睾酮受体蛋白在2K1C大鼠肾脏内的表达水平改变及其机制研究
发布时间：2018-11-28 17:07
【摘要】：背景近年来,随着高血压的发病率逐年上升,高血压靶器官损害越来越受到人们的关注,高血压肾脏损害是高血压常见的靶器官损害之一,其机制不明确。睾酮是机体内重要的雄性激素之一,国内外多项研究已证实其与心血管疾病密切相关。睾酮的生物学活性是通过睾酮受体实现的,睾酮受体(androgen receprtor,AR)表达水平的变化与多种疾病的发生发展相关。但关于其在高血压肾损害中的地位作用及其信号转导机制不清。已知,丝裂素活化蛋白激酶(mitogen-activated protein kinases,MAPKs)是丝/苏氨酸蛋白激酶中的一种,MAPKs的过度激活在高血压肾损害的发生、发展中发挥重要作用。丝裂素活化蛋白酶磷酸酶1(mitogen-activated protein kinase phosphatase-1,MKP-1)是MAPK的特异性调节磷酸酶,可使磷酸化的MAPK失活。国内外多个研究小组发现,AR与MAPKs偶联多种疾病的发生发展。我课题组以往的研究证实,AR可能与MAPKs相偶联共同参与高血压心肌重构的过程。在高血压肾脏损害中,是否也存在有AR的参与?其是否与MAPKs信号转导通路有关,未见相关报道。目的探讨AR在高血压肾脏损害中的作用并初步探讨其作用机制。方法按照随机对照原则将30只28日龄雄性Wistar大鼠分为正常对照组、假手术对照组和高血压组,每组10只。“两肾一夹法”建立左肾动脉狭窄的肾血管性高血压大鼠模型;假手术组仅打开腹腔不做结扎处理;正常对照组无处理。采用Tail-Cuff法测量各组大鼠不同时期尾鼠尾动脉收缩压(systolic blood pressure,SBP);采用苏木精伊红(hematoxylin eosin stain,HE)染色法观察各组大鼠左右肾脏的组织形态结构变化;采用免疫组化法检测三组大鼠右肾组织中AR蛋白及MKP-1蛋白的表达水平。结果1.正常对照组大鼠SBP无明显变化(P0.05),左右肾脏组织形态大致正常;2.假手术对照组大鼠SBP无明显变化(P0.05),左右肾脏形态学观察无明显改变;与正常对照组相比,假手术对照组右肾组织中AR及MKP-1蛋白表达水平无明显变化(P0.05);3.高血压组大鼠造模后SBP明显增高(F组间=1211.779,F时间=1613.225,F交互=1537.050,P0.001);与正常对照组相比,高血压组大鼠右肾重构;与正常对照组相比,高血压组大鼠右肾组织中AR和MKP-1蛋白表达水平明显下降(P0.001);4.在高血压组大鼠右肾组织中AR与MKP-1蛋白表达水平的呈线性正相关(r=0.744,P=0.014),在正常对照组和假手术对照组无明显相关(r=0.457和0.436,P0.05)结论1.高血压肾脏损害过程中存在AR蛋白表达水平的改变。2.AR蛋白可能与MAKPs信号转导通路相偶联共同参与高血压肾脏损害的过程。
[Abstract]:Background in recent years, with the incidence of hypertension rising year by year, hypertension target organ damage has attracted more and more attention. Hypertensive kidney damage is one of the common target organ damage in hypertension, and its mechanism is unclear. Testosterone is one of the most important androgens in the body. Many studies at home and abroad have proved that testosterone is closely related to cardiovascular disease. The biological activity of testosterone is realized by testosterone receptor. The change of testosterone receptor (androgen receprtor,AR) expression level is related to the occurrence and development of many diseases. However, its role in hypertensive renal damage and its signal transduction mechanism are unclear. It is known that mitogen-activated protein kinase (mitogen-activated protein kinases,MAPKs) is one of the mitogen / threonine protein kinases. Excessive activation of MAPKs plays an important role in the pathogenesis and development of hypertensive renal damage. Mitogen-activated protease 1 (mitogen-activated protein kinase phosphatase-1,MKP-1) is a phosphatase specifically regulated by MAPK, which inactivates phosphorylated MAPK. Many research groups at home and abroad have found that AR is coupled with MAPKs in the occurrence and development of many diseases. Our previous studies have confirmed that AR may be coupled with MAPKs in the process of hypertensive myocardial remodeling. Is there any involvement of AR in hypertensive kidney damage? Whether it is related to MAPKs signal transduction pathway has not been reported. Objective to investigate the role of AR in hypertensive renal damage and its mechanism. Methods Thirty 28 day old male Wistar rats were randomly divided into normal control group, sham operation control group and hypertension group with 10 rats in each group. The rat model of renal vascular hypertension with left renal artery stenosis was established by "two kidneys and one clip method", the sham operation group only opened the abdominal cavity without ligation, and the normal control group did not. The systolic blood