中华肾脏病杂志
中華腎髒病雜誌
중화신장병잡지
2013年
9期
692-697
,共6页
王雁飞%刘丽秋%刘桂美%黄俊彦%季文萱
王雁飛%劉麗鞦%劉桂美%黃俊彥%季文萱
왕안비%류려추%류계미%황준언%계문훤
糖尿病肾病%氧化性应激%脂质过氧化作用%普罗布考%4羟基壬烯醛
糖尿病腎病%氧化性應激%脂質過氧化作用%普囉佈攷%4羥基壬烯醛
당뇨병신병%양화성응격%지질과양화작용%보라포고%4간기임희철
Diabetic nephropathies%Oxidative stress%Lipid peroxidation%Probucol%4-hydroxynonenal
目的 观察链脲菌素(STZ)诱导的糖尿病大鼠肾小球中4羟基壬烯醛(4-HNE)的表达,并探讨普罗布考的肾脏保护作用机制.方法 60 mg/kg STZ一次性腹腔注射构建糖尿病大鼠模型,造模成功后按随机数字表法分为糖尿病组(D组,n=24)和普罗布考干预组(P组,n=24),同时选取健康大鼠作为正常对照组(C组,n=24).P组大鼠给予普罗布考110mg· kg-1·d-1灌胃,D组及C组给予相等体积蒸馏水灌胃.分别于4周、8周及12周检测24 h尿蛋白量、血清胆固醇、三酰甘油、尿素氮及血肌酐.HE染色及PAS染色后光镜下观察肾脏病理变化,免疫组化观察肾组织4-HNE的表达,Western印迹检测4-HNE的表达水平.结果 D组24 h尿蛋白量、三酰甘油、胆固醇、尿素氮及肌酐在4周、8周及12周逐渐升高,且均高于同时间的C组,差异有统计学意义(均P< 0.05),P组以上指标均低于同时间的D组,差异有统计学意义(均P< 0.05).P组及D组4周、8周及12周的肾脏病理改变逐渐加重,同时间的P组肾脏病理改变较D组轻,但仍重于C组.D组4周、8周及12周肾脏中的4-HNE的表达均显著高于C组,免疫组化染色积分差异有统计学意义(P< 0.05),P组4-HNE的表达量低于同时间的D组,差异亦有统计学意义(P< 0.05);Western印迹结果与免疫组化结果相符.结论 STZ诱导的糖尿病大鼠肾小球中脂质过氧化标志物4-HEN明显升高,而普罗布考可能通过减少4-HNE的生成减轻脂质过氧化损伤,从而起到肾脏保护作用.
目的 觀察鏈脲菌素(STZ)誘導的糖尿病大鼠腎小毬中4羥基壬烯醛(4-HNE)的錶達,併探討普囉佈攷的腎髒保護作用機製.方法 60 mg/kg STZ一次性腹腔註射構建糖尿病大鼠模型,造模成功後按隨機數字錶法分為糖尿病組(D組,n=24)和普囉佈攷榦預組(P組,n=24),同時選取健康大鼠作為正常對照組(C組,n=24).P組大鼠給予普囉佈攷110mg· kg-1·d-1灌胃,D組及C組給予相等體積蒸餾水灌胃.分彆于4週、8週及12週檢測24 h尿蛋白量、血清膽固醇、三酰甘油、尿素氮及血肌酐.HE染色及PAS染色後光鏡下觀察腎髒病理變化,免疫組化觀察腎組織4-HNE的錶達,Western印跡檢測4-HNE的錶達水平.結果 D組24 h尿蛋白量、三酰甘油、膽固醇、尿素氮及肌酐在4週、8週及12週逐漸升高,且均高于同時間的C組,差異有統計學意義(均P< 0.05),P組以上指標均低于同時間的D組,差異有統計學意義(均P< 0.05).P組及D組4週、8週及12週的腎髒病理改變逐漸加重,同時間的P組腎髒病理改變較D組輕,但仍重于C組.D組4週、8週及12週腎髒中的4-HNE的錶達均顯著高于C組,免疫組化染色積分差異有統計學意義(P< 0.05),P組4-HNE的錶達量低于同時間的D組,差異亦有統計學意義(P< 0.05);Western印跡結果與免疫組化結果相符.結論 STZ誘導的糖尿病大鼠腎小毬中脂質過氧化標誌物4-HEN明顯升高,而普囉佈攷可能通過減少4-HNE的生成減輕脂質過氧化損傷,從而起到腎髒保護作用.
