脂质体槲皮素对微波消融兔肝组织疗效影响的研究

发布时间：2018-06-19 08:40

本文选题：脂质体槲皮素 + 微波消融　；参考：《郑州大学》2017年硕士论文

【摘要】：目的:通过观察静脉注射(IV)脂质体槲皮素(LQ)联合微波消融(MWA)、MWA及IV LQ对正常兔肝脏的消融效果及其相关分子改变,研究IV LQ对MWA消融效果的影响及其相关分子机制,为后期消融肿瘤组织奠定理论基础。材料和方法:48只日本大耳白兔随机平分为3组,每组16只:IV LQ组,MWA组和IV LQ联合MWA(LQ+MWA)组,其中IV LQ组和LQ+MWA组均于消融术前24小时经兔耳缘静脉注射脂质体槲皮素(0.5mg/kg)。分别于消融术后12小时,24小时,3天和7天收集血清标本和肝脏组织样本。比较术后第7天正常肝实质的凝固性坏死体积(CV),同时比较并总结各组间不同时间点较为典型的组织病理学特征。通过检测并比较消融周边区热休克蛋白70(HSP70)、缺氧诱导因子-1α(HIF-1α)及Ki 67表达水平及消融周边肝组织中凋亡细胞,同时检测血清中的肿瘤坏死因子-α(TNF-α)表达水平,进一步研究IV LQ对MWA消融兔肝组织的影响及其相关分子机制。结果:消融术后第7天,LQ+MWA组肝脏组织凝固性坏死体积(CV)明显高于MWA组。MWA和LQ+MWA组中,HSP70和HIF-1α表达水平于消融术后12和24小表达增加,第3天达到峰值,术后第7天下降;同时,消融周边区肝组织中表达的HSP70 mRNA和HIF-1αmRNA于术后12小时和24小时表达增加,第3天达到峰值,术后第7天下降。与MWA相比,LQ+MWA组在所有时间点中HSP70、HIF-1α和Ki67表达明显降低,而血清中TNF-α表达较之增加。LQ+MWA组于术后12小时,24小时和3天肝细胞凋亡率均高于MWA组,而两组间于术后7天肝细胞凋亡率却无明显差别。结论:1.IV LQ是通过抑制消融周边区肝组织内HSP70和HIF-1α的表达,改善血清TNF-α的表达,进而增加肝细胞凋亡和MWA诱导的兔肝实质破坏,增加MWA消融效果。2.IV LQ在诱导肝细胞凋亡同时也抑制Ki67的表达,从而降低残余肝细胞增殖,为后期消融兔肝VX2肿瘤模型及降低局部肿瘤复发率奠定理论基础。
[Abstract]:Objective: to investigate the effect of intravenous injection of liposome quercetin (LQ) and microwave ablation (MWA) and IVLQ (IV LQ) on normal rabbit liver and its molecular changes, and to investigate the effects of IVLQ on the ablation of MWA and its molecular mechanisms. To lay a theoretical foundation for the later ablation of tumor tissue. Materials and methods Forty-eight Japanese white rabbits were randomly divided into 3 groups, 16 in each group: MWA group and IVLQ combined with MWALQ MWALWA group. The IVLQ and LQ MWA groups were injected with quercetin 0.5 mg / kg through the ear of rabbits 24 hours before ablation. Serum samples and liver tissue samples were collected at 12 hours and 24 hours after ablation for 3 and 7 days, respectively. The coagulative necrotic volume of normal hepatic parenchyma was compared on the 7th day after operation, and the histopathological features at different time points were compared and summarized. The expressions of heat shock protein 70 (HSP70), hypoxia inducible factor-1 伪 (HIF-1 伪), Ki67 and apoptotic cells in the surrounding liver tissue were detected and compared, and the expression of tumor necrosis factor- 伪 (TNF- 伪) in serum was also detected. To further study the effect of IVLQ on the liver tissue of MWA ablation rabbits and its molecular mechanism. Results: the expression levels of HSP70 and HIF-1 伪 in LQ MWA group were significantly higher than those in MWA group and LQ MWA group on the 7th day after ablation, which were significantly higher than those in MWA group and LQ MWA group. The expression of HSP70 mRNA and HIF-1 伪 mRNA increased at 12 and 24 hours after ablation, reached the peak on the 3rd day, and decreased on the 7th day after ablation. Compared with MWA, the expression of HSP70 HIF-1 伪 and Ki67 in LQ MWA group was significantly lower than that in MWA group at all time points, while the expression of TNF- 伪 in serum was higher in LQ MWA group than in MWA group at 24 hours and 3 days after operation, and the apoptotic rate of hepatocytes in LQ MWA group was higher than that in MWA group at 12 hours and 3 days after operation. However, there was no significant difference between the two groups in the rate of hepatocyte apoptosis 7 days after operation. Conclusion: 1. By inhibiting the expression of HSP70 and HIF-1 伪 in the liver tissue around the ablation area, the expression of TNF- 伪 in serum was improved, and the apoptosis of hepatocyte and the damage of hepatic parenchyma induced by MWA were increased by the inhibition of HSP70 and HIF-1 伪 expression. Increase the effect of MWA ablation. 2. IVLQ can induce hepatocyte apoptosis and inhibit Ki67 expression, which can reduce the proliferation of residual hepatocytes and lay a theoretical foundation for the later ablation of rabbit liver VX2 tumor model and the reduction of local tumor recurrence rate.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.7

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