血管紧张素Ⅱ受体及其信号转导关键酶在宫颈癌中的表达

Expressions of Angiotensin Ⅱ receptor and the key signal transduction enzymes in the cervical cancer

目的 探讨血管紧张素Ⅱ-1型受体（AT1R）和血管紧张素Ⅱ-2型受体（AT2R）及其信号转导关键酶在宫颈癌中的表达。方法 收集2013年3月～2014年2月河南省人民医院及中国医科大学航空总医院手术切除正常宫颈组织47例（对照组）、宫颈上皮内瘤变（CIN）组织36例（CIN组）及65例宫颈癌组织标本（宫颈癌组）。采用实时荧光定量PCR检测AT1R和AT2R mRNA水平;蛋白质印记法检测AT1R和AT2R蛋白表达水平。激活AT1R,测定酪氨酸激酶（PTK）活性;激活AT2R,测定胞浆型磷脂酶A2（cPLA2）活性。结果 与对照组比较,CIN组及宫颈癌组AT1R、AT2R的mRNA水平以及蛋白表达水平均明显升高,差异均有统计学意义（P〈0.05或P〈0.01）。激活AT1R后,CIN组与宫颈癌组的PTK活性与对照组比较均明显升高[（64.00±16.23）,（89.00±20.76）比（50.00±12.16）],差异均有统计学意义（P〈0.05或P〈0.01）;与CIN组比较,宫颈癌组进一步升高（P〈0.05）。激活AT2R后,CIN组和宫颈癌组的cPLA2活性与对照组比较均明显升高[（137.00±19.72）、（181.00±30.83）比（104.00±21.46）],差异均有统计学意义（P〈0.05或P〈0.01）;与CIN组比较,宫颈癌组进一步升高,差异有统计学意义（P〈0.05）。结论 AT1R、AT2R与宫颈癌的发生发展密切相关,有望成为宫颈癌潜在的诊断和治疗靶点。

Objective To investigate the expressions of angiotensin Ⅱ receptor （ATR） and the key signal transduction enzymes in cervical cancer. Methods Uterine cervical tissue specimens from the patients who treated in the Henan Province People＇s Hospital and Aviation General Hospital of China Medical University from March 2013 to February 2014 were collected. There were 47 cases of normal cervix （control group）, 36 cases of cervical intraepithelial neoplasia （CIN group） and 65 cases of cervical cancer （cervical cancer group）. The levels of AT1R and ATER mRNA were detect- ed by real-time quantitative PCR and the protein expressions of AT1R and AT2R were determined by Western blot analysis. The activities of protein tyrosine kinase （PTK） were measured when the ATIR was activated by angiotensin Ⅱ. The activities of cytosolic phospholipase A2 （cPLA2） were detected when the AT2R was activated. Results The levels of AT1R and AT2R mRNA in the CIN group and cervical cancer group were significantly increased compared with the control group. The levels of ATIR and AT2R protein expression in the CIN group and cervical cancer group were signifi- cantly increased compared with the control group （P 〈 0.05 or P 〈 0.01）. The activities of PTK were increased signifi- cantly in the CIN group and cervical cancer group compared with control group [（64.00±16.23） vs （50.00±12.16）, P 〈 0.05; （89.00±20.76） vs （50.00±12.16）, P 〈 0.01]. The activities of ePLA2 were increased significantly in the CIN group and cervical cancer group compared with control group [（137.00±19.72） vs （104.00±21.46）, （181.00±30.83） vs （104.00±21.46）], the differences of two were statistically significant （P 〈 0.05 or P 〈 0.01）, compared with the CIN group, cervi- cal cancer group was further increased, the difference was statistically significant （P 〈 0.05）. Conclusion AT1R and ATER are closely associated with the development of cervical cancer and may become candidate markers for early diag- nosis of cervical cancer and new targets for therapy.