【摘要】：目的：藤黃對錯配修復(fù)基因hMLH1缺失的結(jié)直腸腫瘤毒效相關(guān)性研究。方法：利用能表達(dá)綠色熒光蛋白人結(jié)直腸癌HCT116細(xì)胞,在無菌環(huán)境下通過外科手術(shù)建立裸鼠結(jié)腸癌模型。分別將HCTll6細(xì)胞原位移植成功的荷瘤鼠隨機(jī)分為6組,每組8只。根據(jù)急毒試驗(yàn)中LD50的結(jié)果,將藤黃配置成3種高、中、低濃度作為實(shí)驗(yàn)組,生理鹽水為陰性對照組,5-FU、伊立替康為陽性對照組。藤黃組分別給予高中低三種劑量的藤黃灌胃,1次/日；陽性對照組組分別予5-氟尿嘧啶、伊立替康腹腔灌注,隔日給藥1次。每日觀察記錄動物死亡情況、營養(yǎng)及活動狀態(tài),不良反應(yīng),在固定時間點(diǎn)分別應(yīng)用動物活體熒光影像系統(tǒng)測量腫瘤大小,并稱體重。治療25天后,在熒光系統(tǒng)下觀察腫瘤血管密度情況,腫瘤大小及轉(zhuǎn)移情況。結(jié)果：藥物干預(yù)后,實(shí)驗(yàn)終點(diǎn)0.2g/kg藤黃組腫瘤的平均質(zhì)量及平均體積均小于對照組(0.52±0.24g vs 1.21±0.63g; 481.0±226.5mm3 vs 956.5±780.1mm3),差異均有統(tǒng)計學(xué)意義(P0.05)。鹽酸伊立替康組腫瘤的平均質(zhì)量及平均體積均小于對照組(0.28±0.13g vs 1.21±0.63g; 258.0±126.2mm3 vs 956.5±780.1mm3),差異均有統(tǒng)計學(xué)意義(P0.05)。0.1g/kg藤黃組、0.05g/kg藤黃組與5-FU組對照組比較,各組腫瘤的平均質(zhì)量與體積,無論是各觀察點(diǎn)還是實(shí)驗(yàn)終點(diǎn)統(tǒng)計結(jié)果均無統(tǒng)計學(xué)意義(P0.05)。實(shí)驗(yàn)結(jié)束后觀察,在熒光系統(tǒng)下各組荷瘤小鼠體內(nèi)均有不同程度的胰腺及淋巴結(jié)轉(zhuǎn)移,實(shí)驗(yàn)過程中(除預(yù)實(shí)驗(yàn))各組實(shí)驗(yàn)動物均未出現(xiàn)藥物相關(guān)的不良反應(yīng),各實(shí)驗(yàn)組的荷瘤裸鼠的個體質(zhì)量尚未出現(xiàn)明顯大的波動。結(jié)論：藤黃在達(dá)到一定干預(yù)劑量(如0.2g/kg)后能有效控制其對小鼠的毒性,基本無毒效反應(yīng)；能抑制人結(jié)腸癌HCT116細(xì)胞裸鼠原位移植瘤的生長,其效果與伊立替康相似,可能具有潛在的臨床抗結(jié)直腸癌作用。
[Abstract]:Objective: to study the relationship between the toxicity of Fujiangyangyangyangyangyangyangyue and hMLH1 deletion of mismatch repair gene in colorectal cancer. Methods: human colorectal cancer HCT116 cells expressing green fluorescent protein were used to establish nude mouse colon cancer model by surgical operation in aseptic environment. Tumor bearing mice successfully transplanted with HCTll6 cells were randomly divided into 6 groups with 8 mice in each group. According to the results of LD50 in acute toxicity test, three kinds of yolk were divided into three groups: high, medium and low concentration as experimental group, normal saline as negative control group, and Iritekang as positive control group. The rats in the Fujinhuang group were given three doses of lianghuang once a day, and the positive control group were given 5-fluorouracil and irinotecan intraperitoneally, once every other day. Daily observation and recording of animal death, nutritional and activity status, adverse reactions, the use of animal in vivo fluorescence imaging system to measure tumor size at a fixed time point, and said weight. After 25 days of treatment, tumor vascular density, tumor size and metastasis were observed under fluorescence system. Results: after drug intervention, the mean mass and volume of tumor in the 0.2g/kg yolk group were significantly lower than those in the control group (0.52 鹵0.24g vs 1.21 鹵0.63g; 481.0 鹵226.5mm3 vs 956.5 鹵780.1mm3) (P0.05). The mean mass and volume of the tumor in the Ilitecam hydrochloride group were lower than those in the control group (0.28 鹵0.13g vs 1.21 鹵0.63g; 258.0 鹵126.2mm3 vs 956.5 鹵780.1mm3). The difference was statistically significant (P0.05). No statistical significance was found in the statistical results of the observation points or the end points of the experiment (P0.05). At the end of the experiment, pancreatic and lymph node metastases were observed in various groups of tumor-bearing mice under fluorescence system, and no drug-related adverse reactions were observed in each group (except for pre-experiment). The individual weight of tumor-bearing nude mice in each experimental group has not been significantly fluctuated. Conclusion: Fujinhuang can effectively control the toxicity of 0.2g/kg to mice and inhibit the growth of orthotopic transplantation of human colon cancer HCT116 cells in nude mice after reaching a certain intervention dose (such as 0.2g/kg), and its effect is similar to that of irinotecan. It may have a potential clinical anti-colorectal cancer effect.
【學(xué)位授予單位】：南京中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R285

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