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血管紧张素Ⅱ型受体阻滞剂对妊娠高血压大鼠血红素氧合酶-1和尿蛋白水平的影响

Effects of angiotensinⅡreceptor blocker on heme oxygenase-1 and urine protein levels in rats with pregnancy hypertension.
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摘要 目的探讨血管紧张素Ⅱ型受体阻滞剂对妊娠高血压大鼠血红素氧合酶-1和尿蛋白水平的影响。方法选择50只8~10周龄Sprague Dawley雌性大鼠和雄性大鼠建立妊娠模型大鼠,并通过注射亚硝基左旋精氨酸甲酯建立妊娠高血压模型,然后将36只成模大鼠根据实验目的分为3组:妊娠高血压组、氯沙坦1组、氯沙坦2组,每组各12只。氯沙坦1组、氯沙坦2组分别给予7、14 mg·kg^(-1)·d^(-1)的氯沙坦灌胃,妊娠高血压组给予等体积的蒸馏水灌胃。分别于妊娠第7、14、21天,采用动物无创血压测量仪测量孕鼠尾动脉收缩压,并通过自动生化分析仪定量24 h尿蛋白值;在妊娠第21天,采用酶联免疫吸附试验检测血清肾素、血管紧张素、醛固酮含量,蛋白质印迹法检测血红素氧合酶-1蛋白的相对表达水平。结果妊娠后第14~21天,氯沙坦1组、氯沙坦2组尾动脉收缩压均显著低于妊娠高血压组,氯沙坦2组也显著低于氯沙坦1组,差异均有统计学意义(P<0.05)。妊娠后第14~21天,氯沙坦1组、氯沙坦2组24 h尿蛋白水平均显著低于妊娠高血压组,氯沙坦2组也显著低于氯沙坦1组,差异均有统计学意义(P<0.05)。妊娠第21天,氯沙坦1组、氯沙坦2组血清肾素、血管紧张素、醛固酮含量均低于妊娠高血压组,氯沙坦2组低于氯沙坦1组,差异均有统计学意义(P<0.05)。妊娠第21天,氯沙坦1组、氯沙坦2组胎盘组织血红素氧合酶-1、CyclinB1、p21蛋白相对表达水平高于妊娠高血压组,氯沙坦2组高于氯沙坦1组,差异均有统计学意义(P<0.05)。结论血管紧张素Ⅱ型受体阻滞剂在妊娠高血压大鼠的应用能抑制血红素氧合酶-1、CyclinB1、p21的表达,降低尿蛋白水平,抑制血清肾素、醛固酮、血管紧张素的释放,从而持续发挥降压作用。 Objective To investigate the effects of angiotensinⅡreceptor blocker on heme oxygenase-1 and urine protein levels in rats with pregnancy-induced hypertension.Methods Fifty 8 to 10 week-old Sprague Dawley(SD)female rats and male rats were selected to establish pregnancy model rats,and the pregnancy hypertension model was established by injection of nitroso-L-arginine methyl ester.Then 36 model rats were divided into three groups according to the purpose of the experiment-pregnancy hypertension group,Losartan 1 group and Losartan 2 group,each group 12 rats.Losartan 1 group and Losartan 2 group were given 7 and 14 mg·kg^(-1)·d^(-1) of losartan by gavage respectively,and the pregnancy-induced hypertension group were given an equal volume of distilled water by gavage.On the 7th,14th,and 21st day of pregnancy,the systolic blood pressure of the tail artery of the pregnant rat was measured with an animal non-invasive blood pressure meter,and the 24h urine protein value was quantified by an automatic biochemical analyzer;On the 21st day of pregnancy,the enzyme-linked immunoassay was used to detect the serum renin,angiotensin,and aldosterone levels,and the Western blot method was used to detect the relative expression level of heme oxygenase-1 protein.Results From 14 to 21 days after pregnancy,the systolic blood pressure of the tail artery in the Losartan 1 group and Losartan 2 group were significantly lower than that of the pregnancy-induced hypertension group,and the Losartan 2 group was also significantly lower than Losartan 1 group(P<0.05).From 14 to 21 days after pregnancy,the 24 h urine protein levels of Losartan 1 and Losartan 2 were significantly lower than those of the pregnancy-induced hypertension group,and Losartan 2 was also significantly lower than Losartan group(P<0.05).The levels of serum renin,angiotensin,and aldosterone on the 21st day of pregnancy in losartan group 1 and losartan group 2 were lower than those in the pregnancy-induced hypertension group,and losartan group 2 was lower than losartan Tan
作者 王影 王海丽 樊阳阳 WANG Ying;WANG Hai-li;FAN Yang-yang(Department of Obstetrics,Shaanxi Provincial People's Hospital,Xi'an Shaanxi 710068,China.)
出处 《临床和实验医学杂志》 2021年第15期1582-1585,共4页 Journal of Clinical and Experimental Medicine
基金 陕西省重点研发计划(编号:2020SF-037) 陕西省人民医院科技发展基金(编号:2020YXM-11)。
关键词 大鼠 妊娠高血压 血管紧张素Ⅱ型受体阻滞剂 氯沙坦 血红素氧合酶-1 尿蛋白 Rats Hypertension during pregnancy AngiotensinⅡreceptor blocker Losartan Heme oxygenase-1 Urine protein
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