目的 通过研究微泡超声空化增强微波消融对兔VX2肿瘤的热消融效应来探究其在肿瘤治疗中的价值。方法 24只肝脏移植瘤兔随机分为空白对照组、单纯超声空化治疗组、单纯微波消融治疗组、超声空化联合微波消融治疗组4组。利用增强超声显示每组治疗前后肿瘤的大小、形状和轮廓并通过温度针来检测治疗区域的局部温度。结果 联合治疗组血流灌注缺损最严重,微波消融组和联合治疗组缺损体积分别为1.53±0.20和1.68±0.43(P=0.117);微波消融组以及联合治疗组消融治疗时温度达平台时间分别为(21.7±5.0)s和(10.3±5.0)s(P<0.01),最高温度(℃)分别为100.9±5.0和134.1±6.0(P<0.01)。结论 MWA联合MEUS治疗肝癌可使治疗区局部温度急剧升高至峰值温度,有望提高肝癌治疗效果。

Objective To investigate the thermal ablation effect of microbubble ultrasound cavitation combined with microwave ablation on rabbit VX2 tumors. Methods Twenty-four rabbits with liver transplantation tumors were randomly divided into four groups: blank control group, ultrasound-only cavitation treatment group, microwave-only ablation treatment group, and ultrasound-cavitation combined with microwave ablation treatment group. Enhanced ultrasound was used to show the size, shape and contour of the tumor before and after treatment in each group, and the local temperature of the treatment area was detected by a temperature needle. Results The blood flow perfusion defect was the most severe in the combined treatment group. The defect volume of the microwave ablation group and the combined treatment group were 1.53±0.20 and 1.68±0.43 (P=0.117). The temperature reached the plateau time in the microwave ablation group and the combined treatment group. It was (21.7±5.0)s and (10.3±5.0)s (P<0.01), and the highest temperature (℃) was 100.9±5.0 and 134.1±6.0 (P<0.01). Conclusion MWA combined with MEUS for liver cancer can sharply increase the local temperature in the treatment area to the peak temperature, which is expected to improve the treatment effect of liver cancer.

目的 探讨低机械指数诊断超声及低声压治疗超声对造影剂微泡的作用效果。方法 低机械指数的诊断超声及不同声压下低能量治疗超声体外辐照造影剂微泡,通过获得的超声造影图像间接分析微泡总浓度的变化,探讨不同机械指数诊断超声及不同声压治疗超声下微泡发生稳定空化及惯性空化情况。结果 低机械指数(<0.2)诊断超声及低声压(<0.15 MPa)治疗超声下微泡以稳定空化为主,随着机械指数增高或声压增高,微泡以稳定空化和惯性空化两种方式并存,当机械指数>0.3或声压>0.2 Mpa时,微泡以惯性空化为主。结论 微泡在低机械指数及低声压作用下发生不同空化效应,随着机械指数或声压增加,微泡破坏增加,以惯性空化效应为主。

Objective To investigate the effect of low mechanical index diagnostic ultrasound and low acoustic pressure therapy on contrast agent microbubbles. Methods Microbubbles were irradiated by diagnostic ultrasound with low mechanical index(MI) and low energy therapy under different acoustic pressure. To obtain the images, and analyze the change of microbubble concentration,the movement trend of microbubbles under different MI and different acoustic pressure were analyzed, to estimated stable cavitation or inertial cavitation of microbubbles. Results Stable cavitation was the main form of microbubbles under low mechanical index (< 0.2) diagnostic ultrasound and low acoustic pressure (< 0.15Mpa). With the increase of mechanical index or acoustic pressure, stable cavitation and inertial cavitation coexisted. When mechanical index > 0.3 or sound pressure > 0.2MPa, microbubbles were mainly inertial cavitation. Conclusion The cavitation effects of microbubbles under low mechanical index and low acoustic pressure are different. With the increase of mechanical index or acoustic pressure, the damage of microbubbles increases, and main effect is the inertial cavitation.

目的 探究超声-微泡介导的miR-128通过调节PTEN对乳腺癌细胞阿霉素耐药的影响。方法 qPCR检测miR-128在乳腺癌细胞系中的表达,并利用结合微泡的miR-128质粒(质粒+超声+SF6微泡)转染细胞,探究超声-微泡介导的miR-128对乳腺癌细胞阿霉素耐药的影响。CCK8实验检测乳腺癌细胞的活性;qPCR检测过表达miR-128后对PTEN的影响和对乳腺癌细胞阿霉素耐药的影响。结果 miR-128在阿霉素耐药乳腺癌细胞中低表达;过表达miR-128能够增加乳腺癌细胞对阿霉素的敏感性,超声-微泡介导的miR-128进一步增强了乳腺癌细胞对阿霉素的敏感性;miR-128通过调节PTEN从而促进乳腺癌细胞对阿霉素耐药。结论 miR-128过表达可以增强乳腺癌对阿霉素的敏感性,超声-微泡介导的miR-128进一步增强了乳腺癌细胞对阿霉素的敏感性,本研究为乳腺癌阿霉素耐药的治疗提供了新的分子靶标和治疗途径。

