洛沙坦对人类卵巢癌裸鼠模型腹水的抑制作用  

Inhibition by Losartan on ascites in a nude mouse model of human ovarian cancer

作　　者：曹京红[1] 翟建军[1] Cao Jinghong;Zhai Jianjun(Department of Obstetrics and Gynecology,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China)

机构地区：[1]首都医科大学附属北京同仁医院妇产科,北京100730

出　　处：《中华老年医学杂志》2020年第2期209-213,共5页Chinese Journal of Geriatrics

摘　　要：目的研究洛沙坦是否可以通过改善淋巴引流抑制卵巢癌裸鼠模型腹水的形成。方法8周龄雌性裸鼠,随机分3组,每组24只鼠。空白对照组不给予任何处理。另两组给予原位移植SKOV3 IP1-Gluc卵巢癌细胞,根据外周血Gluc水平监测腹腔内肿瘤生长情况,达到1×106相对光单位时入组。对照组为卵巢癌无治疗组,22只鼠入组,卵巢癌洛沙坦治疗组23只鼠入组。注射肿瘤后第28天处死,取出腹腔内肿瘤及膈肌,抽吸腹水测量。免疫组化方法检测sirius red、αSMA、Collagen 1,了解细胞外基质胶原蛋白及纤维母细胞含量。用淋巴管造影方法观察膈肌淋巴管形态,腹腔内注射荧光微球观察膈肌及纵膈淋巴结荧光微球分布情况,了解膈肌淋巴管引流功能。结果洛沙坦治疗可以明显减少卵巢癌裸鼠模型腹水形成(P<0.05)。洛沙坦治疗组肿瘤内胶原蛋白含量(sirius red阳性区域,Collagen 1含量)及纤维母细胞(αSMA阳性区域)均明显减少(均P<0.05)。与正常裸鼠比较,卵巢癌无治疗组裸鼠膈肌淋巴管扩张,结构紊乱;洛沙坦治疗组裸鼠膈肌淋巴管形态和分布情况改善,趋于正常化,而淋巴管引流功能也得到明显改善。结论洛沙坦可以抑制细胞外基质形成,减少卵巢癌细胞外基质含量,降低固态压力,解除对淋巴管的压迫作用,改善淋巴引流,减少腹水形成,使临床获益。Objective To investigate whether Losartan can inhibit the formation of ascites in a nude mouse model of ovarian cancer by improving lymphatic drainage.Methods Eight-week-old nude mice were randomly divided into 3 groups with 24 mice in each group.The blank control group received no treatment.Mice in the other two groups were given orthotopic transplantation of SKOV3 IP1-Gluc human ovarian cancer cells.Peritoneal tumor growth was monitored by peripheral blood Gluc levels,and mice were enrolled when the blood Gluc level reached 1×106 relative light units.Twenty-two nude mice were in the control group and 23 in the Losartan treatment group.Mice were sacrificed on the 28th day after cancer cell implantation.Tumor tissues and diaphragm were removed,and the volume of ascites was measured after suction.Sirius Red,αSMA and Collagen 1 staining were used to detect the contents of extracellular matrix collagen and fibroblasts.Lymphangiography was used to examine the diaphragmatic lymphatic morphology,and intraperitoneal injection of fluorescent microspheres was used to visualize the distribution of fluorescent microspheres in diaphragmatic and mediastinal lymph nodes to estimate the function of diaphragmatic lymphatic drainage.Results Losartan treatment significantly reduced the formation of ascites in the nude mouse model of ovarian cancer(P<0.05).Intratumoral contents of collagen(sirius red positive area,Collagen 1 content)and fibroblasts(αSMA positive area)were significantly reduced in the Losartan treatment group(all P<0.05).Compared with normal nude mice,the diaphragm lymphatic vessels were dilated and the structure was disordered in the control group.In the Losartan treatment group,the morphology and distribution of lymphatic vessels in the diaphragm improved and tended to normalize,as did the drainage function of lymphatic vessels.Conclusions Losartan can inhibit the formation of extracellular matrix,reduce the extracellular matrix content of ovarian cancer cells,reduce solid pressure,relieve the oppressive effect

关 键 词：洛沙坦 卵巢肿瘤 受体 血管紧张素 

分 类 号：R737[医药卫生—肿瘤] R-332[医药卫生—临床医学]