国际内分泌代谢杂志
國際內分泌代謝雜誌
국제내분비대사잡지
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2013年
2期
76-80,封3
,共6页
陈欢%沈洁%李章芳%唐杰龙%朱艳%胡园园
陳歡%瀋潔%李章芳%唐傑龍%硃豔%鬍園園
진환%침길%리장방%당걸룡%주염%호완완
糖尿病%肾小球足细胞%血管紧张素转换酶2%尿微量白蛋白排泄率
糖尿病%腎小毬足細胞%血管緊張素轉換酶2%尿微量白蛋白排洩率
당뇨병%신소구족세포%혈관긴장소전환매2%뇨미량백단백배설솔
Diabetes mellitus%Glomerular podocytes%Angiotensin-converting enzyme 2%Urinary albumin excretion rate
目的 探讨糖尿病大鼠肾组织局部血管紧张素转换酶(ACE)2对肾小球足细胞的影响及厄贝沙坦的干预作用.方法 56只Wistar大鼠经链脲佐菌素诱导糖尿病模型,死亡9只,其余随机分为糖尿病组(n=11)、30 mg/(kg·d)肼屈嗪干预组(n=9)、25 mg/(kg·d)厄贝沙坦干预组(n=9)、50 mg/(kg·d)厄贝沙坦干预组(n=9)、200 mg/(kg·d)厄贝沙坦干预组(n=9),同时设正常对照组(n=7).于造模后第4周开始予肼屈嗪、厄贝沙坦干预,第12周观察24h尿微量白蛋白排泄率(UAER),采用免疫组化技术检测肾组织ACE2的分布和表达情况,免疫组化SP法检测肾小球WT1表达情况,Image.Pro Plus 6.0彩色图像分析系统半定量检测足细胞密度.结果 正常对照组UAER低于糖尿病组和药物干预组[包括肼屈嗪干预组、25 mg/(kg·d)厄贝沙坦干预组、50 mg/(kg·d)厄贝沙坦干预组、200 mg/(kg·d)厄贝沙坦干预组](P＜0.001)；药物干预组UAER低于糖尿病组(P＜0.001)；所有厄贝沙坦干预组UAER较肼屈嗪干预组显著降低(P ＜0.05)；50 mg/(kg·d)厄贝沙坦干预组、200 mg/(kg·d)厄贝沙坦干预组UAER较25 mg/(kg·d)厄贝沙坦干预组明显降低(P＜0.001).肾组织ACE2表达与肾小球足细胞密度呈正相关(r=0.381,P＜0.001),糖尿病组ACE2表达较正常对照组明显降低(P＜0.05),而所有厄贝沙坦干预组显著高于糖尿病组和肼屈嗪干预组(P ＜0.001),厄贝沙坦干预组、肼屈嗪干预组足细胞密度显著高于糖尿病组(P ＜0.001)；200 mg/(kg·d)厄贝沙坦干预组高于肼屈嗪干预组、25 mg/(kg·d)厄贝沙坦干预组、50 mg/(kg·d)厄贝沙坦干预组、糖尿病组.结论 肾组织ACE2减少可导致足细胞密度降低,进而引起肾脏损害；而厄贝沙坦可上调肾组织ACE2的表达,增加足细胞密度,发挥降压外的肾脏保护作用,且呈现剂量依赖性.
目的 探討糖尿病大鼠腎組織跼部血管緊張素轉換酶(ACE)2對腎小毬足細胞的影響及阨貝沙坦的榦預作用.方法 56隻Wistar大鼠經鏈脲佐菌素誘導糖尿病模型,死亡9隻,其餘隨機分為糖尿病組(n=11)、30 mg/(kg·d)肼屈嗪榦預組(n=9)、25 mg/(kg·d)阨貝沙坦榦預組(n=9)、50 mg/(kg·d)阨貝沙坦榦預組(n=9)、200 mg/(kg·d)阨貝沙坦榦預組(n=9),同時設正常對照組(n=7).于造模後第4週開始予肼屈嗪、阨貝沙坦榦預,第12週觀察24h尿微量白蛋白排洩率(UAER),採用免疫組化技術檢測腎組織ACE2的分佈和錶達情況,免疫組化SP法檢測腎小毬WT1錶達情況,Image.Pro Plus 6.0綵色圖像分析繫統半定量檢測足細胞密度.結果 正常對照組UAER低于糖尿病組和藥物榦預組[包括肼屈嗪榦預組、25 mg/(kg·d)阨貝沙坦榦預組、50 mg/(kg·d)阨貝沙坦榦預組、200 mg/(kg·d)阨貝沙坦榦預組](P＜0.001)；藥物榦預組UAER低于糖尿病組(P＜0.001)；所有阨貝沙坦榦預組UAER較肼屈嗪榦預組顯著降低(P ＜0.05)；50 mg/(kg·d)阨貝沙坦榦預組、200 mg/(kg·d)阨貝沙坦榦預組UAER較25 mg/(kg·d)阨貝沙坦榦預組明顯降低(P＜0.001).腎組織ACE2錶達與腎小毬足細胞密度呈正相關(r=0.381,P＜0.001),糖尿病組ACE2錶達較正常對照組明顯降低(P＜0.05),而所有阨貝沙坦榦預組顯著高于糖尿病組和肼屈嗪榦預組(P ＜0.001),阨貝沙坦榦預組、肼屈嗪榦預組足細胞密度顯著高于糖尿病組(P ＜0.001)；200 mg/(kg·d)阨貝沙坦榦預組高于肼屈嗪榦預組、25 mg/(kg·d)阨貝沙坦榦預組、50 mg/(kg·d)阨貝沙坦榦預組、糖尿病組.結論 腎組織ACE2減少可導緻足細胞密度降低,進而引起腎髒損害；而阨貝沙坦可上調腎組織ACE2的錶達,增加足細胞密度,髮揮降壓外的腎髒保護作用,且呈現劑量依賴性.