Objective To explore the effect of ultrasound-microbubble mediated miR-128 on doxorubicin resistance in breast cancer cells by regulating PTEN. Methods Quantitatine PCR (qPCR) was used to detect the expression of miR-128 in breast cancer cell lines, and the ultrasound-microbubble combined miR-128 plasmid(plasmid+ultrasound+SF6 microbubbles) was used to transfect the cells to explore the effects of ultrasound-microbubble mediated miR-128 on doxorubicin resistance in cancer cells. The CCK8 experiment was used to detect the activity of breast cancer cells; qPCR was used to detect the effect of overexpression of miR-128 on PTEN and the effect on doxorubicin resistance of breast cancer cells. Results miR-128 was under-expressed in doxorubicin-resistant breast cancer cells; overexpression of miR-128 increased the sensitivity of breast cancer cells to doxorubicin,ultrasound-microbubble mediated miR-128 further enhanced breast cancer cells sensitivity to doxorubicin; miR-128 promote resistance to doxorubicin in breast cancer cells by regulating PTEN. Conclusion Overexpression of miR-128 could enhance the sensitivity of breast cancer to doxorubicin. Ultrasound-microbubble mediated miR-128 further enhanced the sensitivity. This study provided a treatment for doxorubicin resistance in breast cancer with new molecular targets and therapeutic approaches.

目的 探讨骨髓间充质干细胞源性微泡(BMSC-MV)修复大鼠早发性卵巢功能不全的自噬机制。方法 大鼠骨髓分离培养骨髓间充质干细胞;超速离心法从骨髓间充质干细胞培养液中分离微泡;腹腔注射顺铂溶液制备早发性卵巢功能不全(POI)模型,制备后3 d尾静脉取血ELISA检测血清雌二醇(E2)及卵泡刺激素(FSH);尾静脉注射BMSC-MV移植治疗POI大鼠模型,移植后28 d尾静脉取血ELISA检测E2、FSH及抗苗勒管激素(AMH),同时取卵巢组织检测自噬相关蛋白LC3及P62。结果 模型对照组及微泡移植组在模型制备后3 d的E2 含量低于正常对照组,FSH 含量高于正常对照组(P<0.001);微泡移植组在移植后28 d的E2、AMH含量高于模型对照组(P<0.001),FSH含量低于模型对照组(P<0.001);微泡移植组的LC3较模型对照组表达升高,而P62表达降低(P<0.001)。结论 BMSC-MV介导自噬修复大鼠早发性卵巢功能不全。

Objective To investigate the autophagy mechanism of bone marrow mesenchymal stem cell-derived microvesicle (BMSC-MV) in repairing premature ovarian dysfunction in rats. Methods The whole bone marrow adherence method was used to isolate,culture and identify BMSCs of SD rats. Microvesicles were isolated from bone marrow mesenchymal stem cell by ultracentrifugation. Premature ovarian insufficiency (POI) model was prepared by intraperitoneal injection of cisplatin solution,and serum estradiol (E2) and follicular stimulating hormone (FSH) were detected by ELISA from tail vein 3 days after preparation. Rat model of POI was treated with BMSC-MV transplantation by tail vein. Blood from tail vein was collected 28 days after transplantation to detect E2,FSH and AMH by ELISA. Meanwhile,ovarian tissues were collected to detect autophagy-related proteins LC3 and P62. Results The E2 content of the model control group and the microvesicle transplantation group was lower than that of the normal control group,and the FSH content was higher than that of the normal control group (P<0.001). The content of E2 and AMH in the microvesicle transplantation group at 28 days after transplantation was higher than that in the model control group (P<0.001),and the content of FSH was lower than that in the model control group (P<0.001). Compared with the model control group,LC3 expression in the microvesicle transplantation group was increased,while P62 expression was decreased (P<0.001). Conclusion BMSC -MV mediate autophagy to repair premature ovarian insufficiency in rats.

目的 探讨低频脉冲超声联合微泡对微血管的渗出作用。方法 20只新西兰大白兔分为4组:空白组、单纯微泡组、单纯超声组、超声微泡组,进行实验观察。用频率为1 MHz,声压2000 MPa的脉冲超声辐照兔肠系膜及肠壁血管,在荧光显微镜下观察辐照前后肠系膜及肠壁上微血管的损伤,并静脉注入伊文思蓝溶液,观察超声辐照后对伊文思蓝溶液的渗出。结果 空白组、单纯微泡组、单纯超声组在超声辐照后肠系膜及肠壁上微血管内血流通畅,注入伊文思蓝溶液后,微血管内呈蓝色染色,血管周围未见渗出;超声微泡组在超声辐照后微血管周围可见渗出,部分形成血肿。结论 低频脉冲超声联合微泡对微小血管管壁产生损伤作用,血管周围可见渗出,部分形成血肿。

