【作者】 杨国兴；

【导师】 凌昌全； 苏永华；

【作者基本信息】 第二军医大学 ， 中西医结合临床， 2008， 硕士

【摘要】 研究背景:肝细胞癌(Heptocellular carcinoma,HCC,简称肝癌)是我国常见的恶性肿瘤之一,严重威胁人们身体健康,但迄今为止除各种手术方法外,几乎没有有效的治疗药物。糖皮质激素(Glucocorticoid,GC)与肿瘤有着密切的关系,既往有研究报道糖皮质激素能够抑制肝癌细胞的增殖,诱导其凋亡,抑制人卵巢癌增殖并诱导其分化,可能参与抑制人乳腺癌细胞系细胞增殖的过程,抑制肿瘤细胞血管内皮生长因子。糖皮质激素受体(GR)在肿瘤细胞的信号传导、肿瘤相关基因表达和细胞凋亡等过程中发挥重要作用,故其与肿瘤的关系日益受到重视。Ho等观察到多数原发性肝癌的胞质中可发现GR,它是原发性肝癌切除术后的独立预后因素,GR阳性者较GR阴性者生存率低。糖皮质激素受体(GR)在肝肿瘤细胞中含量的研究结果不一,多数作者发现肝硬化病人GR含量下降,而肝细胞癌(hepaticcellular cancer,HCC)患者肝细胞的GR含量增加,糖皮质激素及其受体与肝癌治疗及预后之间的关系急需深入研究。目的:研究原发性肝癌患者糖皮质激素和其糖皮质激素受体的变化及其受影响的机制。方法:1、原发性肝癌组79人和健康人组66人,清晨六点抽静脉血,分离血清,放射免疫法检测糖皮质激素水平。2、分为原发性肝癌组和健康人组,每组各22人,清晨六点抽取静脉血,用流式细胞术检测血内糖皮质激素受体含量,并观察原发性肝癌患者13人在我科中药综合治疗后糖皮质激素受体含量的变化。结果:1、原发性肝癌患者糖皮质激素较健康人降低(P＜0.05),原发性肝癌患者糖皮质激素与其钾、乙型肝炎和肌酐相关,与乙型肝炎呈最大负相关,相关系数为—44.484。健康人糖皮质激素与其肌酐、性别、谷丙转氨酶相关,女性糖皮质激素要低于男性,相关系数为—62.747。原发性肝癌患者经中药治疗后糖皮质激素有所升高(P＜0.01)。2、原发性肝癌患者糖皮质激素受体较健康人降低(P＜0.01),原发性肝癌患者糖皮质激素受体结合力较正常人升高(P＜0.01),原发性肝癌患者治疗后糖皮质激素受体升高(P＜0.01),原发性肝癌患者治疗前后糖皮质激素受体结合力差值无统计学意义(P＞0.5)。结论:1、原发性肝癌患者糖皮质激素水平降低,乙型肝炎可能是患者糖皮质激素降低的重要因素。2、原发性肝癌患者糖皮质激素受体较健康人降低,分析原因可能与以下因素有关:①肝硬化,②肝癌本身导致肝功损害,③原发性肝癌患者GR结合力升高,可能为GR减少造成GR结合力反应性升高所致。3、经过中医综合治疗后,原发性肝癌患者糖皮质激素水平及其受体有明显改变,并且与临床指标相关,提示对糖皮质激素及其受体影响有可能是中药疗效的一个重要作用靶点。但明确的治疗作用有待于后续对患者相关指标的追踪检测以及生存期及生活质量的随访来证实。展望:本研究初步检测了原发性肝癌患者糖皮质激素水平及其受体和受体结合力水平,并与相关病理因素进行了多元回归分析,为探索原发性肝癌患者GR降低与肝癌发病及治疗的关系提供了初步的实验依据。在后续工作中,我们将继续随访观察患者的生存期及生存质量等指标,对糖皮质激素及其受体水平高低与肝癌发展之间关系进行探讨,也将继续研究对原发性肝癌患者应用糖皮质激素的治疗作用及预防复发作用的意义。更多还原

