本文關(guān)鍵詞：鈉鉀合金消融治療小鼠胰腺癌　出處：《河北醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 微創(chuàng)治療 腫瘤消融 鈉鉀合金 早期腫瘤 晚期腫瘤

【摘要】：目的:癌癥是威脅人類健康的一個(gè)重大問(wèn)題,全世界每年大約有1400萬(wàn)新發(fā)癌癥患者,并有將近800萬(wàn)人死于癌癥。找到一個(gè)與癌癥分期相關(guān)的腫瘤治療方法至關(guān)重要。局部消融技術(shù)作為一種微創(chuàng)治療方法被廣泛應(yīng)用于惡性腫瘤治療。鈉鉀合金消融的方法打破傳統(tǒng)消融的理念,通過(guò)鈉鉀合金與組織中的水分發(fā)生化學(xué)反應(yīng),釋放能量。反應(yīng)物鈉和鉀作為人體的基本元素,可以完全被吸收。通過(guò)注射器將很少量液態(tài)的鈉鉀合金注射到目標(biāo)組織,局部產(chǎn)生高溫,反應(yīng)同時(shí)生成氫氧根和氫氣。氫氧根產(chǎn)生類似于電化學(xué)反應(yīng)中正負(fù)極的作用,形成堿性環(huán)境,對(duì)腫瘤組織起到殺傷作用。另一方面,反應(yīng)產(chǎn)生的氣體在腫瘤組織內(nèi)部發(fā)生氣穴效應(yīng),依靠氣體沖擊造成細(xì)胞的機(jī)械性壞死破裂。目前并沒(méi)有關(guān)于鈉鉀合金對(duì)早期及晚期胰腺癌小鼠療效的報(bào)道,此次采用經(jīng)皮穿刺鈉鉀合金消融技術(shù),術(shù)后精確記錄小鼠腫瘤體積和重量的方法,評(píng)估鈉鉀合金消融對(duì)小鼠早期腫瘤和晚期腫瘤的治療效果,為腫瘤臨床治療提供一個(gè)新方向。方法:將Panc02胰腺癌細(xì)胞制成濃度為1×107/ml的懸浮液,注射到21只雌性C57BL/6小鼠中,每只注射0.2ml,約2×106個(gè)腫瘤細(xì)胞,建立腫瘤小鼠模型。每?jī)商鞙y(cè)量一次腫瘤體積。小鼠隨機(jī)分為早期腫瘤組(ET組,腫瘤平均體積約為150mm3),晚期腫瘤組(DT組,腫瘤平均體積約為550mm3)和對(duì)照組(CO組,腫瘤平均體積約為550mm3)共3組。1早期腫瘤組7只小鼠在接種腫瘤細(xì)胞后第18天,向小鼠腫瘤中心注射15uL鈉鉀合金進(jìn)行消融治療,注射過(guò)程用熱電偶、紅外熱像儀監(jiān)測(cè)溫度變化。腫瘤消融術(shù)后,早期腫瘤組隨機(jī)選取兩只小鼠處死,切取消融區(qū)的腫瘤組織制成病理切片。2晚期腫瘤組7只小鼠在接種腫瘤細(xì)胞后第25天,向小鼠腫瘤中心注射15uL鈉鉀合金,同時(shí)用熱電偶、紅外熱像儀監(jiān)測(cè)。腫瘤消融術(shù)后,晚期腫瘤組隨機(jī)選取兩只小鼠處死,切取消融區(qū)的腫瘤組織制成病理切片。3對(duì)照組7只小鼠不進(jìn)行鈉鉀合金消融,在接種腫瘤細(xì)胞后第25天,向小鼠腫瘤中心注射15ul生理鹽水,同時(shí)用熱電偶、紅外熱像儀監(jiān)測(cè)。注射完成后,隨機(jī)選取兩只小鼠處死,切取腫瘤組織制成病理切片。繼續(xù)觀察17天,剩余小鼠全部處死。切取腫瘤組織并稱重,計(jì)算抑瘤率。結(jié)果:1溫度變化溫度時(shí)間曲線揭示了消融區(qū)中心溫度變化,小鼠機(jī)體正常溫度為33℃(t0),當(dāng)堿金屬合金注入到腫瘤中心(t=0),溫度在兩秒內(nèi)迅速由33℃升高至85℃。最高溫度維持不到1秒鐘,逐漸減低,直到恢復(fù)至起始溫度。反應(yīng)釋放大量熱能,溫度可以保持在42℃以上長(zhǎng)達(dá)50秒。紅外熱像儀放置在小鼠上方10cm處,記錄小鼠表面皮膚溫度。紅色區(qū)域?yàn)樯郎貐^(qū)域,注射鈉鉀合金時(shí),升溫范圍最大,形狀類似腫瘤,越靠近注射點(diǎn)溫度越高。此時(shí)小鼠其他部位體溫基本維持不變。隨著消融結(jié)束,深紅顏色區(qū)域即溫度為40℃的范圍,向注射中心逐漸縮小。腫瘤組織溫度升高可以維持約50秒。2病理組織切片早期腫瘤組可以看到明顯的凝固性壞死,細(xì)胞核碎裂溶解,細(xì)胞結(jié)構(gòu)完全消失,呈均質(zhì)紅染。晚期腫瘤組細(xì)胞發(fā)生不完全壞死,界限分明。部分為完整的腫瘤細(xì)胞,細(xì)胞核大染色深,細(xì)胞核異形性顯著。部分為不完全壞死的腫瘤細(xì)胞。細(xì)胞核碎裂,細(xì)胞腫脹壞死。對(duì)照組的腫瘤細(xì)胞結(jié)構(gòu)完整,異形性明顯,細(xì)胞核數(shù)量多顏色深,染色質(zhì)豐富。3腫瘤體積測(cè)量腫瘤細(xì)胞在小鼠腹膜內(nèi)接種后生長(zhǎng)良好,腫瘤體積迅速增大。早期腫瘤組在接受堿金屬消融時(shí),腫瘤體積約為180mm3,術(shù)后腫瘤體積迅速下降,逐漸形成硬痂,腫瘤幾乎完全消失,到消融術(shù)后第24天,測(cè)量硬痂處腫瘤體積約為33mm3。晚期組腫瘤在消融術(shù)后迅速縮小,至260mm3。由于晚期腫瘤體積大、形狀不規(guī)則,消融不完全,腫瘤體積在消融術(shù)后10天開(kāi)始增長(zhǎng),觀察結(jié)束時(shí),體積約為560mm3。對(duì)照組小鼠體積一直不斷增大。在接種后0-20天,對(duì)照組腫瘤幾乎呈對(duì)數(shù)生長(zhǎng)。20天后腫瘤生長(zhǎng)逐漸減緩,實(shí)驗(yàn)結(jié)束時(shí)未消融組腫瘤平均體積為3300mm3。4腫瘤抑瘤率在觀察結(jié)束時(shí),小鼠被全部處死,取出腫瘤測(cè)量重量,早期腫瘤組平均瘤重0.21g,消融治療的抑瘤率為88.5%(P0.05),有統(tǒng)計(jì)學(xué)意義。晚期腫瘤組平均瘤重0.58g,消融治療的抑瘤率為67.6%(P0.05),有統(tǒng)計(jì)學(xué)意義。結(jié)論:1微量的鈉鉀合金可以釋放高能熱量,集中作用于腫瘤區(qū)域,使腫瘤細(xì)胞發(fā)生明顯的凝固性壞死,迅速消融腫瘤。2鈉鉀合金對(duì)早期腫瘤可以達(dá)到完全消融;對(duì)晚期腫瘤可以減輕小鼠腫瘤負(fù)荷,在一定時(shí)間內(nèi)抑制腫瘤生長(zhǎng)。
