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引用本文:包自阳,朱彩凤,李建秋,朱斌.缬沙坦对IgA肾病大鼠血清IgA1异常糖基化的影响[J].中国现代应用药学,2014,31(3):274-278.
BAO Ziyang,ZHU Caifeng,LI Jianqiu,ZHU Bin.Effects of Valsartan on Abnormal Glycosylation of Serum IgA1 in Rats with IgA Nephropathy[J].Chin J Mod Appl Pharm(中国现代应用药学),2014,31(3):274-278.
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缬沙坦对IgA肾病大鼠血清IgA1异常糖基化的影响
包自阳1, 朱彩凤1, 李建秋2, 朱斌1
1.杭州市中医院,杭州 310007;2.温岭市中医院肾内科,浙江 温岭 317500
摘要:
目的 观察IgA肾病(IgAN)大鼠血清IgA1异常糖基化的程度及缬沙坦对其影响。方法 将♂SD大鼠随机分为正常对照组、IgAN组、缬沙坦组、泼尼松组,每组12只。采用口服牛血清白蛋白(BSA)和尾静脉注射BSA和葡萄球菌肠毒素(SEB)的方法建立IgAN大鼠模型,缬沙坦组给予缬沙坦30 mg·kg-1·d-1,泼尼松组给予泼尼松5 mg·kg-1·d-1,灌胃给药。分别于1,8,12周测24 h尿蛋白量;12周处死大鼠取血,ELISA法测血清IgA含量,凝集素亲和ELISA法检测血清IgA异常糖基化的程度;肾组织切片观察病理学改变。结果 造模8周后IgAN组、缬沙坦组、泼尼松组大鼠尿蛋白较正常对照组显著增多,第12周时缬沙坦组及泼尼松组尿蛋白较IgAN组显著减少。IgAN组血清IgA水平较正常对照组显著升高,缬沙坦组及泼尼松组均较IgAN组显著减少。IgAN组大鼠光镜下肾系膜基质增生,系膜细胞增多,部分毛细血管攀闭塞;荧光下IgA呈团块状在系膜区沉积;缬沙坦组及泼尼松组病理较IgAN组显著改善,正常对照组未见病理改变。IgAN组IgA异常糖基化程度最重,缬沙坦组较IgAN组显著改善,泼尼松组无明显改善。结论 缬沙坦能显著降低血清IgA的水平,改善血清IgA1异常糖基化程度,改善临床及病理损伤。可见改善IgA1异常糖基化程度可能是缬沙坦治疗IgAN的重要机制之一。
关键词:  缬沙坦  IgA肾病  免疫球蛋白A  糖基化缺陷
DOI:
分类号:R692.3;
基金项目:杭州市医药卫生科技计划项目(2008A022)
Effects of Valsartan on Abnormal Glycosylation of Serum IgA1 in Rats with IgA Nephropathy
BAO Ziyang1, ZHU Caifeng1, LI Jianqiu2, ZHU Bin1
1.Traditional Chinese Medicine Hospital of Hangzhou, Hangzhou 310007, China;2.Traditional Chinese Medicine Hospital of Wenling, Wenling 317500, China
Abstract:
OBJECTIVE To investigate the effect of valsartan on abnormal glycosylation of serum IgA1 in rats with IgA nephropathy(IgAN). METHODS SD rats were randomly divided into normal group, IgAN group, valsartan group, and prednisone group, with 12 rats in each group. IgAN rats induced by oral administration of bovine serum albumin(BSA) and intravenous staphyloentero-Toxin (SEB) by turns. The valsartan group were treated by oral valsartan 30 mg·kg-1·d-1 and prednisone group by oral pred 5 mg·kg-1·d-1. The 24 h urinary protein excretion(UPE) were measured in the first, 8th, 12th week respectively. Rats were sacrificed at 12th week. Serum IgA was measured with ELISA method and abnormal glycosylated IgA was measured with lectin affinity ELISA method. The kidney sections by kinds of staining were observed for renal pathological change of the rats in each group. RESULTS Compared with normal group at 8th week, UPE increased significantly in IgAN group, valsartan group and prednisone group. UPE decreased significantly in valsartarn group and prednisone group compared with IgAN group at 12th week. The serum IgA in valsartan group and prednisone group decreased significantly compared with IgA group. Pathological injury such as glomerular capillary occlusion, increased mesangial matrix, mesangial cell proliferating, IgA deposition and electron-dense deposits in mesangial area were mitigated in valsartan group and prednisone group compared with IgAN group. Compared with normal group abnormal glycosylated IgA1 increased significantly in IgAN group but were extenuated in valsartan group. Abnormal glycosylated IgA were not ameliorated in prednisone group with respect to IgAN group. CONCLUSION Valsartan can decrease serum IgA and ameliorate abnormal glycosylation of IgA to improve the outcome of IgAN. It may be an important mechanism of valsartan to treat IgA nephropathy.
Key words:  valsartan  IgA nephropathy  immunoglobulin A  deglycosylation
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