목적 관찰련뇨균소(STZ)유도적당뇨병대서신소구중4간기임희철(4-HNE)적표체,병탐토보라포고적신장보호작용궤제.방법 60 mg/kg STZ일차성복강주사구건당뇨병대서모형,조모성공후안수궤수자표법분위당뇨병조(D조,n=24)화보라포고간예조(P조,n=24),동시선취건강대서작위정상대조조(C조,n=24).P조대서급여보라포고110mg· kg-1·d-1관위,D조급C조급여상등체적증류수관위.분별우4주、8주급12주검측24 h뇨단백량、혈청담고순、삼선감유、뇨소담급혈기항.HE염색급PAS염색후광경하관찰신장병리변화,면역조화관찰신조직4-HNE적표체,Western인적검측4-HNE적표체수평.결과 D조24 h뇨단백량、삼선감유、담고순、뇨소담급기항재4주、8주급12주축점승고,차균고우동시간적C조,차이유통계학의의(균P< 0.05),P조이상지표균저우동시간적D조,차이유통계학의의(균P< 0.05).P조급D조4주、8주급12주적신장병리개변축점가중,동시간적P조신장병리개변교D조경,단잉중우C조.D조4주、8주급12주신장중적4-HNE적표체균현저고우C조,면역조화염색적분차이유통계학의의(P< 0.05),P조4-HNE적표체량저우동시간적D조,차이역유통계학의의(P< 0.05);Western인적결과여면역조화결과상부.결론 STZ유도적당뇨병대서신소구중지질과양화표지물4-HEN명현승고,이보라포고가능통과감소4-HNE적생성감경지질과양화손상,종이기도신장보호작용.
Objective To investigate the expression of 4-hydroxynonenal (4-HNE) in the kidney of diabetic rats and the effect of probucol.Methods The rats were being intraperitoneal injected with STZ (60 mg/kg) to establish diabetic models.Then diabetic rats were randomly divided into diabetic group (group D,n =24),probucol treated group (group P,n =24).Normal rats were taken as control group (group C,n =24).Rats in group P were treated by probucol (110 mg·kg-1·d-1); rats in group D and group C were given equal volume water instead.Scr,BUN,triglyceride (TG),total cholesterol (TC) and 24-hour urinary proteinin were measured at the 4th,8th and 12th week.PAS staining and HE staining were used to evaluate the pathological changes of the kidney.The immunohistochemistry and Western blotting were used to detect the expression of 4-HNE in renal tissue.Results Levels of Scr,BUN,TG,TC and 24-hour urinary protein in group D were higher than those in group C at the 4th,8th and 12th week(all P < 0.05); Levels of Scr,BUN,TG,TC and 24-huor urinary protein in group P were lower than those in group D at 4th,8th and 12th week (all P < 0.05).The pathological changes of the kidney in group D were more serious than that in group P.The expression of 4-HNE in group D were higher than group C at the 4th,8th and 12th week (all P < 0.05);The expression of 4-HNE in the kidneys of group P decreased significantly compared to that of group D at the same time (P < 0.05).Conclusions As an indicator of lipid peroxidation,the expression of 4-HNE significantly increases in the kidney of diabetic rat.Probucol may protect the diabetic kidney through decreasing the expression of 4-HNE and the level of lipid peroxidation.