[Abstract]:Objective: cancer is a major threat to human health, there are about 1400 millionnew cancer patients worldwide each year, and nearly 8 million people died of cancer. To find a method for cancer therapy and cancer staging is crucial. Local ablation is a minimally invasive treatment technology is widely used in the treatment of malignant tumors. Methods the sodium potassium alloy ablation to break the traditional concept of ablation, chemical reaction, the sodium potassium alloy and the water release energy. Reaction of sodium and potassium as the basic element of the human body, can be completely absorbed by the injector. Will is a small amount of liquid sodium potassium alloy injection to the target tissue, local high temperature reaction, at the same time generation of hydroxyl and hydroxyl hydrogen. Similar to those produced positive and negative effect of electrochemical reaction, the formation of alkaline environment to the killing effect on tumor tissue. On the other hand, reaction yield The gas generating cavitation effect in tumor tissue, depending on the gas shock caused by mechanical necrotic cell rupture. There is no report about the effect of sodium potassium alloy in early and advanced pancreatic cancer in mice, the sodium potassium alloy using percutaneous ablation techniques, postoperative accurate recording method of mouse tumor volume and weight. On early mouse tumors and advanced tumor ablation treatment effect evaluation of sodium potassium alloy, providing a new direction for the clinical treatment of tumors. Methods: Panc02 pancreatic cancer cells into the concentration of 1 * 107/ml suspension was injected into the 21 female C57BL/6 mice, each injection of 0.2ml, about 2 x 106 tumor cells and establish tumor models in mice were measured every two days. Once the volume of the tumor. The mice were randomly divided into early tumor group (ET group, the average tumor volume is about 150mm3), advanced tumor group (DT group, the average tumor volume is about 550mm3) and The control group (CO group, the average tumor volume of about 550mm3) a total of 3 group.1 group of 7 mice in the early stage of tumor inoculation of tumor cells after eighteenth days of treatment to the tumor ablation center of mice injected with 15uL sodium potassium alloy, thermocouple for injection process, to monitor the temperature change of infrared thermography. After tumor ablation, early tumor group randomly selected two mice were sacrificed, cut the ablation area of tumor tissue made pathologic slices of.2 cancer group of 7 mice inoculated with tumor cells after twenty-fifth days, mice were injected with 15uL alloy to the tumor center of sodium potassium, and thermocouple, thermal infrared imager monitoring. After tumor ablation, advanced cancer were randomly selected in two mice were sacrificed, cut the ablation zone of the tumor tissue sections were prepared for.3 sodium potassium alloy ablation control group of 7 mice in twenty-fifth days after inoculation of tumor cells, to the center of tumor mice were injected with 15ul saline at the same time, with power Occasionally, infrared monitoring. After injection, two randomly selected mice were sacrificed, cut the tumor tissue sections were prepared. To observe 17 days, the remaining mice were harvested and weighed. The tumor tissue, the inhibition rate was calculated. Results: 1 temperature time curve reveals the ablation zone center temperature changes, normal the temperature is 33 DEG C mice (T0), when the alkali metal alloy is injected into the center of tumor (t=0), the temperature rapidly within two