【Abstract】 Investigation background:Heptocellular carcinoma is one of common malignant tumors in our country, which seriously jeopardize people’s health. So far, there has been almost no effectual therapeutic drug except to adopt various of operative measures yet. It has intimate relation between glucocorticoid and tumour, the previons research reports that glucocorticoid can inhibit proliferation and induce apoptosis of hepatoma carcinoma cell, inhibiting proliferation and inducing cell differentiation of human ovarian cancer. Besides, glucocorticoid may be involved in inhibiting proliferation on human breat cancer cell lines cell, and inhibit the growth of vascular endothelial factor of tumour cell. Glucocorticoid receptor is important to signal conduction of tumour cell and the related gene of tumour and apoptosis, so it has been paid great attention the relation between GR and tumour. Ho,et al. observed that GR is discovered in the cytoplasm of majority primary hepatic carcinoma patient, which is the independently prognosis factor after primary hepatic carcinoma carcinosectomy. the survival rate of GR masculine is lower than GR negative. It is found that the GR content in tumor of liver is different. Most writer find that the GR content is descend in patient of cirrhosis of liver, while the GR content is increased in the hepatic cellular cancer. We need make a deep study on the relationship between GC and its receptor and the treatment and prognosis in primary hepatic carcinoma.Objective: To investigate the variation and mechanisms of effect on the glucocorticoid and it’s glucocorticoid receptor (GR) of primary hepatic carcinoma patients.Methods:1. there are two group, one is consisted of 79 people who are primary hepatic carcinoma patients and the other group is consisted of 66 healthy people. We phlebotomize at six in the morning, then we separate blood serum and detect the glucocorticoid level by radioimmunity method.2. They are devided into primary hepatic carcinoma patients group and healthy people group, each group contains 22 persons. We phlebotomize at six in the morning, and detect the GR content with flow cytometry and observe the change of the glucocorticoid receptor (GR) content in primary hepatic carcinoma patients with 13 people after traditional Chinese drug combined therapy in our department.Results:1 .The glucocorticoid in primary hepatic carcinoma patients is lower by(P<0.05) than in the healthy people, the glucocorticoid is related to potassium, serum hepatitis and creatinine,extremely largest inverse correlation with the serum hepatitis, the interrelated coefficient is—44.484. the glucocorticoid is related to creatinine, gender and ALT in healthy adult, the glucocorticoid is lower in the female people than in the male people, the interrelated coefficient is—62.747.the glucocorticoid is elevated after treatment of the traditional Chinese medicine in primary hepatic carcinoma patients (P<0.01).2. The GR in primary hepatic carcinoma patients is lower by(P<0.01) than in healthy people. The GR combining power fluorescence in primary hepatic carcinoma patients is higher by(P<0.01) than in the health adult. The GR in primary hepatic carcinoma patients is elevated after treatment by(P<0.01).There is no discrepancy of GR combining power in primary hepatic carcinoma patients before and after treatment (P>0.5).Conclusion:1. The glucocorticoid in primary hepatic carcinoma patients is decreased and serum hepatitis is possiblly an important factor for glucocorticoid decreasing.2. The GR of primary hepatic carcinoma patients is lower than that in the healthy people, and the possible reason maybe that (1) cirrhosis of liver, (2) hepatic carcinoma lead to the damage of liver function, (3) the GR combining power is elevated in primary hepatic carcinoma patients, and the reason maybe that the GR decreasing lead to the GR combining power heighting.3. The GC and its receptor of primary hepatic carcinoma is changed obviously after combined therapy of traditional Chinese medicine. It reveals that influencing the GC and its receptor maybe an important effective target of curative effect of traditional Chinese medicine. But conclusive therapeutic action need be confirmed by detecting to correlated index of patient and following visiting duration and quality of life.Prospect:We initially detect the GC, its receptor primary hepatic carcinoma and GR combining power in this reseach and analysize the correlated patho-factors in multiple regression analysis, providing initially experimental data for exploring the relation between GR loss, invasion and therapy in primary hepatic carcinoma patients. In post-work, we will continue to flup and observe the duration and living quality et al indexs of the patient, approach the relationship between GC and its receptor level and development of hepatoma, and study the meaning of therapeutic action and prophylaxis relapse after applicating GC.更多还原