福辛普利和氯沙坦对糖尿病大鼠尿TGF-β_1排泄的影响

Effects of fosinopril and losartan on urinary TGFβ_1 excretion in diabetic rats

目的观察血管紧张素转换酶抑制剂(ACEI)-福辛普利和血管紧张素Ⅱ受体拮抗剂(ARB)-氯沙坦对糖尿病大鼠尿TGF-β1排泄的影响及其对肾小球病变保护的可能机制。方法建立糖尿病大鼠模型,分为正常对照(A组)、糖尿病组(B组)、福辛普利治疗组(C组)、氯沙坦治疗组(D组),每组各2只,C,D两组在模型建立一周后分别以福辛普利(5 mg/kg.d)、氯沙坦(10 mg/kg.d)灌胃给药。检测各组第1,2,4,12周血糖、24小时尿视黄醇结合蛋白(RBP)、尿TGFβ1排泄率以及尿白蛋白(Alb)排泄率,进行组间差异比较并分析各指标之间的相关性。结果(1)第1周(未用药)B,C,D组尿Alb排泄率与A组无统计学差异(P>0.05),但三组糖尿病大鼠尿RBP,TGFβ1排泄率均高于A组(P<0.05;P<0.01),尤其以TGFβ1排泄率升高最为显著;(2)第2,4,12周尿Alb,RBP,排泄率B组均显著高于A组(P<0.01),并随病程的延长不断增高,C,D组则较B组明显减少;(3)尿TGFβ1排泄率与尿Alb及RBP排泄率呈正相关(r=0.884,P<0.01;r=0.942,P<0.01)。结论ACEI和ARB可降低糖尿病大鼠尿TGFβ1的排泄,其保护糖尿病肾脏的机制部分可能与其下调肾组织TGFβ1的过度表达有关。

Objective To observe the effects of angiotensin converting enzyme inhibitor（ACEI） - fosinopril and angiotensin Ⅱ receptor blocker（AKB） - losartan on urinary TGFβ1 excretion in diabetic rats and explore their renoprotective mechanism.Methods Four groups of rats were studied： A group（ n = 12）, normal control rats; B group（ n = 12）, streptozotocin induced diabetic rats; C group （ n = 12） ,diabetic rats treated with fosinopril（5 mg/kg.d） ;D group （ n = 5）, diabetic rats treated with losartan （ 10 mg/kg. d） .Blood glucose,urinary albumin, TGFβ1 and retinal- binding protein（RBP） were measured at the 1 st,2nd,4th and 12th weeks. Results （ 1 ）At the 1 st week（no treatment given）, the urinary excretion rates of albumin in B, C, D groups were similar to that in A group （ P 〉 0.05 ）, but the urinary excretion rates of RBP and TGFβ1 were significant higher than those in A group; （2）At the 2nd, 4th andl2th week, the urinary excretion rates of albumin , RBP, TGFβ1 all increased in B group compared with those in A group （ P 〈 0.01 ）, and rose further with time. And in C, D group, the urinary excretion rates of the three proteins also increased compared with those in A group （ P 〈 0.01 ） ,but decreased significantly compared with those in B group（ P 〈 0.01 ） ,and no difference between C, D groups; （3）Urinary TGFβ1 excretion rate had positive relationship with the urinary Alb, RBP excretion rates （r= 0.884, P 〈 0.01 ; r = 0.942, P 〈 0.01, respectively）. Conclusion ACEI - Fosinopril and ARB - losartan can decrease urinary TGFβ1 excretion of diabetic rats, and their renoprotection may be partly due to their effects in down - regulating the TGFβl production in renal tissue.