阻断肾素-血管紧张素系统对糖尿病大鼠肾脏蛋白激酶C活性的影响  

Effects of blocking renin-angiotensin system on protein kinase C activity in diabetic rat kidney

作　　者：苏青[1] 董艳[1] 冯绮文[1] 宋小君[1] 邢惠莉[1] 左静南[1] 

机构地区：[1]上海第二医科大学附属新华医院内分泌科,200092

出　　处：《中华内分泌代谢杂志》2003年第2期133-135,共3页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的　观察阻断肾素 血管紧张素系统对糖尿病大鼠肾组织蛋白激酶C(PKC)活性的影响。方法　以链脲佐菌素造成大鼠糖尿病模型。未给予链脲佐菌素的大鼠作为正常对照组 (A组 ) ,糖尿病大鼠分为未处理组 (B组 )、福辛普利治疗组 (C组 )、洛沙坦治疗组 (D组 )和福辛普利 洛沙坦联合治疗组 (E组 )。 2 4周后测血糖、HbA1c、肾重 /体重、尿蛋白排泄率 (UPER)及肾组织PKC活性。结果　 ( 1)B组的肾重 /体重和UPER显著高于其余各组 ,C组和D组之间差异无显著性 ,E组较C组和D组更低 (P <0 .0 5 )。 ( 2 )B组肾组织膜PKC活性显著高于A组 (P <0 .0 0 1)、C组、D组和E组 (P <0 .0 1) ;B组胞液PKC活性显著低于A组(P <0 .0 1)、C组、D组和E组 (P <0 .0 5 ) ;B组胞液和膜PKC活性比显著低于A组 (P <0 .0 0 1)、C组、D组和E组 (P <0 .0 1)。C组和D组胞液PKC活性、膜PKC活性及二者之比差异无显著性 ,但E组的变化较C组和D组更为显著 (P <0 .0 5 )。结论　 ( 1)血管紧张素转化酶抑制剂 (ACEI)和血管紧张素Ⅱ受体拮抗剂(ARB)均能减轻糖尿病大鼠的肾脏肥大 ,减少UPER。 ( 2 )长期高糖可引起大鼠肾脏PKC活性异常升高并诱导胞液PKC向细胞膜转位。 ( 3 )ACEI和ARB均可抑制糖尿病大鼠肾脏PKC活性的升高及转位 ,二者的作用相当 。Objective To investigate the effects of blocking renin-angiotensin system on protein kinase C (PKC) activity in diabetic rat kidney. Methods Diabetic model of rats was induced by streptozotocin. Normal rats (group A) were provided as controls. The diabetic rats were divided into four groups: untreated diabetic control rats (group B), diabetic rats treated with Fosilopril (group C), diabetic rats treated with Losartan (group D), and diabetic rats treated with Fosilopril and Losartan (group E). Blood glucose, ratio of kidney weight to body weight (K/B), HbA 1c , urinary protein excretion rate (UPER) and PKC activity in kidney were measured after 24 weeks of treatment. Results (1) K/B and UPER in group B were higher than those in other groups. K/B and UPER in group E were lower than those in group C and D (P<0.05), but no significant difference was found between group C and group D; (2) Membrane PKC activity of kidney tissue in group B was higher than that in group A (P<0.001), group C, group D and group E (P<0.01). Cytosolic PKC activity in group B was lower than that in group A (P<0.01), group C, group D and group E (P<0.05). Ratio of PKC activities in cytosol fraction to that in membrane fraction in group B was lower than that in group A (P<0.001), group C, group D and group E (P<0.01). Membrane PKC activitiy in group E was lower than that in group C and D, cytosolic PKC activity and ratio of PKC activities in cytosol fraction to that in membrane fraction in group E were higher than that in group C and D (P<0.05), but no significant difference was found between group C and group D. Conclusion (1) Angiotension-converting enzyme inhibitor (ACEI) and angiotension Ⅱ receptor blocker (ARB) can ameliorate renal hypertrophy and UPER in diabetic rats. (2) Long-term hyperglycemia can activate PKC in diabetic kidney and induce translocation of PKC from cytosol to membrane. (3) ACEI and ARB have equivalent inhibitory effects on activation and translocation of PKC in diabetic rat kidney, and combined treatment with

关 键 词：肾素-血管紧张素系统 大鼠 蛋白激酶C活性 糖尿病肾病 并发症 

分 类 号：R587.1[医药卫生—内分泌]