pressure (systolic blood pressure,SBP) of caudal artery was measured by Tail-Cuff method and the changes of left and right kidneys were observed by hematoxylin eosin (hematoxylin eosin stain,HE) staining. The expression of AR protein and MKP-1 protein in the right kidney of the three groups were detected by immunohistochemical method. Result 1. There was no significant change in SBP in normal control group (P0.05), and left and right renal tissue morphology was approximately normal; 2. There were no significant changes in SBP and left and right kidney morphology in sham-operated control group (P0.05). Compared with normal control group, the expression of AR and MKP-1 protein in right kidney of sham-operated control group had no significant change (P0.05). 3. The SBP of the hypertensive group was significantly higher than that of the normal control group (F = 1211.779F = 1613.225F interaction = 1537.050p 0.001), and the right renal remodeling in the hypertensive group was significantly higher than that in the normal control group. Compared with the normal control group, the expression of AR and MKP-1 protein in the right kidney of hypertensive rats decreased significantly (P0. 001); 4. There was a linear positive correlation between the expression of AR and MKP-1 protein in the right kidney tissue of hypertensive rats (r = 0.744), but there was no significant correlation between normal control group and sham operation control group (r = 0.457 and 0.436P 0.05). Conclusion 1. There is a change in the expression of AR protein during renal injury in hypertension. 2.AR protein may be coupled with MAKPs signal transduction pathway to participate in the process of hypertensive renal damage.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692;R544.1
本文编号：2363635
[Abstract]:Background in recent years, with the incidence of hypertension rising year by year, hypertension target organ damage has attracted more and more attention. Hypertensive kidney damage is one of the common target organ damage in hypertension, and its mechanism is unclear. Testosterone is one of the most important androgens in the body. Many studies at home and abroad have proved that testosterone is closely related to cardiovascular disease. The biological activity of testosterone is realized by testosterone receptor. The change of testosterone receptor (androgen receprtor,AR) expression level is related to the occurrence and development of many diseases. However, its role in hypertensive renal damage and its signal transduction mechanism are unclear. It is known that mitogen-activated protein kinase (mitogen-activated protein kinases,MAPKs) is one of the mitogen / threonine protein kinases. Excessive activation of MAPKs plays an important role in the pathogenesis and development of hypertensive renal damage. Mitogen-activated protease 1 (mitogen-activated protein kinase phosphatase-1,MKP-1) is a phosphatase specifically regulated by MAPK, which inactivates phosphorylated MAPK. Many research groups at home and abroad have found that AR is coupled with MAPKs in the occurrence and development of many diseases. Our previous studies have confirmed that AR may be coupled with MAPKs in the process of hypertensive myocardial remodeling. Is there any involvement of AR in hypertensive kidney damage? Whether it is related to MAPKs signal transduction pathway has not been reported. Objective to investigate