本文關(guān)鍵詞： 姜黃素 N-甲基亞硝基脲 膀胱癌 化學(xué)干預(yù) 作用機(jī)制 大鼠　出處：《中國(guó)實(shí)驗(yàn)動(dòng)物學(xué)報(bào)》2017年05期 　論文類型：期刊論文

【摘要】：目的分析姜黃素對(duì)N-甲基亞硝基脲(MNU)誘導(dǎo)的膀胱癌大鼠模型的化學(xué)干預(yù)作用及作用機(jī)制。方法將100只SD大鼠隨機(jī)分為四組,對(duì)照組(10只)、模型組(10只)、干預(yù)組(40只)和治療組(40只),對(duì)照組等時(shí)等量的膀胱灌注生理鹽水,其他三組均對(duì)大鼠進(jìn)行膀胱灌注MNU,誘發(fā)SD大鼠形成膀胱癌模型(將濃度為1 mg/m L的MNU溶液灌注入膀胱內(nèi),MNU灌注時(shí)間為第2、4、6和8周,每次2 mg,每2周1次,共4次),模型組在誘發(fā)大鼠膀胱癌時(shí)膀胱灌注蒸餾水,干預(yù)組在膀胱灌注MNU時(shí)灌注姜黃素溶液(400μmol/L),即第1、3、5、7和9周膀胱灌注,第10周安樂(lè)死大鼠;治療組在誘發(fā)大鼠膀胱癌模型后膀胱灌注姜黃素溶液(400μmol/L),即在第10、12、14、16、18周時(shí)間內(nèi)持續(xù)膀胱灌注,在第19周時(shí)處死大鼠,獲得的膀胱組織依次通過(guò)蘇木精-伊紅(HE)染色,觀察病理變化;TUNEL末端標(biāo)記法測(cè)定腫瘤組織中細(xì)胞凋亡情況;Western blot檢測(cè)凋亡相關(guān)蛋白表達(dá)。結(jié)果模型組在第10周時(shí)膀胱癌的發(fā)生率為90%(9/10),干預(yù)組在第10周時(shí)大鼠膀胱癌的發(fā)生率為12.5%(5/40),治療組第10周時(shí)膀胱癌的發(fā)生率為92.5%(37/40),比較干預(yù)組與模型組大鼠膀胱癌的發(fā)生率差異有顯著性(P0.05),說(shuō)明姜黃素對(duì)MUN誘發(fā)膀胱癌大鼠有明顯的化學(xué)干預(yù)作用;在治療組膀胱癌形成后給予姜黃素治療,第19周膀胱癌發(fā)生率為78.4%(30/37),與治療前的第10周比較說(shuō)明姜黃素對(duì)膀胱癌有治療作用,可以延緩膀胱癌的惡化。TUNEL實(shí)驗(yàn)證實(shí)姜黃素顯著促進(jìn)膀胱癌細(xì)胞的凋亡,抑制膀胱癌細(xì)胞的增殖。Western blot結(jié)果發(fā)現(xiàn),姜黃素抑制NF-κB的激活,有效下調(diào)NF-κB調(diào)節(jié)的基因產(chǎn)物的表達(dá)。結(jié)論姜黃素對(duì)MNU誘導(dǎo)的膀胱癌大鼠模型有明顯的的化學(xué)干預(yù)作用,且作用機(jī)制可能是通過(guò)抑制NF-κB的激活并且有效下調(diào)NF-κB調(diào)節(jié)的基因產(chǎn)物,來(lái)調(diào)節(jié)膀胱癌中相關(guān)蛋白的表達(dá)機(jī)制,即抑制增殖,誘導(dǎo)凋亡,進(jìn)一步發(fā)揮抗癌的化學(xué)干預(yù)作用以及預(yù)防膀胱癌的復(fù)發(fā)。
[Abstract]:Objective to analyze the chemical effect and mechanism of curcumin on bladder cancer induced by N-methyl-nitroso (MNU) in rats. Methods 100 SD rats were randomly divided into four groups. Control group (n = 10), model group (n = 10), intervention group (n = 40) and treatment group (n = 40). The other three groups were given intravesical instillation of MNU to induce bladder cancer model in SD rats. The intravesical instillation time of 1 mg/m L MNU solution into the bladder was 2mg2 mg once every 2 weeks. The model group was injected with distilled water during the induction of bladder cancer, and the intervention group was infused with curcumin solution (400 渭 mol / L) at the time of intravesical instillation of MNU, I. E. intravesical instillation of curcumin solution at the 7th and 9th weeks, and euthanasia at the 10th week. In the treatment group, the bladder was infused with curcumin solution of 400 渭 mol / L after the bladder cancer model was induced, that is, the bladder perfusion lasted for 18 weeks at 1012 ~ 14U / L, and the rats were killed at the 19th week. The bladder tissue was stained by hematoxylin-eosin (HEH) in turn, and the bladder tissue of the treated group was stained by hematoxylin-eosin (HEH). The expression of apoptosis-related protein in tumor tissue was detected by blot. Results the incidence of bladder cancer in the model group was 90 / 10 at the 10th week, and that in the intervention group was 9 / 10 at the 10th week. The incidence of bladder cancer in the treatment group was 92.5 / 37 / 40 at the 10th week. There was significant difference in the incidence of bladder cancer between the intervention group and the model group (P 0.05), which indicated that curcumin had a significant chemical intervention effect on MUN induced bladder cancer in rats. In the treatment group, curcumin was given after the formation of bladder cancer, and the incidence of bladder cancer was 78.4% at the 19th week. Compared with the 10th week before treatment, curcumin had a therapeutic effect on bladder cancer. The results showed that curcumin significantly promoted the apoptosis of bladder cancer cells and inhibited the proliferation of bladder cancer cells. Western blot showed that curcumin inhibited the activation of NF- 魏 B, and curcumin inhibited the activation of NF- 魏 B in bladder cancer cells. Conclusion curcumin can inhibit the expression of NF- 魏 B regulated gene product in MNU induced bladder cancer rat model, and the mechanism may be that curcumin can inhibit the activation of NF- 魏 B and down-regulate NF- 魏 B regulatory gene product. To regulate the expression of related proteins in bladder cancer, that is, to inhibit proliferation, induce apoptosis, further play the role of anti-cancer chemical intervention and prevent the recurrence of bladder cancer.
【作者單位】： 青島大學(xué);濰坊醫(yī)學(xué)院;
【分類號(hào)】：R737.14

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