목적 탐토당뇨병대서신조직국부혈관긴장소전환매(ACE)2대신소구족세포적영향급액패사탄적간예작용.방법 56지Wistar대서경련뇨좌균소유도당뇨병모형,사망9지,기여수궤분위당뇨병조(n=11)、30 mg/(kg·d)정굴진간예조(n=9)、25 mg/(kg·d)액패사탄간예조(n=9)、50 mg/(kg·d)액패사탄간예조(n=9)、200 mg/(kg·d)액패사탄간예조(n=9),동시설정상대조조(n=7).우조모후제4주개시여정굴진、액패사탄간예,제12주관찰24h뇨미량백단백배설솔(UAER),채용면역조화기술검측신조직ACE2적분포화표체정황,면역조화SP법검측신소구WT1표체정황,Image.Pro Plus 6.0채색도상분석계통반정량검측족세포밀도.결과 정상대조조UAER저우당뇨병조화약물간예조[포괄정굴진간예조、25 mg/(kg·d)액패사탄간예조、50 mg/(kg·d)액패사탄간예조、200 mg/(kg·d)액패사탄간예조](P＜0.001)；약물간예조UAER저우당뇨병조(P＜0.001)；소유액패사탄간예조UAER교정굴진간예조현저강저(P ＜0.05)；50 mg/(kg·d)액패사탄간예조、200 mg/(kg·d)액패사탄간예조UAER교25 mg/(kg·d)액패사탄간예조명현강저(P＜0.001).신조직ACE2표체여신소구족세포밀도정정상관(r=0.381,P＜0.001),당뇨병조ACE2표체교정상대조조명현강저(P＜0.05),이소유액패사탄간예조현저고우당뇨병조화정굴진간예조(P ＜0.001),액패사탄간예조、정굴진간예조족세포밀도현저고우당뇨병조(P ＜0.001)；200 mg/(kg·d)액패사탄간예조고우정굴진간예조、25 mg/(kg·d)액패사탄간예조、50 mg/(kg·d)액패사탄간예조、당뇨병조.결론 신조직ACE2감소가도치족세포밀도강저,진이인기신장손해；이액패사탄가상조신조직ACE2적표체,증가족세포밀도,발휘강압외적신장보호작용,차정현제량의뢰성.
Objective To observe the effects of the renal local angiotensin-converting enzyme 2 (ACE2) expressions on glomerular podocytes in diabetic rat and the function of irbesartan.Methods Fifty-six Wistar rats were induced diabetes by streptozotocin,nine were dead.The others were randomly divided into diabetes group (n =11),hydralazine administrated group (n =9),25 mg · kg-1 · d-1 irbesartan administrated group(n =9),50 mg · kg-1 · d-1 irbesartan administrated group(n =9),and 200 mg · kg-1 · d-1irbesartan administrated group(n =9),meanwhile normal control group were established (n =7).Four weeks after modeling,rats were administered with hydralazine or irbesartan separately.In the 12th week,24 hour urinary albumin excretion rate(UEAR) was measured.The distribution and expression of ACE2 in renal tissue were detected by immunohistochemistry.The renal glomerulus WT1 expression was detected by streptavidinperosidase(SP).Podocytes density was detected by Image.Pro Plus 6.0.Results The UAER in normal control group was lower than that in diabetes group and all the drug intervention groups (including hydralazine administrated group,25 mg · kg-1 · d-1 irbesartan administrated group,50 mg · kg-1 · d-1irbesartan administrated group,and 200 mg · kg-1 · d-1 irbesartan administrated group) (P ＜0.001).The UAER in all the drug intervention groups were lower than that in diabetes group(P ＜0.001).And in all the irbesartan administrated groups UAER were lower than that in hydralazine administrated group (P ＜ 0.0 5).In 50 mg · kg-1 · d-1 irbesartan administrated group and 200 mg· kg-1 · d-1 irbesartan administrated group,UAER were lower than that in 50 mg · kg-1 · d-1 irbesartan administrated group (P ＜ 0.001).The level of renal ACE2 was positively correlated with podocytes density(r =0.381,P ＜ 0.001).And it was significantly lower in diabetes group than that in normal control group(P ＜0.05).In all the irbesartan administrated groups,the levels of ACE2 were significantly higher than that in diabetes group and hydralazine administrated group(P ＜ 0.001).Podocytes density in all the irbesartan administrated groups and hydralazine administrated group were significantly higher than that in diabetes group(P ＜0.001).Podocytes density in 200 mg · kg-1 · d-1 irbesartan administrated group was significantly higher than that in hydralazine administrated group,25 mg · kg-1 · d-1 irbesartan administrated group,and 50 mg · kg-1 · d-1 irbesartan administrated group.Conclusions The reduction of renal local ACE2 expressions leads to reduction of the podocytes,and kidney damage.Irbesartan upregulates renal local ACE2 expressions and increases podocytes density.Irbesartan protects the kidney in dose-dependent manner,besides lowering blood pressure.
