姜黄素对N-甲基亚硝基脲诱发膀胱癌大鼠化学干预作用及机制分析

发布时间：2018-02-22 22:07

本文关键词： 姜黄素 N-甲基亚硝基脲膀胱癌化学干预作用机制大鼠　出处：《中国实验动物学报》2017年05期 　论文类型：期刊论文

【摘要】：目的分析姜黄素对N-甲基亚硝基脲(MNU)诱导的膀胱癌大鼠模型的化学干预作用及作用机制。方法将100只SD大鼠随机分为四组,对照组(10只)、模型组(10只)、干预组(40只)和治疗组(40只),对照组等时等量的膀胱灌注生理盐水,其他三组均对大鼠进行膀胱灌注MNU,诱发SD大鼠形成膀胱癌模型(将浓度为1 mg/m L的MNU溶液灌注入膀胱内,MNU灌注时间为第2、4、6和8周,每次2 mg,每2周1次,共4次),模型组在诱发大鼠膀胱癌时膀胱灌注蒸馏水,干预组在膀胱灌注MNU时灌注姜黄素溶液(400μmol/L),即第1、3、5、7和9周膀胱灌注,第10周安乐死大鼠;治疗组在诱发大鼠膀胱癌模型后膀胱灌注姜黄素溶液(400μmol/L),即在第10、12、14、16、18周时间内持续膀胱灌注,在第19周时处死大鼠,获得的膀胱组织依次通过苏木精-伊红(HE)染色,观察病理变化;TUNEL末端标记法测定肿瘤组织中细胞凋亡情况;Western blot检测凋亡相关蛋白表达。结果模型组在第10周时膀胱癌的发生率为90%(9/10),干预组在第10周时大鼠膀胱癌的发生率为12.5%(5/40),治疗组第10周时膀胱癌的发生率为92.5%(37/40),比较干预组与模型组大鼠膀胱癌的发生率差异有显著性(P0.05),说明姜黄素对MUN诱发膀胱癌大鼠有明显的化学干预作用;在治疗组膀胱癌形成后给予姜黄素治疗,第19周膀胱癌发生率为78.4%(30/37),与治疗前的第10周比较说明姜黄素对膀胱癌有治疗作用,可以延缓膀胱癌的恶化。TUNEL实验证实姜黄素显著促进膀胱癌细胞的凋亡,抑制膀胱癌细胞的增殖。Western blot结果发现,姜黄素抑制NF-κB的激活,有效下调NF-κB调节的基因产物的表达。结论姜黄素对MNU诱导的膀胱癌大鼠模型有明显的的化学干预作用,且作用机制可能是通过抑制NF-κB的激活并且有效下调NF-κB调节的基因产物,来调节膀胱癌中相关蛋白的表达机制,即抑制增殖,诱导凋亡,进一步发挥抗癌的化学干预作用以及预防膀胱癌的复发。
[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.
【作者单位】：青岛大学;潍坊医学院;
【分类号】：R737.14

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