the role of AR in hypertensive renal damage and its mechanism. Methods Thirty 28 day old male Wistar rats were randomly divided into normal control group, sham operation control group and hypertension group with 10 rats in each group. The rat model of renal vascular hypertension with left renal artery stenosis was established by "two kidneys and one clip method", the sham operation group only opened the abdominal cavity without ligation, and the normal control group did not. The systolic blood pressure (systolic blood pressure,SBP) of caudal artery was measured by Tail-Cuff method and the changes of left and right kidneys were observed by hematoxylin eosin (hematoxylin eosin stain,HE) staining. The expression of AR protein and MKP-1 protein in the right kidney of the three groups were detected by immunohistochemical method. Result 1. There was no significant change in SBP in normal control group (P0.05), and left and right renal tissue morphology was approximately normal; 2. There were no significant changes in SBP and left and right kidney morphology in sham-operated control group (P0.05). Compared with normal control group, the expression of AR and MKP-1 protein in right kidney of sham-operated control group had no significant change (P0.05). 3. The SBP of the hypertensive group was significantly higher than that of the normal control group (F = 1211.779F = 1613.225F interaction = 1537.050p 0.001), and the right renal remodeling in the hypertensive group was significantly higher than that in the normal control group. Compared with the normal control group, the expression of AR and MKP-1 protein in the right kidney of hypertensive rats decreased significantly (P0. 001); 4. There was a linear positive correlation between the expression of AR and MKP-1 protein in the right kidney tissue of hypertensive rats (r = 0.744), but there was no significant correlation between normal control group and sham operation control group (r = 0.457 and 0.436P 0.05). Conclusion 1. There is a change in the expression of AR protein during renal injury in hypertension. 2.AR protein may be coupled with MAKPs signal transduction pathway to participate in the process of hypertensive renal damage.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692;R544.1
【参考文献】
相关期刊论文 前10条
1 朱吉莉;;原发性与肾实质性恶性高血压的临床特点与肾脏病理比较[J];中国中西医结合肾病杂志;2016年10期
2 赵书润;孟琳;;前列腺癌患者血清睾酮水平、前列腺雄激素受体表达与精索静脉曲张相关研究[J];癌症进展;2016年07期
3 管斌亚;屈百鸣;;经导管去肾交感神经术改善心肌重构的研究进展[J];心脑血管病防治;2016年02期
4 杨园园;石翊飒;周海娇;;MKP-1和MKP-3与疼痛关系的研究进展[J];中国疼痛医学杂志;2016年04期
5 郑芳蓉;;高血压肾病患者肾脏病理改变与临床表现的关系[J];航空航天医学杂志;2016年02期
6 李渊;王颖;燕树勋;杨国杰;张彦周;孙丽娜;于超男;杨晓村;;高血压大鼠心肌组织中睾酮受体蛋白的表达[J];郑州大学学报(医学版);2016年01期
7 徐中山;;高血压与交感神经系统的神经源性机制研究进展[J];中西医结合心脑血管病杂志;2015年13期
8 刁小伟;李园;皮玉瑞;李同辉;刘平;卢山;;雄激素依赖性前列腺癌细胞中雄激素受体上调EphA3表达[J];天津医药;2015年11期
9 徐丽爽;韩玉];;雄激素受体基因多态性与多囊卵巢综合征患者高雄激素血症及其表型的相关研究[J];职业与健康;2015年14期
10 汪晓芬;和渝斌;张源波;金婧茹;;高血压发病机制及诊疗研究的新认识[J];中国循证心血管医学杂志;2015年02期
相关博士学位论文 前5条
1 刘璐;性激素受体在BDE47所致肝脏脂质代谢异常性别差异中的作用研究[D];南京医科大学;2016年
2 崔玉倩;睾酮对胰岛β-细胞胰岛素分泌和凋亡的影响及机制[D];山东大学;2012年
3 李霖;雄激素受体在波动性高糖致人脐静脉内皮细胞损伤中的作用及其机制研究[D];浙江大学;2012年
4 梁春红;雄激素、雄激素受及AR基因CAG多态性与冠心病危险因素的相关性研究[D];中国人民解放军军医进修学院;2006年
5 楚新梅;雄激素、雄激素受体水平和AR基因多态性与老年男性高血压及PAOD的相关研究[D];中国人民解放军军医进修学院;2005年
相关硕士学位论文 前3条
1 于超男;睾酮受体蛋白表达水平改变在高血压血管重构中的作用[D];郑州大学;2016年
2 冯昱斌;基于AngⅡ/MAPK通路探讨潜阳育阴颗粒改善高血压肾损害的实验研究[D];南京中医药大学;2015年
3 岳长久;血清睾酮水平、前列腺雄激素受体表达与前列腺癌临床进展之间的研究[D];内蒙古大学;2013年
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