血管紧张素受体拮抗剂对应用生长激素之阿霉素肾病大鼠的肾保护作用

目的　探讨生长激素 (GH)对阿霉素肾病大鼠肾损伤的影响及作用机制 ,同时研究血管紧张素受体拮抗剂对应用GH的阿霉素肾病大鼠的肾保护作用。方法　建立阿霉素肾病大鼠模型。将实验动物分为正常对照组、模型组 (阿霉素肾病 )、GH组 (阿霉素肾病 +GH)、伊贝沙坦组 (阿霉素肾病 +GH +伊贝沙坦 )。检测各组第 3、6、9周末的 2 4h蛋白尿。第 9周末检测血压、血白蛋白、甘油三酯、总胆固醇酯、尿素氮、肌酐 ,肾组织血管紧张素转化酶 (ACE)活性和血管紧张素Ⅱ (AngⅡ )浓度。观察肾脏病理损害情况。免疫组化法测定肾内转化生长因子 β1(TGFβ1)、Ⅳ型胶原 (colⅣ )、纤维连接蛋白 (FN)的蛋白表达水平。结果　GH组的肾小球硬化指数 (49 4± 9 8)明显高于模型组 (12 8± 5 5 ) (P <0 0 1) ,而伊贝沙坦组 (2 6 2± 7 5 )则低于GH组 (P <0 0 1)。各组间 2 4h蛋白尿 ,高脂血症 ,低蛋白血症的指标变化与肾脏损伤程度一致。GH组还出现明显的氮质血症 ,而其余 3组无氮质血症。GH组和伊贝沙坦组的肾组织ACE活性 [(2 8 1± 4 1)U/mg蛋白 ;(2 7 6± 3 4 )U/mg蛋白 ]、AngⅡ浓度 [(17 8± 3 3)pg/mg蛋白 ;(2 7 3± 5 1)pg/mg蛋白 ]明显高于模型组 [(14 6± 4 4 )U/mg蛋白 ;(8 3± 1 9)pg/mg蛋白 ](P <0 0 1)。免

Renal protective effect of angiotensin II receptor antagonist on growth hormone-treated nephrotic rats

OBJECTIVE: Children with nephrotic syndrome are always associated with retardation of growth. Growth hormone (GH) administration to these children can stimulate their growth, but it plays an important role in glomerulosclerosis. Thus these children would take a risk to use it to improve their growth. This study was designed to investigate the effect of GH on the kidney of rats with adriamycin-induced nephropathy (AN) and its mechanism, and to observe the renoprotective effect of angiotensin II (AngII) receptor antagonist, irbesartan, in GH-treated AN rats. METHODS: Rats were divided into the following groups: normal control rats, AN rats, GH-treated AN rats and GH plus irbesartan-treated AN rats. There were 8 developing male SD rats (120-130 g) in each group. Urinary protein was measured at weeks 3, 6 and 9. Blood pressure, serum creatinine, BUN, albumin, cholesterol, triglyceride, as well as ACE activity and AngII concentration of the kidney were detected at the end of the study. Renal pathological changes were evaluated also. Immunohistochemistry was used to examine the protein expressions of TGF beta(1), collagen IV and fibronectin in glomeruli. RESULTS: Glomerular sclerosis score of GH-treated AN rats (49.4 +/- 9.8) was significantly higher than that of AN rats (12.8 +/- 5.5, P < 0.01), and this score of GH-treated AN rats plus irbesartan (26.2 +/- 7.5) was significantly lower than the score of GH-treated AN rats (P < 0.01). The changes of urinary protein, hyperlipidemia and hypoalbuminemia in rats of each group consisted with the degree of glomerular injury in rats of each group. There was azotemia in GH-treated AN rats, but rats in the other groups did not have azotemia. ACE activity of kidney was significantly (P < 0.01) increased in GH-treated AN rats [(28.1 +/- 4.1) U/mg pro] and GH-treated AN rats plus irbesartan [(27.6 +/- 3.4) U/mg pro] compared with that in AN rats [(14.6 +/- 4.4) U/mg pro]. AngII concentrations in the kidney of GH-treated AN rats [(17.8 +/- 3.3) pg/mg pro] and GH-treated AN rats plus irbesartan [(27.3 +/- 5.1) pg/mg pro] were significantly higher than that in AN rats [(8.3 +/- 1.9) pg/mg pro] (P < 0.01). The protein expressions of TGF-beta(1), collagen IV and fibronectin in GH-treated AN rats were the most distinct in all groups. These expressions were significantly (P < 0.05) reduced in GH-treated AN rats plus irbesartan. CONCLUSION: GH is able to exacerbate adriamycin-induced nephropathy in rats, which was partly through activating renal tissue RAS and initiating the function of the AngII-TGF beta(1)-ECM axis. Angiotensin II receptor antagonist, irbesartan, has some renal protective effects on AN rats treated with GH.