,探讨光动力治疗(PDT)联合托拉塞米对大鼠脑胶质瘤的影响.方法 将确诊为脑胶质瘤的雄性Wistar大鼠随机分为对照组(Sham组)、光动力治疗组(PDT组)、托拉塞米组(T组)和光动力治疗联合托拉塞米组(PDT+T组),每组15只.Sham组大鼠不予任何处理;PDT组大鼠接受PDT(80 J/cm2) 10 min;T组大鼠仅腹腔注射托拉塞米(5 mg/kg),连续3 d;PDT+T组大鼠接受PDT后,再连续3d腹腔注射托拉塞米(5 mg/kg).2周后,每组取5只大鼠处死,取瘤周水肿组织检测湿干比(W/D),采用免疫组化、Western Blot和实时定量PCR法分别检测MMP2、MMP9、NKCC1和VEGF表达;剩余大鼠评估生存时间.结果 与Sham组相比,PDT组W/D(5.17±0.42比4.83±0.38)、NKCC1(0.54±0.21比0.35±0.12)和VEGF(0.68±0.20比0.42±0.15)蛋白表达升高,生存时间延长((32.2±2.9)d比(25.3±2.6)d),而MMP2(2.76±0.42比1.88±0.17)和MMP9(2.55±0.38比1.46±0.21)蛋白表达降低,差异均具有统计学意义(均P<0.05);与PDT组相比,T组W/D(3.68±1.04)、NKCC1 (0.22±0.10)和VEGF(0.33±0.14)蛋白表达降低,生存时间((28.7±2.2)d)缩短,MMP2(2.71±0.35)和MMP9 (2.42±0.36)蛋白表达升高,差异均具有统计学意义(均P<0.05);与PDT组相比,PDT+T组W/D (4.52±0.46)、NKCC1 (0.30±0.16)、VEGF(0.44±0.21)、MMP2(1.84±0.23)和MMP9(1.53±0.24)蛋白表达降低,生存时间((44.5±2.8)d)显著延长,差异均具有统计学意义(均P<0.05).结论 PDT联合托拉塞米可明显降低PDT诱发的瘤周水肿,降低肿瘤侵袭性,延长大鼠平均生存时间.Objective To study the effects of photodynamic therapy (PDT) combined with torasemide on rat glioma by detecting the protein expression of matrix metalloproteinase 2 (MMP2),matrix metalloproteinase 9 (MMP9),sodium-potassium-chloride co-transporter 1 (NKCC1) and vascular endothelial growth factor (VEGF).Methods Male Wistar rats with glioma were randomly divided into four groups,includes control group (sham group,n=15),photodynamic therapy group (PDT group,n=15),torasemide group (T group,n=15) and PDT+T group (n=15).The rats were normally fed in the sham group,were received PDT (80 J/cm2) for 10 min in the PDT group,were received intraperitoneal torasemide 5 mg/kg for 3 days in the T group,and received PDT and torasemide treatment in the PDT+T group.After 2 weeks,5 rats were sacrificed from each group.Peritumoral edema tissues were harvested for the detection of wet-dry-weight ratio (W/D),and the protein expression of MMP2,MMP9,NKCC 1 and VEGF by Western Blot,immunohistochemistry and qRT-PCR.The remaining rats were used for survival time assessment.Results Compared with the sham group,the PDT group showed an increase in W/D (5.17±0.42 vs 4.83±0.38),the expression of NKCC1 (0.54±0.21 vs 0.35±0.12) and VEGF (0.68±0.20 vs 0.42±0.15),and survival time ((32.2±2.9) d vs (25.3±2.6) d) (all P〈0.05),and showed an decrease in the expression of MMP2 (2.76±0.42 vs 1.88±0.17) and MMP9 (2.55±0.38 vs 1.46±0.21) (all P〈0.05).Compared with the PDT group,the T group showed decrease in W/D (3.68±1.04),the expression of NKCC1 (0.22±0.10) and VEGF (0.33±0.14),and survival time ((28.7±2.2) d) (all P〈0.05),and showed increase in the expression of MMP2 (2.71 ±0.35) and MMP9 (2.42±0.36) (all P〈0.05).Compared with the PDT group,the PDT+T group showed decrease in W/D (4.52±0.46),and the expression of NKCC1 (0.30±0.16),VEGF (0.44±0.21),MMP2 (1.84±0.23) and MMP9 (1.53±0.2

关 键 词:光动力治疗 托拉塞米 胶质瘤 

分 类 号:R739.4[医药卫生—肿瘤]

 

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