目的 探讨微泡增强的超声空化对荷瘤兔乳腺癌的治疗效果。方法 建立兔VX2乳腺癌模型,肿瘤兔随机分成两组,超声微泡组及单纯超声组,各组于治疗前及治疗后分别行超声造影,分析造影前后肿瘤灌注情况。结果 超声微泡组治疗前后造影灰阶值改变明显,造影灰阶值从治疗前的(20.26±2.59)降至(3.71±1.61)(P<0.01);而单纯超声组肿瘤造影灰阶值无明显统计学差异(P>0.05)。结论 微泡增强的超声空化对荷瘤兔乳腺癌有一定的治疗效果。

Objective To investigate the treatment effect of microbubbles-enhanced ultrasound cavitation on VX2 breast tumor in rabbits. Methods The rabbit model of VX2 breast tumor were established. The rabbits were randomly divided into two groups, microbubbles-enhanced ultrasound (US+MBs) group and standard ultrasound (US) group. The VX2 breast tumor perfusion were imaged and assessed using contrast enhanced ultrasonography (CUES) before and after treatment. Results The contrast enhanced grayscale value (GSV) of VX2 breast tumors decreased significantly in the US+MBs group, from 20.26±0.59(before treatment) to 3.71±.761 (after treatment)(P<0.01). While there was no significance of GSV before and after treatment (P>0.05) in the US group. Conclusion Microbubble-enhancement ultrasound cavitation has a certain therapeutic effect on the VX2 breast tumor in rabbits.

目的 探讨微泡增强的超声空化增加睾丸组织的药物浓度的可行性。方法 18只雄性8月龄性成熟新西兰兔随机分为空白对照组(C)、单纯微泡组(MB)、治疗超声组(TUS)、超声联合微泡辐照组(MEUS)4组,每组各9个。MB组给予静注微泡造影剂 0.1 mL/kg ;TUS组给予超声辐照5min;MEUS组给予静注微泡造影剂0.1 mL/kg的同时超声辐照5min;每组在治疗前5min均经耳缘静脉注射2%伊文思蓝(EB)2.5 mL/kg;治疗后1 h取各组睾丸组织制备组织匀浆测量 EB 浓度。结果 MEUS组兔睾丸组织内 EB 浓度高于其他各组(P<0.05),差异有统计学意义。结论 微泡增强的超声空化可以明显提高睾丸组织内EB浓度。

Objective To investigate feasibility of microbubbles enhanced ultrasound (MEUS) on the concentration of Evans blue (EB) in rabbit,stestis. Methods Eighteen sexually mature male New Zealand rabbits were divided into four groups randomly. Pulsed ultrasound irradiation and intravenous microbubbles injection were both applied in the microbubbles enhanced ultrasound group (MEUS), pulsed ultrasound irradiation and intravenous microbubbles injection were individually applied in the therapeutic ultrasound group (TUS) and the simple microbubbles group (MB). Injection of EB was applied in each group five minutes before the treatment.Concentration of EB in testis tissue was measured homogenated. Results The concentration of Evans blue(EB) in rabbit's testis in MEUS group was statistically higher than the other groups (P<0.05). Conclusion Microbubbles enhanced ultrasound (MEUS) can increase the concentration of Evans blue (EB) in rabbit's testis.

目的 初步探讨微泡增强的脉冲式超声治疗脾创伤出血的作用机制。方法 14只健康家犬随机分为3组,超声微泡组(MEUS组)6只、单纯超声组(TUS组)4只、单纯微泡组(MB组)4只。开腹切割脾建立脾破裂出血模型,MEUS组用脉冲式超声治疗仪辐照伤口,同时静脉匀速推注微泡;TUS组超声治疗时静脉推注生理盐水;MB组超声治疗仪假照的同时静脉推注微泡。治疗完毕,进行超声造影评价,并送病理组织学检查。结果 MEUS组造影示靶区造影增强缺损或者低灌注,但较粗大血管仍为增强显影。病理组织学见脾窦、微小血管扩张充血、血管周围组织水肿,血小板聚集,微小血管血栓形成。结论 微小血管血栓形成、微血管淤血扩张、周围组织水肿压迫是超声联合微泡治疗脾创伤出血的可能机理。

Objective To investigate the mechanism of haemostatic effect induced by microbubble(MB)enhanced therapeutic ultrasound(TUS)on splenic trauma. Methods 14 healthy dogs were divided into 3 groups.Six animals were treated by microbubble-enhanced therapeutic ultrasound(MEUS),the other eight animals were treated with TUS only group(n=4)and the MB only(n=4)served as the controls.The spleens of all animals were surgically exposed and a 20 mm long,5 mm deep incision was created on the spleens using scalpel.Contrast enhanced ultrasound(CEUS)was performed to assess the blocking effects of splenic circulation.The targeted spleens were harvested for pathological examination. Results A non-enhanced or perfusion defect region was formed within the treated area.The histological results showed splenic sinus hyperemia,microvascular hyperemia,perivascular tissue edema,platelet aggregation and intravascular thrombosis. Conclusion The mechanism of haemostatic effect on splenic trauma by microbubble enhanced ultrasound maybe intravascular thrombosis,microvascular hyperemia and perivascular tissue edema oppression simultaneously.