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目的探讨雷米普利对糖尿病肾病(DN)大鼠胰岛素样生长因子-1(IGF-1)表达及肾系膜基质聚集的影响。方法 SD大鼠分为健康对照组(NC组,n=12)、DN组(n=11)、DN雷米普利干预组(DN+RAM组,n=12),腹腔注射链脲佐菌素构建DN模型,DN+RAM组予雷米普利3 mg·kg-1·d-1灌胃8周,检测肾重/体质量、空腹血糖(FBG)、糖化血红蛋白(Hb A1c)、24 h尿蛋白、血尿素氮、血肌酐;HE染色和电镜观察肾脏病理改变;免疫组织化学检测肾组织IGF-1表达;Western blot检测IGF-1、纤维连接蛋白(FN)、IV型胶原(Col-IV)和基质金属蛋白酶(MMP)-2表达。结果与NC组比较,DN组大鼠肾重/体质量、FBG、Hb A1c、24h尿蛋白、血尿素氮、血肌酐明显升高,肾小球肥大和系膜基质聚集明显,IGF-1、FN和Col-IV蛋白表达明显增加,MMP-2表达明显降低(P<0.05)。与DN组比较,DN+RAM组上述指标除FBG和Hb A1c外均明显改善(P<0.05)。IGF-1蛋白表达与24 h尿蛋白定量(r=0.937)、FN(r=0.896)和Col-IV(r=0.871)表达呈显著正相关,与MMP-2(r=-0.826)呈显著负相关(P<0.05)。结论雷米普利可通过抑制IGF-1的表达,减轻肾系膜基质聚集,发挥肾脏保护作用。
Objective To investigate the effect of ramipril on the expression of insulin-like growth factor-1 (IGF-1) and mesangial matrix in rats with diabetic nephropathy (DN). Methods SD rats were divided into healthy control group (NC group, n = 12), DN group (n = 11), DN ramipril intervention group (DN + RAM group, n = 12) The DN model was established. The rats in DN + RAM group were treated with ramipril 3 mg · kg-1 · d-1 for 8 weeks, and the renal weight / body weight, fasting blood glucose (FBG), Hb A1c, 24 h urinary protein, blood urea nitrogen and serum creatinine; the pathological changes of kidney were observed by HE staining and electron microscope; the expression of IGF-1 in renal tissue was detected by immunohistochemistry; the expressions of IGF-1, FN and Col -IV) and matrix metalloproteinase (MMP) -2 expression. Results Compared with NC group, the renal weight / body weight, FBG, Hb A1c, 24h urinary protein, blood urea nitrogen, serum creatinine in DN group were significantly increased, glomerular hypertrophy and mesangial matrix accumulation were obvious, FN and Col-IV protein expression increased significantly, MMP-2 expression was significantly reduced (P <0.05). Compared with DN group, the above indexes in DN + RAM group were significantly improved except FBG and Hb A1c (P <0.05). The expression of IGF-1 was positively correlated with the expression of 24 h urinary protein (r = 0.937), FN (r = 0.896) and Col-IV (r = 0.871) Negative correlation (P <0.05). Conclusion Ramipril can play a protective role in kidney by inhibiting the expression of IGF-1, reducing the aggregation of mesangial matrix.