Li Shuang, Cao Bin, Feng Qi-hua, Li Xiao-zhong
Department of Nephrology, Suzhou Children's Hospital, Suzhou University, Suzhou 215000 China.
Zhonghua Er Ke Za Zhi. 2003 Nov;41(11):817-21.
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.
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.
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.
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.
肾病综合征患儿常伴有生长发育迟缓。对这些患儿使用生长激素（GH）可刺激其生长，但生长激素在肾小球硬化中起重要作用。因此，这些患儿使用生长激素来改善生长存在风险。本研究旨在探讨生长激素对阿霉素诱导的肾病（AN）大鼠肾脏的影响及其机制，并观察血管紧张素II（AngII）受体拮抗剂厄贝沙坦对生长激素治疗的AN大鼠的肾脏保护作用。
将大鼠分为以下几组：正常对照大鼠、AN大鼠、生长激素治疗的AN大鼠和生长激素加厄贝沙坦治疗的AN大鼠。每组有8只发育中的雄性SD大鼠（120 - 130 g）。在第3、6和9周测量尿蛋白。在研究结束时检测血压、血清肌酐、尿素氮、白蛋白、胆固醇、甘油三酯以及肾脏的ACE活性和AngII浓度。同时评估肾脏病理变化。采用免疫组织化学法检测肾小球中转化生长因子β1（TGFβ1）、IV型胶原和纤连蛋白的蛋白表达。
生长激素治疗的AN大鼠的肾小球硬化评分（49.4±9.8）显著高于AN大鼠（12.8±5.5，P<0.01），生长激素治疗的AN大鼠加厄贝沙坦组的该评分（26.2±7.5）显著低于生长激素治疗的AN大鼠组（P<0.01）。每组大鼠的尿蛋白、高脂血症和低白蛋白血症的变化与每组大鼠的肾小球损伤程度一致。生长激素治疗的AN大鼠出现氮质血症，而其他组大鼠未出现氮质血症。与AN大鼠组[（14.6±4.4）U/mg pro]相比，生长激素治疗的AN大鼠组[（28.1±4.1）U/mg pro]和生长激素治疗的AN大鼠加厄贝沙坦组[（27.6±3.4）U/mg pro]的肾脏ACE活性显著升高（P<0.01）。生长激素治疗的AN大鼠组[（17.8±3.3）pg/mg pro]和生长激素治疗的AN大鼠加厄贝沙坦组[（27.3±5.1）pg/mg pro]的肾脏AngII浓度显著高于AN大鼠组[（8.3±1.9）pg/mg pro]（P<0.01）。生长激素治疗的AN大鼠中TGF-β1、IV型胶原和纤连蛋白的蛋白表达在所有组中最为明显。在生长激素治疗的AN大鼠加厄贝沙坦组中，这些表达显著降低（P<0.05）。
生长激素能够加重阿霉素诱导的大鼠肾病，这部分是通过激活肾组织肾素 - 血管紧张素系统（RAS）并启动AngII - TGFβ1 - 细胞外基质（ECM）轴的功能实现的。血管紧张素II受体拮抗剂厄贝沙坦对生长激素治疗的AN大鼠具有一定的肾脏保护作用。
