EGCG对老龄大鼠阴茎组织中PRMT1、DDAH、ADMA、NOS通路的影响  

Effects of EGCG on PRMT1,DDAH,ADMA and NOS pathway in corpus cavernosum of aged rats

作　　者：陈东[1] 马专昌 李博[1] 孙鼎琪[1] 张克勤[1] 张辉[1] 傅强[1] 

机构地区：[1]山东大学附属省立医院泌尿外科,山东济南250021 [2]威海卫人民医院泌尿外科,山东威海264200

出　　处：《山东大学学报（医学版）》2016年第5期17-22,共6页Journal of Shandong University:Health Sciences

摘　　要：目的研究表没食子儿茶素没食子酸酯(EGCG)对老龄大鼠阴茎组织中蛋白质精氨酸甲基转移酶1(PRMT1)、二甲基精氨酸二甲胺水解酶(DDAH)、不对称二甲基精氨酸(ADMA)、一氧化氮合酶(NOS)通路表达的影响,探讨其对改善老龄大鼠勃起功能效果。方法 3月龄雄性SD大鼠10只(青年组),18月龄雄性SD大鼠40只,其中筛选出老龄勃起功能障碍(ED)大鼠30只,随机分为老龄组,小剂量治疗组(10 mg/kg EGCG)和大剂量治疗组(100 mg/kg EGCG),每组各10只。连续EGCG灌胃治疗12周后,测定最大海绵体内压(Max ICP)、平均动脉压(MAP)和Max ICP/MAP,处死各组大鼠取阴茎组织。应用免疫组化和Western blotting法测定大鼠阴茎组织中PRMT1、DDAH和NOS表达。酶联免疫法检测大鼠阴茎组织中ADMA和环磷鸟苷(c GMP)含量。黄嘌呤氧化法测定大鼠阴茎海绵体中超氧化物歧化酶(SOD)活性,硫代巴比妥酸法检测丙二醛(MDA)含量。结果与青年组比较,老龄组Max ICP/MAP降低(P<0.05),SOD活性下降(P<0.05),MDA含量增高(P<0.05),cGMP含量降低(P<0.05),ADMA含量升高(P<0.05),DDAH和NOS蛋白表达量均降低(P<0.05),PRMT1蛋白表达量升高(P<0.05)。与老龄组比较,大、小剂量组治疗可使老龄大鼠Max ICP/MAP升高(P<0.05),SOD活性升高(P<0.05),MDA含量降低(P<0.05),cGMP含量升高(P<0.05),ADMA含量降低(P<0.05),DDAH和NOS蛋白表达量明显升高(P<0.05),PRMT1蛋白表达量降低(P<0.05)。结论 EGCG可以通过其抗氧化作用,在一定程度上调节PRMT1、DDAH、ADMA、NOS通路在老龄大鼠阴茎组织中的表达,改善老龄大鼠勃起功能。Objective To elucidate the effects of epigallocatechin-3-gallate（ EGCG） on protein arginine methyltransferase 1（ PRMT1）,dimethylarginine dimethylaminohydrolases（ DDAH）,asymmetrical dimethylarginine（ ADMA）,and nitric oxide synthase（ NOS） pathway in corpus cavernosum of aged rats,and to investigate the possible mechanisms. Methods A total of 30（ erectile dysfunction） ED rats were screened among 40 18-month-old male SD rats,and randomly divided into the aged group（ n = 10）,small dose group（ daily gavage feedings of EGCG at doses of 10 mg / kg for 12 weeks,n = 10） and large dose group（ daily gavage feedings of EGCG at doses of 100 mg / kg for 12 weeks,n = 10）. Another 10 3-month-old rats served as controls. After 12 weeks,the maximal intracavernous pressure（ Max ICP）,mean arterial blood pressure（ MAP） and Max ICP/MAP were determined. The animals were then sacri-ficed to harvest penis tissues. PRMT1,DDAH and NOS levels were detected with Western blotting and immunohistochemistry. ADMA and cGMP levels were assessed with ELISA. The MDA level and SOD activity were also detected.Results Compared with the control group,the aged group had decreased Max ICP / MAP,DDAH,NOS,cGMP and SOD activity（ all P 0. 05）. Compared with the aged group,small and large dose group had significantly increased Max ICP / MAP,SOD activity,cGMP,DDAH and NOS levels,but decreased MDA,ADMA,and PRMT1（ all P 0. 05）. Conclusion EGCG treatment could ameliorate erectile function in aged rats via upregulating PRMT1,DDAH,ADMA and NOS pathway and inhibiting oxidative stress.

关 键 词：勃起功能障碍 表没食子儿茶素没食子酸酯 不对称二甲基精氨酸 二甲基精氨酸二甲胺水解酶 蛋白质精氨酸甲基转移酶1 

分 类 号：R698.1[医药卫生—泌尿科学]