乌司他丁对肾血管性高血压大鼠肾损害及肾组织一氧化氮/内皮型一氧化氮合酶通路的影响  

Effects of Ulinastatin on Blood Pressure and Nitric Oxide/Endothelial Nitric Oxide Synthase Pathway in Renal Tissues of Renovascular Hypertensive Rats

作　　者：周桔丰 张瑞城 Zhou Jufeng;Zhang Ruicheng(Department of Clinical Nutrition;Department of Nephrology,the First Affiliated Hospital ofHainan Medical College,Haikou 570102,China)

机构地区：[1]海南医学院第一附属医院临床营养科,海口570102 [2]海南医学院第一附属医院肾内科,海口570102

出　　处：《中国药师》2019年第7期1227-1231,共5页China Pharmacist

基　　金：海南省卫生计生行业科研项目(编号:14A200065)

摘　　要：目的:探讨乌司他丁对肾血管性高血压(RH)大鼠血压及其对肾组织一氧化氮(NO)/内皮型一氧化氮合酶(e NOS)通路的影响。方法:将60只大鼠随机分为6组:正常对照组、模型组、阳性对照组(卡托普利,30 mg·kg-1)、乌司他丁低(20 000 U·kg-1)、中(40 000 U·kg-1)、高(60 000 U·kg-1)剂量组,每组10只。腹腔注射给药,1次/d,连续给药6周。采用苏木精-伊红(HE)染色法观察大鼠肾损伤病理组织形态;比较各组大鼠肾功能指标24 h尿蛋白定量、血清肌酐(SCr)、尿素氮(BUN)水平;比较分析炎性因子及氧化应激水平;采用酶联免疫吸附法(ELISA)检测肾组织中NO浓度;蛋白免疫印迹(Western blot)法检测肾组织中e NOS蛋白相对表达量。结果:模型组RH大鼠肾组织具有炎细胞浸润及肾小管上皮细胞空泡变性等现象;与模型组相比,阳性对照组与乌司他丁高剂量组RH大鼠肾损伤减轻肾小球毛细血管扩张充血,肾小管腔无明显扩张且上皮细胞空泡变性较少。与正常对照组相比,模型组大鼠白细胞介素-18(IL-18)、白细胞介素-6(IL-6)、丙二醛(MDA)、活性氧簇(ROS)、24 h尿蛋白量、SCr、BUN水平均显著升高,白细胞介素-10(IL-10)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平及NO浓度、e NOS蛋白相对表达量显著降低(P<0.05)。与模型组相比,阳性对照组及乌司他丁不同剂量组IL-18、IL-6、MDA、ROS、24 h尿蛋白量、SCr、BUN水平均显著降低,IL-10、SOD、CAT水平及NO浓度、e NOS蛋白相对表达量显著升高(P<0.05),且乌司他丁呈剂量相关性。乌司他丁中、低剂量组与与阳性对照组差异有统计学意义(P<0.05)。结论:乌司他丁可有效缓解RH大鼠肾损害,其可能是通过激活NO/e NOS通路实现降压作用。Objective: To investigate the effects of ulinastatin on blood pressure and nitric oxide( NO)/endothelial nitric oxide synthase( e NOS) pathway in renal tissues of renovascular hypertension( RH) rats. Methods: Totally 60 rats were randomly divided into 6 groups: the normal control group,the model group,the positive control group( captopril,30 mg · kg-1),ulinastatin low( 20 000 U·kg-1),medium( 40 000 U·kg-1) and high( 60 000 U·kg-1) dose groups,and 10 rats were in each group. Intraperitoneal injection was given once a day for 6 weeks. Hematoxylin-eosin( HE) staining was used to observe the pathological morphology of renal injury in rats. The renal function indices including 24 h urine protein quantitation,serum creatinine( SCr) and urea nitrogen( BUN) levels were compared among the groups. The levels of inflammatory factors and oxidative stress were compared as well. Enzymelinked immunosorbent assay( ELISA) was used to detect the concentration of NO in renal tissues and the relative expressions of e NOS protein in renal tissues was detected by Western blot. Results: The renal tissues of RH model group had inflammatory cells infiltration and vacuolar degeneration of renal tubular epithelial cells. Compared with that in the model group,the renal injury in the positive control group and ulinastatin high dose group reduced the glomerular capillary dilatation and hyperemia,and the renal tubular lumen showed no obvious expansion and the epithelial vacuolar degeneration was less. Compared with those in the normal control group,the rats in the model group had significantly increased interleukin-18( IL-18),interleukin-6( IL-6),malondialdehyde( MDA),reactive oxygen species( ROS),24 h urine protein,SCr and BUN levels,and significantly decreased interleukin-10( IL-10),superoxide dismutase( SOD),catalase( CAT) levels,NO concentration and e NOS protein relative expressions( P< 0.05). Compared with those in the model group,IL-18,IL-6,MDA,ROS,24 h urine protein,SCr and BUN levels were significantly decreased in the positive co

关 键 词：乌司他丁 肾血管性高血压 一氧化氮/内皮型一氧化氮合酶通路 

分 类 号：R965.1[医药卫生—药理学]