【作者】 李颖；

【导师】 于建宪；

【作者基本信息】 青岛大学 ， 病理与病理生理学， 2008， 硕士

【摘要】 目的检测瘦素（leptin）及其受体（ob-R）在原发性肝癌中的表达及及意义,以CD34标记血管内皮计数微血管密度（MVD₁）,以CD105标记新生血管内皮计数微血管密度（MVD₂）,探讨瘦素及其受体在肝癌血管生成中的作用;并检测Ki67在肝癌组织及癌旁组织中表达的差异,以了解瘦素及其受体在肝癌细胞增殖方面有无作用。方法应用免疫组化PV9000法检测76例肝癌组织及53例癌旁组织制成的组织芯片中leptin及其受体的表达、并计数肿瘤内微血管密度MVD₁、MVD₂、及细胞核增殖抗原Ki67。对所得结果应用SPSS11.0统计分析软件包进行分析。结果在肝癌组织中leptin表达强阳性12例,占15.79%,中等阳性10例,占13.16%,弱阳性46例,占60.53%。在53例癌旁组织中46例表达为中等阳性或强阳性（86.79%）,弱阳性7例。同时leptin的表达在肝癌组织中与在癌旁组织中有显著性差异（x²=44.58,p＜0.05）,,leptin的表达在肝癌组织中与在正常解剖肝组织中也有显著性差异（x²=30.92,P＜0.05）。在肝癌组织中ob-R表达强阳性17例,占22.36%,中等阳性22例,占28.95%,弱阳性27例,占35.53%。在53例癌旁组织中44例表达为中等阳性或强阳性（83.02%）,弱阳性8例（15.09%）,阴性1例。ob-R的表达在肝癌组织中与在癌旁组织中有显著性差异（x²=18.55,p＜0.05）,ob-R的表达在肝癌组织中与在解剖组织中有显著性差异（x²=9.72,p＜0.05）。leptin蛋白在肝癌组织中表达与患者的年龄、肿瘤直径大小、临床伴随疾病、分化程度等均无统计学意义,且差异无显著性（P＞0.05）;与患者的性别有统计学意义（x²=119.92,p＜0.05）。ob-R蛋白在肝癌组织中表达与患者的年龄、肿瘤直径大小、临床伴随疾病、分化程度等均无统计学意义,且差异无显著性（P＞0.05）;也与患者的性别有统计学意义（x²=144,P＜0.05）。肝癌组织中leptin表达与MVD₁呈负相关关系（r=-0.323,p＜0.05）。同时肝癌组织中leptin表达与MVD₂两者之间也呈负相关关系（r=-0.309,p＜0.05）。MVD₂表达明显低于MVD₁,且两者之间有显著性差异（t=-3.746,p＜0.05）。在肝癌细胞中leptin表达与Ki67表达呈负相关关系（r=-0.282,p＜0.05）。Ki67表达在肝癌细胞明显高于在癌旁组织中,且两者之间有显著性差异（t=10.683,p＜0.05）。结论（1）HCC中leptin及ob-R的表达均明显低于在癌旁组织中的表达,提示leptin及ob-R在原发性肝细胞肝癌的发生、发展上有一定的抑制作用。（2）HCC中leptin及ob-R的表达均与肝癌患者的年龄、临床伴随疾病、肿瘤的大小以及分化程度均无明显关系,而与患者的性别有显著的统计学意义,表明性别影响leptin及ob-R在肝癌组织的表达水平。（3）HCC中MVD₁、MVD₂表达与leptin的表达呈负相关关系,MVD₂均值明显小于MVD₁,且两者的表达与在癌旁组织中的表达有显著性差异,推测leptin可能抑制肝癌细胞的血管生成。（4）HCC中Ki67的表达与leptin的表达呈负相关关系,其在肝癌组织中的表达与在癌旁组织中的表达有显著性差异,表明leptin可通过某种途径抑制肝癌细胞的增殖。更多还原

【Abstract】 OBJECTIVE To detect the expression and significance of leptin and ob-R in PHC, meanwhile to contrast MVD₁（representing CD34） and MVD₂（representing CD105） for investigating the role of leptin and its receptor in angiogenesis in hepatoma;To detect the distinction of expression of ki67 between hepatoma and paracarcinoma tissue and to investigate the role of leptin and its receptor in proliferation in hepatoma.METHOD The expression ofleptin and its receptor、CD34、CD105 andKi67 in 76 cases hepatoma,53 cases paracarcinoma tissue were examined by immunohistochemistry PV9000 and tissue microarray technique,and by SPSS 11.0 statistical analysis package analyze the results.RESULTS 12 strong positive cases（accounting 22.36%）,22 moderate cases （accounting 28.95%）,27 weakly cases（accounting 35.53%） of leptin in 76 cases of heptoma;46 strong and moderate cases（accounting 86.79%）、7 weakly cases in 53 cases paracarcinoma tissue.Meanwhile the expression of leptin represented predominant discrepancy between cancer and paracarcinoma tissue（x²=44.58,p＜0.05）.The expression of ob-R was 17 strong positive cases（accounting 22.36%）,22 moderate cases（accounting 28.95%） and 27 weakly cases（accounting 35.53%） in hepatoma.Meanwhile the expression of ob-R represented predominant discrepancy between cancer and paracarcinoma tissue（x²= 18.55,p＜0.05）.The expression of leptin in hepatoma had no statistical significance with acromegalic ages、tumor’s diameter,clinic accompaniment diseases,differentiated degree and the discrepancy represented no significant（P＞0.05）;But it represented statistical significance with patient’s gender（x² = 119.92 p＜0.05）.The expression of ob-R in hepatoma had no statistical significance with patient’s ages、tumor’s diameter、clinic accompaniment diseases,defficientiated degree and the discrepancy represented no significant（P＞0.05）;But it represented statistical significance with patient’s gender（x²= 144,P＜0.05）.The express intension of between leptin and MVD₁ represented negatively correlation（r=-0.323,p＜0.05）,so as MVD₂（r=-0.309,p＜0.05）.The expression of MVD₂ was weaker than the expression of MVD₁,at the same time they represented significant difference between them（t=3.746,p＜0.05）.The express intension of between leptin and ki67 represented negatively correlation（r=-0.282,p＜0.05）.CONCLUSION The expressions of leptin and ob-R in HCC were all weaker than that in paracarcinoma tissues,it indicated that leptin and ob-R may have determinated inhibitory action in carcinogenesis and development of HCC.The expression of leptin and ob-R in HCC had no obviously relationship with patient’s ages、tumor’s diameter、clinic accompaniment diseases、differentiated degree,but had pridominent statistical significance with acromegalic gender.,it indicated that gender may affect the express level of leptin and ob-R in hepatoma.The expression of MVD₁ and MVD₂ represented negatively correlation with the express intension of leptin and the expression of MVD₂ was weaker than the expression of MVD₁,these indicated leptin may inhibit the angiogenesis of hepatomilia cell.The expression of ki67 represented negatively correlation with increasing for the express intension of leptin between HCC and paracarcinoma tissue,these indicated leptin may inhibit the proliferation ofhepatomilia cell by some kind of pathway.更多还原