CAJ | 학술논문

目的:观察福辛普利(fosinopril)和氯沙坦(losartan)对自发性高血压大鼠(SHR)肾脏Klotho表达及氧化应激的影响,探讨其对高血压肾损伤的保护作用机制.方法:15只22周龄雄性SHR,随机分为3组(5只/组);模型组(SHR组),福辛普利组[10 mg/(kg·d)],氯沙坦组[50 mg/(kg·d)];以22周龄雄性Wistar-Kyoto(WKY)大鼠5只为正常对照,共喂养8周.检测尾动脉收缩压、24 h尿蛋白定量(Upro)、尿N-乙酰-8-D-氨基葡萄糖苷酶(NAG酶)等指标.HE染色观察大鼠肾脏病理改变,RT-PCR、免疫组织化学及Western印迹检测Klotho蛋白及 mRNA表达;并检测肾脏总抗氧化能力(T-AOC)、丙二醛(MDA)、铜锌超氧化物歧化酶(Cu/Zn-SOD)、锰超氧化物歧化酶(Mn-SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)水平.结果:模型组肾脏出现高血压肾损伤的病理特征.与模型组比较,福辛普利或氯沙坦组收缩压、Upro及尿NAG酶均明显降低,肾脏病理损伤减轻(P<0.05).肾脏Klotho蛋白及mRNA表达均明显上调(P<0.05),同时肾脏MDA含量降低,T-AOC,Cu/Zn-SOD,CAT及GSH-Px活性均较模型组增加(P<0.05 或P<0.01),Mn-SOD活性无明显改变(P>0.05).结论:福辛普利、氯沙坦可通过上调抗衰老基因Klotho在肾脏中的表达,并抑制氧化应激,从而对高血压肾损伤起保护作用.
목적:관찰복신보리(fosinopril)화록사탄(losartan)대자발성고혈압대서(SHR)신장Klotho표체급양화응격적영향,탐토기대고혈압신손상적보호작용궤제.방법:15지22주령웅성SHR,수궤분위3조(5지/조);모형조(SHR조),복신보리조[10 mg/(kg·d)],록사탄조[50 mg/(kg·d)];이22주령웅성Wistar-Kyoto(WKY)대서5지위정상대조,공위양8주.검측미동맥수축압、24 h뇨단백정량(Upro)、뇨N-을선-8-D-안기포도당감매(NAG매)등지표.HE염색관찰대서신장병리개변,RT-PCR、면역조직화학급Western인적검측Klotho단백급 mRNA표체;병검측신장총항양화능력(T-AOC)、병이철(MDA)、동자초양화물기화매(Cu/Zn-SOD)、맹초양화물기화매(Mn-SOD)、과양화경매(CAT)화곡광감태과양화물매(GSH-Px)수평.결과:모형조신장출현고혈압신손상적병리특정.여모형조비교,복신보리혹록사탄조수축압、Upro급뇨NAG매균명현강저,신장병리손상감경(P<0.05).신장Klotho단백급mRNA표체균명현상조(P<0.05),동시신장MDA함량강저,T-AOC,Cu/Zn-SOD,CAT급GSH-Px활성균교모형조증가(P<0.05 혹P<0.01),Mn-SOD활성무명현개변(P>0.05).결론:복신보리、록사탄가통과상조항쇠로기인Klotho재신장중적표체,병억제양화응격,종이대고혈압신손상기보호작용.
Objective To explore effects of fosinopril and losartan on renal Klotho expression and oxidative stress in spontaneously hypertensive rats (SHR) and the mechanisms underlying the protection against renal damage. Methods Fifteen male SHRs (22 weeks old) were randomly divided into 3 groups (n=5 in each group): a SHR group, a fosinopril group ［10 mg/(kg?d)］, and a losartan group ［50 mg/(kg?d)］. Age-matched Wistar-Kyoto (WKY) rats were chosen for a control group. Eight weeks later, tail arterial pressure, 24 hours urinary protein (Upro)，urinary N-acetyl-β-D-glucosaminidase (NAGase) were measured. Renal pathological changes were examined under light microscopy by HE staining. The renal mRNA and protein expression of Klotho were determined by RT-PCR, immunohistochemical staining or Western blot. The levels of total antioxidant capacity (TAOC), malondialdehyde (MDA), Cu/Zn superoxide dismutase (Cu/Zn-SOD), Mn superoxide dismutase (Mn-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined.Results The typical pathological characteristics of hypertensive renal damage were observed in the kidney of the SHR group．Compared with the SHR group, the systolic pressure, Upro, and urinary NAGase, the content of MDA and renal pathological damage was reduced while the renal Klotho expression and activities of TAOC, Cu/Zn-SOD, CAT, and GSH-Px were increased (P<0.05 or P<0.01) in the fosinopril or losartan group. There was no significant difference in renal Mn-SOD level among the 4 groups (P>0.05). Conclusion Fosinopril and losartan can exert protection against hypertensive renal damage through upregulating Klotho expression as well as reducing oxidative stress.