seconds from 33 degrees to 85 degrees. The highest temperature rise remain less than 1 seconds, decreased gradually, until the return to the initial temperature. The reaction release large amounts of heat, the temperature can be maintained at 42 DEG C for more than 50 seconds. The infrared thermal imager is placed in the mice at 10cm above the surface skin temperature, were recorded. The red area for heating area, injection of sodium potassium alloy, the maximum temperature range, similar in shape to tumor, the more close to the injection point. The higher the temperature at this time of mice The temperature of other parts unchanged. With the end of ablation, deep red color region that is temperature range of 40 DEG C, gradually reduced to the injection center. Tumor tissue temperature can last about 50 seconds.2 pathological sections of early tumor group can see obvious coagulation necrosis, cell nuclear fragmentation dissolved, cell structure disappeared completely, is homogeneous red staining. Late tumor group occurred incomplete cell necrosis, clear boundaries. As part of complete tumor cells, nuclear staining deep, nuclear atypia significantly. Part of incomplete necrosis of tumor cells. Nuclear fragmentation, cell swelling and necrosis of tumor cells. The control group structure integrity, shaped significantly more than the number of nuclei the color is deep, rich chromatin were inoculated with.3 tumor volume measurement of tumor cells in mice after intraperitoneal growth, tumor volume increases rapidly. The early tumor group in an alkali metal ablation When the tumor volume is about 180mm3, postoperative tumor volume decreased rapidly, gradually formed a crust, the tumor had almost completely disappeared, twenty-fourth days after ablation, measuring hard callus tumor volume is about 33mm3. in the late group tumor shrinks quickly after ablation, due to 260mm3. advanced tumor volume, irregular shape, no ablation totally, the tumor volume growth in the first 10 days after ablation, the end of the observation volume is about 560mm3., the mice of control group has been increasing in volume. 0-20 days after inoculation, the tumor control group was almost logarithmic.20 days after tumor growth gradually slowed down, at the end of the experiment without ablation group the average tumor volume for tumor inhibition rate in 3300mm3.4 at the end of experiment, the mice were killed, remove the measurement of tumor weight, tumor early group average tumor weight 0.21g, ablation rate of tumor was 88.5% (P0.05), was statistically significant. The average tumor weight of 0. advanced cancer group 58G, ablation rate of tumor was 67.6% (P0.05), there was statistical significance. Conclusion: 1 trace amounts of sodium potassium alloy can release heat energy, concentration in the tumor region, the coagulative necrosis of tumor cells significantly, rapid tumor ablation.2 sodium potassium alloy for early tumor can achieve complete ablation of advanced; the tumor can reduce the tumor load, inhibit tumor growth in a certain period of time.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.9

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