摘要
目的研究1,25-(OH)2D3对糖尿病(DM)模型大鼠肾素-血管紧张肽-醛甾酮系统(RAAS)活性的影响及对肾小球足细胞的保护作用。方法将40只SD大鼠分为正常对照组(A组)、糖尿病组(B组)、血管紧张肽Ⅱ(AngⅡ)灌注组(C组)、AngⅡ+1,25-(OH)2D3灌注组(D组)。B、C、D组均腹腔注射链脲菌素(STZ)制作DM大鼠模型。C组皮下埋置渗透性微量泵,给予AngⅡ400ng·kg-1·min-1;D组经两条渗透性微量泵通路分别给予AngⅡ(400ng·kg-1·min-1)+1,25-(OH)2D3(450ng·kg-1·min-1)。两组均连用10周。检测大鼠血糖(BG)、收缩压(SBP)、24h尿蛋白定量(TP)和肾素活性(PRA)、血管紧张肽Ⅱ(AngⅡ)和醛甾酮(Ald)水平。检测尿沉渣足细胞特异性标志蛋白podocalyxin以检测尿液足细胞(UPC)水平,免疫荧光染色观察肾小球上皮细胞蛋白-1(GLEPP1)的分布。结果B组BG、SBP、UPC、TP、PRA、AngⅡ、Ald均较A组明显升高。C组SBP、UPC、TP、PRA、AngⅡ、Ald较B组均明显升高(P<0.05或P<0.01)。D组SBP、UPC、TP、AngⅡ、Ald较C组明显降低,D组AngⅡ较B组明显降低。病理组织肾小球荧光染色示A组GLEPP1正常分布,C组呈明显缺失,B和D组亦缺失。UPC与TP、AngⅡ呈正相关(rs=0.51,0.35,P<0.01,P<0.05)。结论1,25-(OH)2D3可能是RAAS的负向调节因子,通过下调RAAS活性,防止足细胞脱落排泄介导其肾保护作用。
Objective To investigate the influence of 1,25-dihydroxyvitamin D3 [ 1,25-（OH）2D3 ] on the activation of the renin angiotensin aldosterone system（RAAS） in rats with diabetes mellitus （DM）, and the protection on podocyt. Methods SD rats were divided into four groups, normal control group（group A）, DM group（group B） , angiotensin Ⅱ （Ang Ⅱ ）group （ group C） , and Ang Ⅱ combined with 1,25- （OH）2O3 （ group D） group. DM rats were induced by i.p. streptozotocin （STZ）. Group C was embedded with the osmotic minipump for giving 400 ng·kg^-1·min^-1 Ang Ⅱ. Group D was given 400 ng·kg^-1·min^-1 AngⅡ and 450 ng · kg^-1·min^-1 1,25-（ OH）2 D3 by two osmotic minipumps. Blood glucose（BG）, contractive pressure（SBP） ,24 h total proteinuria （TP） ,the activation of renin, the level of Ang Ⅱ and aldosterone（Aid） were measured after 10 week＇s treatment. The podocalyxin（ PCX, podocyte-specific marker） was detected to identity the urinary podocytes（UPC） and the distribution of glomerular epithelial cell membrane protein-1 （ GLEPP1 ） was observed by jmmunofluorescene. Results BC,SBP, UPC, TP,PRA,AngⅡ and Aid in group B were significantly higher than those in group A. SBP, UPC,TP,PRA,Ang Ⅱ and Ahl in group C were significantly raised compared with those in group B （P 〈0.05 or P 〈0.01 ）. SBP, UPC ,TP,Ang Ⅱ and Aid in group D were significantly lower than those in group C. Ang Ⅱ in group D was significantly lower than that in group B. Histologically, the distribution of GLEPP1 in glomeruli was normal in group A by immunofluorescene, obviously absence in group C, and absence in group B and D. The positive correlations were found between the levels of UPC with TP（ r = 0.51,P 〈 0.01 ） and AngⅡ （r =0.35,P〈0.05）. Conclusion 1,25（OH）2D3 may be a negative regulator for the renin-angiotensin system by down-regulating the activity of RAAS to prevent the defluvium and excretion of podocyte, which mediating its renal protective effects.
出处
《医药导报》
CAS
2008年第5期530-533,共4页
Herald of Medicine
